Differing Effects of Aliskiren/Amlodipine Combination and High-Dose Amlodipine Monotherapy on Ambulatory Blood Pressure and Target Organ Protection.
Mizuno Hiroyuki,Hoshide Satoshi,Fukutomi Motoki,Kario Kazuomi
Journal of clinical hypertension (Greenwich, Conn.)
The aim of this study was to compare an aliskiren/amlodipine combination with high-dose amlodipine monotherapy on ambulatory blood pressure monitoring (ABPM) and organ protection. The study was a prospective, randomized, multicenter, open-label trial in elderly essential hypertensive patients. A total of 105 patients with clinic BP (CBP) ≥140/90 mm Hg with amlodipine 5 mg were randomly allocated to aliskiren (150-300 mg)/amlodipine (5 mg) (ALI/AML group, n=53) or high-dose amlodipine (10 mg) (h-dAML group, n=52) and treated for 16 weeks. Each patient's CBP, ABPM, urine albumin-to-creatinine ratio (UACR), and brachial-ankle pulse wave velocity (baPWV) were measured at baseline and at the end of the study. The ALI/AML and h-dAML groups showed similarly reduced mean 24-hour SBP, daytime SBP, nighttime SBP, and baPWV. However, UACR reduction was significantly greater in the ALI/AML group (P=.02). ALI/AML was significantly less effective in reducing early-morning BP (P=.002) and morning BP surge (P=.001) compared with h-dAML.
Effects of combining azilsartan medoxomil with amlodipine in patients with stage 2 hypertension.
Weber Michael A,White William B,Sica Domenic,Bakris George L,Cao Charlie,Roberts Andrew,Kupfer Stuart
Blood pressure monitoring
OBJECTIVE:The aim of the study was to measure the effects on blood pressure (BP) of the angiotensin receptor blocker azilsartan medoxomil, in 40 and 80 mg doses, combined with 5 mg of the calcium channel blocker amlodipine and to compare these effects with placebo plus amlodipine 5 mg. METHODS:This was a randomized, controlled, double-blind study of 6 weeks' duration in 566 patients with stage 2 hypertension. The primary endpoint was 24-h systolic BP by ambulatory monitoring. RESULTS:The mean age of the participants was 58 years; men and women were equally represented, and baseline 24-h BP (153-154/93 mmHg) and clinic BP (165-166/94-95 mmHg) were similar across the three treatment groups. After 6 weeks, 24-h BP decreased by 25/15 mmHg in both the azilsartan medoxomil/amlodipine 40/5 and 80/5 mg groups. These reductions were each greater than the 14/8 mmHg decrease with placebo plus amlodipine 5 mg (P≤0.001 for both comparisons). All treatments were well tolerated, and adverse events did not increase with the azilsartan medoxomil doses. Edema or fluid retention was less common in both combination groups (2.6 and 2.7%) than with placebo plus amlodipine (7.6%). CONCLUSION:Coadministration of azilsartan medoxomil with amlodipine was well tolerated and led to meaningful additional BP reductions compared with placebo plus amlodipine.
Efficacy and safety of olmesartan/amlodipine/hydrochlorothiazide in patients with hypertension not at goal with mono, dual or triple drug therapy: results of the CHAMPiOn study.
Punzi Henry A
Therapeutic advances in cardiovascular disease
OBJECTIVE:To assess the efficacy and safety of once daily olmesartan medoxomil (OM)/amlodipine besylate (AM)/hydrochlorothiazide (HCTZ) 40/10/25 mg in patients with hypertension not at goal with mono, dual or triple drug therapy. METHODS:This was a single-center, prospective, open-label, blinded-endpoint study. After a 1-week screening visit, 40 patients were enrolled into the study and given once daily treatment with OM/AM/HCTZ after the patients underwent baseline ambulatory blood pressure monitoring (ABPM) on their original therapy. The primary endpoint was changes from baseline in mean 24 h ABPM [systolic blood pressure (SBP)] after the first day of therapy with OM/AM/HCTZ 40/10/25 mg. Secondary endpoints were changes from baseline in mean 24 h ABPM [diastolic blood pressure (DBP)] after the first day of therapy with OM/AM/HCTZ 40/10/25 mg; mean changes from baseline in trough seated SBP (SeSBP) at day 1 and SeSBP at weeks 1, 2, 3 and 4; mean changes from baseline in trough seated DBP (SeDBP) at day 1 and SeDBP at weeks 1, 2, 3 and 4; and the percentage of subjects achieving mean 24 h, daytime and night-time ABPM BP goals. RESULTS:The baseline paired t-test systolic ABPM was 134.0 ± 2.77 mmHg and day 1 was 128.6 ± 2.47 mmHg with a treatment difference of -5.55 ± 1.3 mmHg (p<0.0001). At week 1, paired t-test ABPM SBP reduction was 117.7 ± 2.0 mmHg with a treatment difference of -16.5 ± 1.8 mmHg (p < 0.0001). At week 2, paired t-test ABPM SBP reduction was 115.8 ± 1.8 mmHg with a treatment difference of -18.4 ± 2.0 mmHg (p < 0.0001). At week 3, paired t-test ABPM SBP reduction was 115.5 ± 1.9 mmHg with a treatment difference of -18.6 ± 2.0 mmHg (p < 0.0001). At week 4, paired t-test ABPM SBP reduction was 115.5 ± 1.8 mmHg with a treatment difference of -18.6 ± 2.2 mmHg (p < 0.0001). The baseline paired t-test SeSBP was 142 ± 2.43 mmHg and day 1 was 132 ± 2.59 mmHg with a treatment difference of -9.78 ± 1.51 mmHg (p < 0.0001). At week 1, paired t-test SeSBP reduction was 124.0 ± 1.6 mmHg with a treatment difference of -17.9 ± 1.8 mmHg (p < 0.0001). At week 2, paired t-test SeSBP reduction was 120.3 ± 1.7 mmHg with a treatment difference of -21.5 ± 2.1 mmHg (p < 0.0001). At week 3, paired t-test SeSBP reduction was 118.5 ± 1.8 mmHg with a treatment difference of -23.3 ± 1.7 mmHg (p < 0.0001). At week 4, paired t-test SeSBP reduction was 119.6 ± 1.7 mmHg with a treatment difference of -22.2 ± 1.9 mmHg (p < 0.0001). CONCLUSION:Treatment with OM/AM/HCTZ achieved superior (SBP) ABPM reductions compared with mono, dual or triple drug therapy, resulting in all patients achieving systolic ABPM goal without ABPM documented hypotension.
Impact of antihypertensive combination and monotreatments on blood pressure variability: assessment by old and new indices. Data from a large ambulatory blood pressure monitoring database.
Parati Gianfranco,Dolan Eamon,Ley Ludwin,Schumacher Helmut
Journal of hypertension
OBJECTIVES:High 24-h ambulatory blood pressure (ABP) variability is associated with poor cardiovascular outcomes. We analysed a large ABP monitoring database containing data from hypertensive patients treated with telmisartan/amlodipine combination or various monotherapies with the aim of quantifying the 24-h distribution of blood pressure (BP) reduction by treatment through the smoothness index and of developing and testing a new treatment-on-variability index (TOVI) to quantify the effects of treatment on both mean BP and BP variability. METHODS:ABP data were pooled from 10 studies (N = 4294) with a median follow-up of 60 days. Smoothness index was calculated by dividing the mean of treatment-induced hourly BP reductions by its SD. TOVI was calculated as the ratio of the mean of hourly BP reductions to weighted 24-h BP SD (weighted mean of daytime and night-time SDs) under treatment. RESULTS:The SBP/DBP smoothness index and TOVI values of telmisartan/amlodipine combination were significantly (P < 0.0001) higher (smoothness index: 1.81/1.51; TOVI: 2.71/2.13) compared with telmisartan 80 mg (smoothness index: 1.12/0.90; TOVI: 1.55/1.23), amlodipine 10 mg (smoothness index: 1.33/1.09; TOVI: 2.09/1.58), valsartan 160 mg (smoothness index: 1.01/0.81; TOVI: 1.35/1.07), ramipril 10 mg (smoothness index: 0.83/0.63; TOVI: 1.11/0.87) and placebo (smoothness index: 0.23/0.18; TOVI: 0.34/0.30), indicating a smoother 24-h BP reduction profile (higher smoothness index) as well as the achievement of significantly lower and smoother BP levels over 24 h (higher TOVI) with the combination. CONCLUSION:As compared with various monotherapies, the telmisartan/amlodipine combination was associated with a smoother BP reduction over 24 h and with a more favourable balance between mean 24-h BP reduction and the degree of BP variability on treatment, reflecting both its effectiveness in lowering BP levels and its longer duration of action. The agreement between smoothness index and TOVI demonstrates that they are similarly effective in the differentiation of antihypertensive treatments, although providing conceptually different information, the clinical relevance of which needs to be tested by ad-hoc outcome studies.
Adherence to oral antihypertensive medications, are all medications equal?
Shani Michal,Lustman Alex,Vinker Shlomo
Journal of clinical hypertension (Greenwich, Conn.)
Good medication adherence is a key factor in chronic disease management. Poor adherence is associated with adverse outcomes and high costs. We aimed to explore adherence rates among oral antihypertensive medications. The study included members of the Central District of Clalit Health Services in Israel aged between 40 and 75 years, who were diagnosed with hypertension before 2012 and who filled at least one prescription per year during 2012-2014, for the following medications: hydrochlorothiazide, nifedipine, amlodipine, lercanidipine hydrochloride, atenolol, bisoprolol, angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor antagonists (ARBs), and statins. Purchase of at least nine monthly prescriptions during 2013 was considered as "good medication adherence." We compared systolic blood pressure and LDL levels, according to medication adherence, for each medication and cross-adherence rates between medications. The study included 31 530 subjects. The rates of good medication adherence varied widely among the medications investigated, ranging from 53% for statins and hydrochlorothiazide to 71% for amlodipine. Mean systolic BP and LDL levels were statistically significantly lower among persons with good, compared to lower adherence, for each of the medications investigated. Both advanced age and more chronic medications were associated with higher adherence rates for all medications tested. Poor adherence to any single medication was found to be associated with lower adherence to other medications. Different antihypertensive medications have different adherence rates. Since adherence to one medication is related to adherence to other medications, investing in medication adherence may be highly beneficial.
Ambulatory Blood Pressures in Hypertensive Patients Treated With One Antihypertensive Agent: Differences Among Drug Classes and Among Drugs Belonging to the Same Class.
de la Sierra Alejandro,Gorostidi Manuel,Banegas José R,Segura Julián,Vinyoles Ernest,de la Cruz Juan J,Ruilope Luis M
Journal of clinical hypertension (Greenwich, Conn.)
The authors investigated the differences in office and ambulatory blood pressure (BP) among major antihypertensive drug classes and among frequently used drugs in each class in 22,617 patients treated with monotherapy from the Spanish ABPM Registry. Using thiazides as the reference group, patients treated with calcium channel blockers have significantly (P<.01) elevated ambulatory BP and less ambulatory control after adjusting for confounders. Inside each class, no significant differences were observed among thiazides or angiotensin receptor blockers. Atenolol and bisoprolol among β-blockers, amlodipine among calcium channel blockers, and lisinopril and enalapril among angiotensin-converting enzyme inhibitors exhibited lower ambulatory BP and better control than other agents. Differences exist among antihypertensive drug classes and among different compounds in each class with respect to ambulatory BP control. This can help physicians choose among drug classes and among compounds in each class if BP reduction is the main objective of treatment.
Effects of Celiprolol and Bisoprolol on Blood Pressure, Vascular Stiffness, and Baroreflex Sensitivity.
Eguchi Kazuo,Hoshide Satoshi,Kario Kazuomi
American journal of hypertension
BACKGROUND:We tested the hypothesis that celiprolol and bisoprolol have differential effects on blood pressure (BP), flow-mediated dilation (FMD), and vascular stiffness. METHODS:We analyzed 102 hypertensives (mean age: 59±14 years) who were being treated other than beta-blockers. They were randomized to receive add-on treatment with either celiprolol 100-200mg (C group) or bisoprolol 2.5-5mg (B group), and followed up for 3 months. In addition to clinic, home, and ambulatory BP monitoring, the FMD, radial augmentation index (AI), brachial-ankle pulse wave velocity (baPWV), urine albumin-to-creatinine ratio, and baroreflex sensitivity (BRS) were measured at baseline and at the end of the study. RESULTS:Compared to the baseline values, home and 24-hour BP were significantly lowered in the third month in both groups (all Ps < 0.05). Pulse rate (PR) and baPWV were reduced (P < 0.001), and BRS was increased significantly only in the B group (P = 0.02). Radial AI was unchanged in the C group but was significantly increased in the B group (P < 0.001). Central BP was significantly reduced in the C group (P = 0.003) but was unchanged in the B group. FMD was significantly increased in both groups (both P < 0.01). CONCLUSION:Bisoprolol achieved the greater reduction of PR and improved BRS and vascular stiffness, whereas, celiprolol reduced the central BP level. In treated hypertensive patients, add-on use of celiprolol may be favorable in uncomplicated stage of hypertension. On the other hand, bisoprolol may be useful in hypertensives with cardiac or vascular diseases who have advanced atherosclerotic changes and sympathetic nervous system activation.
Antihypertensive efficacy and safety of the angiotensin receptor blocker azilsartan in elderly patients with hypertension.
Kamada Tomohito,Hayashi Mutsuharu,Fujiwara Wakaya,Yoshikawa Daiji,Mukaide Daisuke,Sugishita Yoshinori,Yoshinaga Masataka,Itoh Takehiro,Yokoi Hiroatsu,Ishii Junichi,Watanabe Eiichi,Ozaki Yukio,Izawa Hideo
Drug and chemical toxicology
OBJECTIVES:The number of elderly patients with hypertension has been steadily increasing. However, there are limited data on the safety and efficacy of the new angiotensin type 1 receptor blocker (ARB) azilsartan in elderly patients with hypertension. We investigated the clinical efficacy and safety of azilsartan in this population. METHODS:The study population comprised 56 ambulatory patients with essential hypertension. We evaluated the reduction in blood pressure and safety after 12 weeks of treatment with azilsartan in 29 hypertensive patients ≥65 years of age (aged group) in comparison with the findings in 27 patients <65 years of age (non-aged group). RESULTS:Systolic blood pressure in the aged group declined significantly from 155 ± 18 mmHg at baseline to 138 ± 11 mmHg after 12 weeks of treatment with azilsartan, and that in the non-aged group also declined significantly from 152 ± 20 mmHg at baseline to 142 ± 13 mmHg after 12 weeks of treatment with azilsartan. There were no significant differences in the magnitude of change in blood pressures from pre-treatment to post-treatment with azilsartan between the non-aged and aged groups. There were no changes in clinical laboratory findings, including serum levels of creatinine, potassium, lipids, and other metabolic variables, after 12 weeks of treatment with azilsartan in both groups. CONCLUSIONS:Our findings suggest that azilsartan is effective in lowering blood pressure in elderly patients and may be safe. Therefore, azilsartan could be a valuable option for treating hypertension in elderly and non-elderly patients.
2020 Consensus summary on the management of hypertension in Asia from the HOPE Asia Network.
Kario Kazuomi,Park Sungha,Chia Yook-Chin,Sukonthasarn Apichard,Turana Yuda,Shin Jinho,Chen Chen-Huan,Buranakitjaroen Peera,Divinagracia Romeo,Nailes Jennifer,Hoshide Satoshi,Siddique Saulat,Sison Jorge,Soenarta Arieska Ann,Sogunuru Guru Prasad,Tay Jam Chin,Teo Boon Wee,Zhang Yu-Qing,Van Minh Huynh,Tomitani Naoko,Kabutoya Tomoyuki,Verma Narsingh,Wang Tzung-Dau,Wang Ji-Guang
Journal of clinical hypertension (Greenwich, Conn.)
Hypertension professionals from Asia have been meeting together for the last decade to discuss how to improve the management of hypertension. Based on these education and research activities, the Hypertension, brain, cardiovascular and renal Outcome Prevention and Evidence in Asia (HOPE Asia) Network was officially established in June 2018 and includes experts from 12 countries/regions across Asia. Among the numerous research and review papers published by members of the HOPE Asia Network since 2017, publications in three key areas provide important guidance on the management of hypertension in Asia. This article highlights key consensus documents, which relate to the Asian characteristics of hypertension, home blood pressure monitoring (HBPM), and ambulatory blood pressure monitoring (ABPM). Hypertension and hypertension-related diseases are common in Asia, and their characteristics differ from those in other populations. It is essential that these are taken into consideration to provide the best opportunity for achieving "perfect 24-hour blood pressure control", guided by out-of-office (home and ambulatory) blood pressure monitoring. These region-specific consensus documents should contribute to optimizing individual and population-based hypertension management strategies in Asian country. In addition, the HOPE Asia Network model provides a good example of the local interpretation, modification, and dissemination of international best practice to benefit specific populations.
Effects of Amlodipine and Valsartan on Blood Pressure Variability and Pulse Wave Velocity in Hypertensive Patients.
Shi Rufeng,Liu Kai,Shi Di,Liu Qi,Chen Xiaoping
The American journal of the medical sciences
OBJECTIVES:Antihypertensive therapy is effective to control blood pressure (BP) and to prevent cardiovascular events, but the further treatment strategies for patients who cannot achieve goal BP with low-dose monotherapy is still under dispute. Our study investigates the effects of high-dose amlodipine and valsartan and their low-dose combination on blood pressure variability (BPV) and pulse wave velocity (PWV) to provide references for clinical medication. MATERIALS AND METHODS:This study was a prospective, randomized, parallel, case-controlled trial performed in a medical center. A total of 134 outpatients newly diagnosed with essential hypertension or receiving low-dose monotherapy were enrolled and 119 completed the trial. They were randomized into amlodipine 10mg group (n = 40), valsartan 160mg group (n = 38) and amlodipine 5mg + valsartan 80mg (n = 41) in a 1:1:1 allocation ratio for a 10-week treatment. Demographic data and laboratory indicators were collected at the randomization and 10 weeks after the treatment. The 24-hour ambulatory BP and brachial-ankle PWV were also monitored. RESULTS:All therapies reduced systolic and diastolic BP (P < 0.05). The 24-hour systolic BPV was significantly decreased in amlodipine and combination groups (3.55 ± 2.57, 4.11 ± 2.20 versus 2.23 ± 2.54mmHg, P < 0.05). The effects on diastolic BPV differed between different treatments. PWV was lowered by 3 antihypertensive schemes; the degree of which from strongest to weakest were valsartan, combination and amlodipine (228.87 ± 60.41 versus 152.49 ± 49.25 versus 99.35 ± 35.57cm/second, P < 0.01). CONCLUSIONS:All further strategies can effectively control BP. The combination treatment reduces both BPV and PWV noticeably, whereas double-dose amlodipine achieves the greatest BPV decrease and valsartan is best in controlling PWV.
Ambulatory blood pressure monitoring in clinical practice.
Dadlani Apaar,Madan Kushal,Sawhney J P S
Indian heart journal
Being one of the most widely prevalent diseases throughout the world, hypertension has emerged as one of the leading causes of global premature morbidity and mortality. Hence, blood pressure (BP) measurements are essential for physicians in the diagnosis and management of hypertension. Current American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend initiating antihypertensive medications on the basis of office BP readings. However, office BP readings provide a snapshot evaluation of the patient's BP, which might not reflect patient's true BP, with the possibility of being falsely elevated or falsely low. Recently, there is ample evidence to show that ambulatory blood pressure monitoring (ABPM) is a better predictor of major cardiovascular events than BP measurements at clinic settings. ABPM helps in reducing the number of possible false readings, along with the added benefit of understanding the dynamic variability of BP. This article will focus on the significance of ambulatory BP, its advantages and limitations compared with the standard office BP measurement and a brief outlook on its use and interpretation to diagnose and treat hypertension.
24-Hour blood pressure response to lower dose (30 mg) fimasartan in Korean patients with mild to moderate essential hypertension.
Lee Hae-Young,Kim Cheol-Ho,Song Jae-Kwan,Chae Shung Chull,Jeong Myung Ho,Kim Dong-Soo,Oh Byung-Hee
The Korean journal of internal medicine
BACKGROUND/AIMS:Fimasartan is an angiotensin type 1 receptor blocker (ARB) which has comparable efficacy and tolerability with other ARBs. The aim of this study was to evaluate 24-hour blood pressure (BP) lowering efficacy and the tolerability of the low dose fimasartan compared with valsartan in patients with mild to moderate hypertension. METHODS:This study was a phase II, prospective, multicenter, randomized, double-blind, parallel-grouped trial. A total of 75 hypertensive patients, whose mean ambulatory BP monitoring values were ≥ 135/85 mmHg, were randomized to either fimasartan 30 mg or valsartan 80 mg daily. The primary efficacy endpoint was the change in the mean 24-hour systolic BP (SBP) values from the baseline and at the week 8. Secondary endpoints included the change in the mean 24-hour diastolic BP values, the daytime and the nighttime mean BP values at week 8, the trough-to-peak (T/P) ratio and the smoothness index. RESULTS:At week 8, the mean 24-hour SBP values significantly decreased in both groups; -10.5 ± 11.9 mmHg (p < 0.0001) in the fimasartan group and -5.5 ± 11.6 mmHg (p = 0.0307) in the valsartan group. The difference between two groups was 4.3 ± 2.9 mmHg but there was no statistical significance (p = 0.1392). The global T/P ratio in the fimasartan 30 mg groups were 0.48 and 0.40 in the valsartan 80 mg group, respectively (p = 0.3411). The most frequent adverse events (AEs) were acute pharyngitis and there were no cases of severe AEs. CONCLUSIONS:In mild-to-moderate hypertensive patients, low dose (30 mg) fimasartan showed comparable 24-hour BP lowering efficacy compared with valsartan (80 mg). There was no difference in tolerability between two groups.
[Ambulatory blood pressure monitoring for hypertension diagnosis?]
Gijón Conde T,Banegas J R
Hipertension y riesgo vascular
The early and accurate diagnosis of hypertension is essential given its importance in the development of cardiovascular disease. The boundaries between normal blood pressure (BP) and hypertension are arbitrary and based on the benefits of treating exceeding those of not treating. Conventional BP measurement at the clinic only offers information of a particular time and presents multiple biases dependent on inherent variability of BP and measurement technique itself. Multiple studies have demonstrated the prognosis superiority in the development of cardiovascular disease of ambulatory blood pressure monitoring (ABPM), allows detection of white coat hypertension, avoiding overdiagnosis and overtreatment, and the detection of patients with masked hypertension who are at risk of underdetection and undertreatment. ABPM also assess nightime BP and circadian variability, providing additional prognostic value. ABPM is recognized in the diagnosis of hypertension in 2011 British NICE Guidelines, very argued at the 2013 European Society of Hypertension guidelines, and recommended in the US Preventive Services Task Force in 2015, 2016 Canadian Guidelines and the 2016 Spanish Program of Preventive Activities and Health Promotion (PAPPS). Its generalization is likely to be only a matter of time.
Effects of Different Antihypertensive Drug Combinations on Blood Pressure and Arterial Stiffness.
Jatic Zaim,Skopljak Amira,Hebibovic Sevala,Sukalo Aziz,Rustempasic Edhem,Valjevac Amina
Medical archives (Sarajevo, Bosnia and Herzegovina)
Introduction:Hypertension is significantly contributing to global mortality and morbidity and has been identified as the most important modifiable risk factor for early development of cardiovascular diseases (CVD). Aim:The aim of this study was to investigate the efficacy of different combinations of antihypertensive therapy on blood pressure, arterial stiffness and peripheral resistance in patients with essential hypertension using the brachial oscillometric ambulatory blood pressure monitor. Methods:This study was designed as an observational, prospective, multi centric study conducted in eight primary care centers of the Health Center of Canton Sarajevo during the period of six months. The study included 655 participants, both genders, aged between 30 and 75, who were diagnosed with hypertension according to the ESC/ESH guidelines. Participants were divided into six treatment groups based on the hypertensive drug therapy they were using; lisinopril, losartan or valsartan alone or in combination with hydrochlorothiazide (A, B and C group respectively) or combination of lisinopril, losartan or valsartan with/without hydrochlorothiazide together with amlodipine (D, E and F respectively). The participants were monitored at baseline, after 3 and 6 months (1 and 2 follow-up). Brachial oscillometric ambulatory blood pressure monitor was used for measuring systolic (SBP), diastolic (DBP), pulse pressure (PP), pulse wave velocity (PWV) and peripheral resistance (PR). Results:SBP, DPB, PP, and PWV significantly decreased from baseline to 2 follow-up in all treatment groups. The mean reductions in SBP were from -11.7 (95%CI; 9.3- 14.1) to -23.2 (95%CI; 18.3-28.1) mmHg and DBP reductions varied from -5.5 (95%CI; 3.9- 7.1) to -13.4 (95%CI; 7.7-19.1) mmHg. PWV decreased in all treatment groups (from -3.3% to -8.2%). Treatment regiment was not associated with significant differences in SBP, DBP, PP or PWV reductions or their values measured at 2 follow-up. Peripheral resistance significantly decreased only in group C (p=0.011), group D (p=0.009) and group F (p=0.027). Conclusion:These data suggest that lisinopril/lisinopril + hydrochlorothiazide, losartan/losartan + hydrochlorothiazide and valsartan/valsartan + hydrochlorothiazide alone or in combination with amlodipine are equally effective and well tolerated for the reduction of both systolic and diastolic blood pressure and improve arterial stiffness in patients with essential hypertension.
Blood pressure-lowering efficacy and safety of perindopril/indapamide/amlodipine single-pill combination in patients with uncontrolled essential hypertension: a multicenter, randomized, double-blind, controlled trial.
Mourad Jean-Jacques,Amodeo Celso,de Champvallins Martine,Brzozowska-Villatte Romualda,Asmar Roland,
Journal of hypertension
OBJECTIVES:This 4-month, double-blind, randomized, controlled trial was designed to demonstrate the superiority of perindopril/indapamide/amlodipine single pill over perindopril/indapamide after 1 month and to determine further up-titration efficacy and safety in patients with mild-to-moderate hypertension. METHODS:After a 1-month run-in period on perindopril/indapamide 5/1.25 mg, patients with SBP/DBP at least 150/95 mmHg and no diabetes or renal insufficiency received perindopril/indapamide/amlodipine 5/1.25/5 mg single pill or continued on the same treatment. At 1, 2, and 3 months, patients with uncontrolled blood pressure (SBP/DBP ≥ 140/90 mmHg) were gradually up-titrated with a higher dose of the triple therapy up to perindopril/indapamide/amlodipine 10/2.5/10 mg in both groups. Efficacy was assessed on office supine SBP (main criterion) and DBP, blood pressure control, and response rates. Treatment effect on ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM) parameters was also assessed in two subpopulations of 276 and 263 patients, respectively. RESULTS:A total of 454 hypertensive patients (diabetes and renal insufficiency excluded) were randomized, 227 to each group (56% were men, mean age was 55 years, blood pressure 162.3/101.1 mmHg). After 1 month, superior SBP (-3.1 mmHg, P = 0.02) and DBP (-2.8 mmHg, P < 0.001) reductions were observed with perindopril/indapamide/amlodipine, which were even more pronounced after excluding white-coat effect in the sustained hypertension population (-5.3/-3.7 mmHg). Similar results were observed in terms of blood pressure response (72 vs. 53%, P < 0.0001) and control rates (32 vs. 25%, P = 0.005). Up-titration was effective at each visit in both treatment arms (P < 0.001). Both ABPM and HBPM results confirmed the superiority of the triple therapy at 1 month on ASBP/ADBP and HSBP/HDBP: -4.5/-2.0 mmHg for ABPM (P < 0.001/P = 0.04), and -4.9/-3.1 mmHg for HBPM (both, P < 0.001). Up-titration steps resulted in further significant decreases in both ABPM and HBPM. Both treatment regimens were well tolerated regarding adverse events or laboratory testing. In particular, peripheral edema known to be amlodipine dose dependent, appeared in only a few cases, none with the highest dose. Hypotension, orthostatic hypotension, and cough whatever the dose were infrequent. There were no treatment-related serious adverse events. CONCLUSION:Perindopril/indapamide/amlodipine in a single pill produces superior reductions in blood pressure compared with dual therapy. Triple therapy up-titration was well tolerated and effective leading to BP control rates of over 80%. Analysis of 24-h ABPM and HBPM results corroborated these findings.
Pleiotropic Effects of Losartan in Hypertensive Patients with Dyslipidemia.
Sivasubramaniam Sivakumar,Kumarasamy Banupriya
Journal of clinical and diagnostic research : JCDR
Introduction:In essential hypertension, the comorbidity of dyslipidemia is very common. In addition to hypertension, dyslipidemia is linked to cardiovascular disease, stroke and decline in renal function. Unlike other angiotensin receptor blockers, Losartan has been claimed to have unique pleiotropic property and thereby decreasing the risk of future cardiovascular complications. Aim:The present study was done to assess on the pleiotropic effect of losartan in newly diagnosed hypertensive patients with dyslipidemia. Materials and Methods:Fifty four hypertensive patients with dyslipidemia who fulfilled the eligible criteria and were willing to give informed consent were included in the study after getting Institutional Ethical Committee (IEC) approval. All the study participants were given tab. Losartan 50mg once daily for four weeks. At the end of 1st, 2nd, 3rd and 4th week, blood pressure control and compliance were monitored. At the end of 4th week all the baseline laboratory parameters like renal function test, liver function test, lipid prolife and random blood sugar were performed. The EQ-5D questionnaires were completed at two points during the study: at the patient's initial visit before enrollment in the study and after 4 weeks of Losartan therapy. Appropriate statistical methods were used to analyse the results.The primary endpoint was reduction in blood pressure and improvement in lipid profile and improvement in quality of life score from baseline after 4 weeks of losartan therapy. Results:Four patients were withdrawn due to non-compliance and totally 50 patients completed the study. The mean systolic blood pressure was reduced from 154.54 mm Hg to 138.16 mm Hg with p<0.0001 and the mean diastolic blood pressure was reduced from 91.56 mm Hg to 82.44 mm Hg with p<0.0001. There was a significant reduction in the mean total cholesterol from 189.52 to 180.46 mg/dl, mean LDL from 110.50 to 101.32 mg/dl and mean triglygeride from 135.68 to 127.70 mg/dl with p<0.0001. Improvements in anxiety and depression, as well as other dimensions in the QOL questionnaire, paralleled with improvement of the clinical picture. Conclusion:Based on the results of this study, Losartan is safe and effective in treating hypertensive patients with dyslipidemia in addition to its antihypertensive effect and it also has benefits of reducing serum glucose, lipid levels; and improvement in the quality of life.
Long-term effect of the perindopril/indapamide/amlodipine single-pill combination on left ventricular hypertrophy in outpatient hypertensive subjects.
Mazza Alberto,Townsend Danyelle M,Schiavon Laura,Torin Gioia,Lenti Salvatore,Rossetti Ciro,Rigatelli Gianluca,Rubello Domenico
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
BACKGROUND:Most antihypertensive drugs used in monotherapy or in combination therapy reduce the left ventricular mass index (LVMI). However, little is known about the effects on LVMI of a triple fixed-dose combination (TFC) therapy, containing in a single pill an angiotensin-converting enzyme inhibitor (ACEI), a diuretic and a calcium channel blocker (CCB). METHODS:In this prospective open-label study, 92 patients with essential hypertension were randomized to treatment with a TFC of perindopril/indapamide/amlodipine at different doses or a triple free combination therapy (FCT) including ACEI/diuretic/CCB. Office blood pressure (BP) measurement, 24 h-ambulatory BP monitoring and echocardiography were performed at baseline and during a 14-month follow-up. The BP variability (BPV) over 24 h was calculated as ± standard deviation of the daytime systolic BP. Differences between office and monitored BP and LVMI were evaluated by ANOVA for repeated measures. RESULTS:A significant BP-lowering effect was observed for both treatments. At follow-up, BPV was reduced in both the treatment groups vs. the baseline (14.0±1.5 vs. 17.0±1.8 and 16.2±2.1 vs. 17.6±2.3, respectively), but it was lower in the TFC vs. the FCT group (14.0±1.5 vs. 16.1±2.2, P < 0.05). LVMI was lower in both the treatment groups, but the change was greater for TFC vs. FCT (-8.3±4.9% vs. -2.0 ±2.1%, P < 0.0001). Left ventricular hypertrophy (LVH) regression was greater in the TFC vs. the FCT group (43.5% vs. 30.4%, P < 0.05). CONCLUSIONS:Independently of BP values achieved, the antihypertensive TFC therapy was more effective than FCT in LVMI reduction and LVH regression, possibly related to drugs' intrinsic properties and to BPV modulation.
Safety and Antihypertensive Effect of Selara® (Eplerenone): Results from a Postmarketing Surveillance in Japan.
Takahashi Shoko,Hiramatsu Megumi,Hotta Shinichi,Watanabe Yukie,Suga Osamu,Endo Yutaka,Miyamori Isamu
International journal of hypertension
Prospective postmarketing surveillance of Selara (eplerenone), a selective mineralocorticoid receptor antagonist, was performed to confirm its safety and efficacy for hypertension treatment in Japan. The change in blood pressure after initiation of eplerenone treatment was also examined. Patients with essential hypertension who were eplerenone-naïve were recruited regardless of the use of other antihypertensive drugs. For examination of changes in blood pressure, patients were excluded if eplerenone was contraindicated or used off-label. Patients received 50-100 mg of eplerenone once daily and were observed for 12 weeks. No treatments including antihypertensive drugs were restricted during the surveillance period. Across Japan, 3,166 patients were included for safety analysis. The incidence of adverse drug reactions was 2.4%. The major adverse drug reactions observed were hyperkalemia (0.6%), dizziness, renal impairment, and increased serum potassium (0.2% each). The mean systolic blood pressure decreased from 152.1 ± 19.0 mmHg to 134.8 ± 15.2 mmHg at week 12, and the mean diastolic blood pressure decreased from 85.8 ± 13.7 mmHg to 77.7 ± 11.4 mmHg. There were no significant new findings regarding the type or incidence of adverse reactions, and eplerenone had a clinically significant antihypertensive effect, leading to favorable blood pressure control.
Cost-benefit effectiveness of angiotensin-II receptor blockers in patients with uncomplicated hypertension: A comparative analysis.
Mazza Alberto,Sacco Antonella Paola,Townsend Danyelle M,Bregola Gianni,Contatto Edgardo,Cappello Isabella,Schiavon Laura,Ramazzina Emilio,Rubello Domenico
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
OBJECTIVE:The treatment of hypertensive patients (HTs) requires a long-term commitment of compliance for the patient and resources by the healthcare system. This poses an economic dilemma in countries where universal healthcare is standard. The aim of this study was to evaluate the costs/health benefit and effectiveness of treatment with angiotensin-II receptor blockers (ARBs) in uncomplicated essential hypertension. DESIGN AND METHODS:The daily and annual economic commitment for treating patients with ARBs was estimated using pharmacy dispensing records and the BP-lowering effects of candesartan, irbesartan, losartan, olmesartan, telmisartan and valsartan was evaluated retrospectively. In 114 HTs (mean age 59.4±13.5year, 57.5% men), the BP-lowering effect of ARBs as in monotherapy and in fixed-dose combination (FDC) with hydrochlorothiazide at the doses commonly used in the market to reach BP control (i.e. BP <140/90mmHg) was analyzed. The BP lowering-effect was evaluated after an average of 6-month follow-up consulting medical professionals. Analysis of variance for repeated measures was provided. RESULTS:Treatment with candesartan (14.1%) and olmesartan (32,4%) versus other ARBs resulted in a significant decrease in BP as for mono- than for FDC therapy. Our studies suggest that daily (data not shown) and annual costs of olmesartan were higher than candesartan as in mono- (4577.71±1120.55 vs. 894.25±127.75 €) than for FDC therapy (5715.90±459.90 vs. 1580.45±113.15 €). CONCLUSIONS:Treatment: of BP with candesartan appears to be the most favorable option in terms of cost-effectiveness coupled with favorable health outcomes. These data have some limitations, but open the question if candesartan should be preferred to olmesartan in BP management. Further prospective studies comparing ARBs based on their effect on BP control in uncomplicated HTs are needed for validation.
Effects of azilsartan compared with telmisartan on insulin resistance in patients with essential hypertension and type 2 diabetes mellitus: An open-label, randomized clinical trial.
Naruse Mitsuhide,Koike Yasuhiro,Kamei Nozomu,Sakamoto Ryuichi,Yambe Yuko,Arimitsu Michinori
BACKGROUND:Based on non-clinical data, it is expected that azilsartan, an angiotensin II receptor blocker, will help improve insulin resistance in addition to its hypotensive action. The present study is aimed to explore the effect of azilsartan compared to telmisartan on insulin sensitivity in hypertensive patients in the clinical setting. METHODS:This multicenter, randomized, open-label, parallel-group exploratory study was conducted in Japan. We randomized adult patients (≥20 years old) with grade I or II essential hypertension and coexisting type 2 diabetes (1:1) to receive either oral azilsartan (20 mg/day;17 patients) or telmisartan (40 mg/day;16 patients) for 12 weeks. The primary endpoint was the change in the homeostasis model assessment ratio of insulin resistance (HOMA-R) from the baseline at the end of the treatment period. We also evaluated its safety and efficacy on other diabetes-related variables and blood pressure. FINDINGS:The mean changes in HOMA-R at the end of treatment were 0.22 (95% CI, -1.09-1.52) in the azilsartan group and -0.23 (95% CI, -0.72-0.27) in the telmisartan group. We found no clinically remarkable changes between the groups in diabetes-related variables such as fasting blood glucose, fasting insulin, HbA1c (NGSP), HOMA-β, or 1,5-anhydroglucitol. Reductions in clinic systolic and diastolic blood pressure were observed at week 4 and the reduced levels were maintained throughout the treatment period in both groups. No serious treatment-emergent adverse events (TEAEs) were observed. Only one drug-related TEAE (mild decrease in blood pressure) was reported in one patient in the azilsartan group. CONCLUSION:Neither azilsartan nor telmisartan had any clinically remarkable effects on insulin resistance parameters when administered for 12 weeks to patients with grade I or II essential hypertension and coexisting type 2 diabetes mellitus. Azilsartan (20 mg/day) and telmisartan (40 mg/day) exerted comparable antihypertensive effects. TRIAL REGISTRATION:ClinicalTrials.gov NCT02079805.
Blood pressure lowering efficacy of beta-1 selective beta blockers for primary hypertension.
Wong Gavin W K,Boyda Heidi N,Wright James M
The Cochrane database of systematic reviews
BACKGROUND:Beta blockers are commonly used to treat hypertension. The blood pressure reading is the primary tool for physicians and patients to assess the efficacy of the treatment. The blood pressure lowering effect of beta-1 selective blockers is not known. OBJECTIVES:To quantify the dose-related effects of various doses and types of beta-1 selective adrenergic receptor blockers on systolic and diastolic blood pressure versus placebo in people with primary hypertension. SEARCH METHODS:We searched the Database of Abstracts of Reviews of Effectiveness (DARE) for related reviews.We searched the following databases for primary studies: the Cochrane Hypertension Specialised Register (All years to 15 October 2015), CENTRAL via the Cochrane Register of Studies Online (2015, Issue 10), Ovid MEDLINE (1946 to 15 October 2015), Ovid EMBASE (1974 to 15 October 2015) and ClinicalTrials.gov (all years to 15 October 2015).The Hypertension Group Specialised Register includes controlled trials from searches of CAB Abstracts, CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, Food Science and Technology Abstracts (FSTA), Global Health, LILACS, MEDLINE, ProQuest Dissertations & Theses, PsycINFO, Web of Science and the WHO International Clinical Trials Registry Platform (ICTRP).Electronic databases were searched using a strategy combining the Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE: sensitivity-maximizing version (2008 revision) with selected MeSH terms and free text terms. No language restrictions were used. The MEDLINE search strategy was translated into CENTRAL, EMBASE, the Hypertension Group Specialised Register and ClinicalTrials.gov using the appropriate controlled vocabulary as applicable. Full strategies are in Appendix 1. SELECTION CRITERIA:Randomised, double-blind, placebo-controlled parallel or cross-over trials. Studies had to contain a beta blocker monotherapy arm with fixed dose. People enrolled into the studies had to have primary hypertension at baseline. Duration of studies had to be between 3 weeks to 12 weeks. Drugs in this class of beta blockers are atenolol, betaxolol, bevantolol, bisoprolol, esmolol, metoprolol, nebivolol, pafenolol, practolol. DATA COLLECTION AND ANALYSIS:Two authors confirmed the inclusion of studies and extracted the data independently. Review Manager (RevMan) 5.3.5 was used to synthesise data. MAIN RESULTS:We identified 56 RCTs (randomised controlled trials) that examined the blood pressure (BP) lowering efficacy of beta-1 selective blockers (beta-1 blocker) in 7812 primary hypertensive patients. Among the included trials, 26 RCTs were parallel studies and 30 RCTs were cross-over studies, examining eight beta-1 blockers. Overall, the majority of beta-1 blockers studied significantly lowered systolic blood pressure (SBP) and diastolic blood pressure (DBP). In people with mild to moderate hypertension, beta-1 selective blockers lowered BP by an average of -10/-8 mmHg and reduced heart rate by 11 beats per minute. The maximum BP reduction of beta-1 blockers occurred at twice the starting dose. Individual beta-1 blockers did not exhibit a graded dose-response effect on SBP and DBP over the recommended dose range.Most beta-1 blockers tested significantly lowered heart rate. A graded dose-response of beta-1 blockers on heart rate was evident. Higher dose beta-1 blockers lowered heart rate more than lower doses. Individually and overall beta-1 blockers did not affect pulse pressure, which distinguishes them from other classes of drugs. AUTHORS' CONCLUSIONS:This review provides low quality evidence that in people with mild to moderate hypertension, beta-1 selective blockers lowered BP by an average of -10/-8 mmHg and reduced heart rate by 11 beats per minute as compared to placebo. The effect of beta-1 blockers at peak hours, -12/-9 mmHg, was greater than the reduction at trough hours, -8/-7 mmHg. Beta-1 selective blockers lowered BP by a greater magnitude than dual receptor beta-blockers and partial agonist beta-blockers, lowered BP similarly to nonselective beta-blockers. Beta-1 selective blockers lowered SBP by a similar degree and lowered DBP by a greater degree than diuretics, angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Because DBP is lowered by a similar extent to SBP, beta-1 selective blockers do not reduce pulse pressure.
Fimasartan versus perindopril with and without diuretics in the treatment of elderly patients with essential hypertension (Fimasartan in the Senior Subjects (FITNESS)): study protocol for a randomized controlled trial.
Kang Min-Gu,Kim Kwang-Il,Ihm Sang Hyun,Rhee Moo-Yong,Sohn Il Suk,Lee Hae-Young,Park Sungha,Jeon Eun-Seok,Song Jong-Min,Pyun Wook Bum,Sung Ki-Chul,Kim Moo Hyun,Kim Sang-Hyun,Kim Seok-Yeon,Kim Shin-Jae,Kim Eung Ju,Shin Jinho,Lee Sung Yun,Chun Kook-Jin,Jeong Jin-Ok,Chae Shung Chull,Yoo Ki Dong,Choi Young Jin,Park Yong Hwan,Kim Cheol-Ho
BACKGROUND:Hypertension is an important risk factor for cardiovascular disease, even in the elderly. Fimasartan is a new non-peptide angiotensin II receptor blocker with a selective type I receptor blocking effect. The objective of this study is to confirm the safety and the non-inferiority of the blood pressure-lowering effect of fimasartan compared with those of perindopril, which has been proven safe and effective in elderly patients with hypertension. METHODS:This is a randomized, double-blind, active-controlled, two-parallel group, optional-titration, multicenter, phase 3 study comparing the efficacy and safety of fimasartan and perindopril arginine. The study population consists of individuals 70 years old or older with essential hypertension. The primary outcome will be a change in sitting systolic blood pressure from baseline after the administration of the investigational product for 8 weeks. The secondary outcomes will be a change in sitting diastolic blood pressure from baseline and changes in sitting systolic blood pressure and diastolic blood pressure from baseline after the administration of the investigational product for 4, 16, and 24 weeks. The sample size will be 119 subjects for each group to confer enough power to test for the primary outcome. DISCUSSION:Research to confirm the efficacy and safety of a new medicine compared with those of previously proven anti-hypertensive drugs is beneficial to guide physicians in the selection of therapeutic agents. If it is confirmed that the new drug is not inferior to the existing drug, the drug will be considered as an option in the treatment of hypertension in elderly patients. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03246555 , registered on July 25, 2017.
A Randomized, Double-blind, Candesartan-controlled, Parallel Group Comparison Clinical Trial to Evaluate the Antihypertensive Efficacy and Safety of Fimasartan in Patients with Mild to Moderate Essential Hypertension.
Lee Jang Hoon,Yang Dong Heon,Hwang Jin Yong,Hur Seung Ho,Cha Tae Joon,Kim Ki-Sik,Kim Moo Hyun,Chun Kook Jin,Cha Gwang Soo,Hong Geu Ru,Lee Sang Gon,Kim Dong Soo,Kim Doo Il,Chae Shung Chull
PURPOSE:A new antihypertensive drug that selectively blocks angiotensin II receptor type 1, fimasartan, has a potent and rapidly acting antihypertensive effect. We investigated the antihypertensive effects of fimasartan 60 and 120 mg and its safety in comparison to 8 mg of candesartan. METHODS:This clinical trial is a multicenter, randomized, double-blind, active comparator, and parallel group study. Three hundred sixty-two individuals were screened, and 290 patients aged 19 to 75 years with mild to moderate hypertension (diastolic blood pressure [DBP], 90-110 mm Hg) were randomly assigned to 60 to 120 mg/d of fimasartan or 8 mg/d of candesartan after a 2-week placebo run-in period. Treatments were administered for 12 weeks without dosage adjustment. The primary end point was the differences in DBP changes at week 12. FINDINGS:After 12 weeks of treatment, DBP and systolic blood pressure (SBP) decreased significantly in all 3 groups. The decrease in DBP at week 12 was larger but not statistically significant in the fimasartan 60 mg compared with the candesartan 8 mg group with a mean (SD) difference of 1.72 (8.32) mm Hg (95% CI, -0.71 to 4.15 mm Hg; P = 0.17). The lower margin of the CI (-0.71 mm Hg) exceeded the noninferiority margin (-3.5 mm Hg). The DBP-lowering effect of fimasartan 120 mg was also nonsignificantly larger than candesartan 8 mg (difference, 1.58 [8.27] mm Hg; P = 0.20). The decrease in SBP was also nonsignificantly larger in the fimasartan 60 mg group compared with the candesartan 8 mg group (difference, 3.50 [12.63] mm Hg; P = .06). The SBP-lowering effect of fimasartan 120 mg was statistically larger than candesartan 8 mg (difference, 4.98 [13.99] mm Hg; P = .02). Response rate (DBP <90 mm Hg or DBP lowering >10 mm Hg at week 12) was also nonsignificantly greater in both fimasartan groups (Fimasartan 60 mg, 81%; fimasartan 120 mg, 72%; candesartan 8 mg, 71%). The safety profile of the fimasartan 60 mg and 120 mg was similar to candesartan 8 mg, with a slightly higher, but statistically not significant, incidence of hepatic enzyme elevation in fimasartan 120 mg. IMPLICATIONS:The antihypertensive effect of fimasartan, a newly available angiotensin II receptor type 1 blocker, is comparable, although not superior, to candesartan with a good safety profile. ClinicalTrials.gov identifier: NCT01135212.
Antihypertensive effect of azilsartan versus olmesartan in patients with essential hypertension: a meta-analysis.
Zhao Di,Liu Hui,Dong Pingshuan
Irish journal of medical science
OBJECTIVE:The comparison of antihypertensive effects between azilsartan and olmesartan in patients with essential hypertension has been investigated in several studies. The results were not consistent. We performed this meta-analysis determining the antihypertensive effect of azilsartan versus olmesartan in patients with essential hypertension. METHODS:Pubmed, Web of Science, and Cochrane Central were searched for all published randomized studies comparing the antihypertensive effects between azilsartan and olmesartan in patients with essential hypertension. RESULTS:The antihypertensive effects were assessed in 1402 patients included in five trials. The reduction of office systolic blood pressure treated with azilsartan was greater than olmesartan (weighted mean differences (WMD) - 2.15 (95% confidence interval (CI), - 3.78, - 0.53) mm Hg, p < 0.01). There was no significant difference in reduction of office diastolic blood pressure between azilsartan and olmesartan (WMD - 0.99 (95% CI, - 2.06, 0.08) mm Hg, p > 0.05). The reduction of office systolic blood pressure treated with azilsartan was greater than olmesartan at same dose for both drugs (WMD - 2.24 (95% CI, - 4.03, - 0.44) mm Hg, p < 0.05), whereas there was no significant difference in reduction of office diastolic blood pressure between azilsartan and olmesartan (WMD - 0.55 (95% CI, - 1.76, 0.66) mm Hg, p > 0.05). CONCLUSIONS:This meta-analysis provides the evidence that the reduction of office systolic blood pressure treated with azilsartan was greater than olmesartan in patients with essential hypertension. These findings suggest the importance of strict designed randomized controlled trials in determining antihypertensive effects of angiotensin II receptor blockers in clinical practice.
Using out-of-office blood pressure measurements in established cardiovascular risk scores: a secondary analysis of data from two blood pressure monitoring studies.
Lay-Flurrie Sarah,Stevens Richard,de Leeuw Peter,Kroon Abraham,Greenfield Sheila,Mohammed Mohammed,Gill Paramjit,Verberk Willem,McManus Richard
The British journal of general practice : the journal of the Royal College of General Practitioners
BACKGROUND:Blood pressure (BP) measurement is increasingly carried out through home or ambulatory monitoring, yet existing cardiovascular risk scores were developed for use with measurements obtained in clinics. AIM:To describe differences in cardiovascular risk estimates obtained using ambulatory or home BP measurements instead of clinic readings. DESIGN AND SETTING:Secondary analysis of data from adults aged 25-84 years in the UK and the Netherlands without prior history of cardiovascular disease (CVD) in two BP monitoring studies: the Blood Pressure in different Ethnic groups (BP-Eth) study and the Home versus Office blood pressure MEasurements: Reduction of Unnecessary treatment Study (HOMERUS). METHOD:The primary comparison was Framingham risk calculated using BP measured as in the Framingham study or daytime ambulatory BP measurements. Statistical significance was determined using non-parametric tests. RESULTS:In 442 BP-Eth patients (mean age = 58 years, 50% female [ = 222]) the median absolute difference in 10-year Framingham cardiovascular risk calculated using BP measured as in the Framingham study or daytime ambulatory BP measurements was 1.84% (interquartile range [IQR] 0.65-3.63, = 0.67). In 165 HOMERUS patients (mean age = 56 years, 46% female) the median absolute difference in 10-year risk for daytime ambulatory BP was 2.76% (IQR 1.19-6.39, <0.001) and only 8 out of 165 (4.8%) of patients were reclassified. CONCLUSION:Estimates of cardiovascular risk are similar when calculated using BP measurements obtained as in the risk score derivation study or through ambulatory monitoring. Further research is required to determine if differences in estimated risk would meaningfully influence risk score accuracy.
Familial factors in the antihypertensive response to lisinopril.
Hollenberg N K,Anzalone D A,Falkner B,Fisher N D,Hopkins P N,Hsueh W,Hutchinson H,Krauss R M,Price D A,Raskin P,Reaven G M
American journal of hypertension
BACKGROUND:Although it is widely recognized that there are familial elements in the pathogenesis of hypertension, remarkably little is known about the influence of family history on response to specific antihypertensive agents. METHODS:This study was designed to address that issue by comparing the depressor response to lisinopril in a dose range of 10 to 40 mg in 74 patients enrolled as sibling pairs. Because all patients were treated with lisinopril, ambulatory blood pressure monitoring (ABPM), an objective measure not influenced by the investigators, was used to assess the primary blood pressure (BP) outcome variable. RESULTS:Diastolic BP was highly correlated between sibling pairs at baseline (r = 0.476; P < .03) and on treatment (r = 0.524; P = .0021). Ethnicity/race had a striking influence on lisinopril dose and response rate. Among African American patients, 23 of 28 reached the top dose of 40 mg/day, whereas only 14 of 36 Caucasian patients reached that dose level. Among Caucasians, 92% responded, and only 48% of African Americans. Responders were characterized by being younger and heavier, having significantly lower microalbuminuria at baseline, higher baseline renal plasma flow (RPF), and higher urinary kallikrein. CONCLUSION:Among Caucasians, the presence of a hypertensive sibling predicts a striking therapeutic response to angiotensin converting enzyme inhibition.
Effects of amlodipine and valsartan on vascular damage and ambulatory blood pressure in untreated hypertensive patients.
Ichihara A,Kaneshiro Y,Takemitsu T,Sakoda M
Journal of human hypertension
The present study was performed to compare the long-term effects of 24-h ambulatory blood pressure (BP) control with amlodipine versus valsartan on vascular damage in untreated hypertensive patients. Amlodipine and valsartan have benefits on cardiovascular mortality and morbidity in hypertensive patients. Although ambulatory BP is associated with severity of target-organ damage in hypertensive patients, beneficial effects of ambulatory BP control with amlodipine versus valsartan on vascular damage have not been compared. Pulse wave velocity (PWV), intima-media thickness (IMT) of the carotid arteries, urinary albumin excretion (UAE) and 24-h ambulatory BP were determined in 100 untreated hypertensive patients before and 12 months after the start of antihypertensive therapy with amlodipine or valsartan. Amlodipine and valsartan decreased ambulatory BP similarly, but the variability of 24-h and daytime ambulatory systolic BP was significantly reduced by amlodipine but not by valsartan. The reduced variability of ambulatory systolic BP caused by amlodipine significantly contributed to the improvement of PWV, although both drugs decreased PWV similarly. Carotid IMT was unaffected by treatment with either drug. Valsartan significantly decreased UAE independently of its depressor effect, but amlodipine had no effect on UAE. These results suggest that the 24-h control of ambulatory BP with amlodipine had functionally improved the stiffened arteries of hypertensive patients by the end of 12 months of treatment, in part through reducing BP variability, whereas ambulatory BP control with valsartan decreased the arterial stiffness to the same degree as amlodipine without affecting BP variability maybe through some pleiotropic effects.
Zofenopril or irbesartan plus hydrochlorothiazide in elderly patients with isolated systolic hypertension untreated or uncontrolled by previous treatment: a double-blind, randomized study.
Modesti Pietro A,Omboni Stefano,Taddei Stefano,Ghione Sergio,Portaluppi Francesco,Pozzilli Paolo,Volpe Massimo,Arca Marcello,Calabrò Paolo,Fulgheri Paolo L Dessì,Bucci Marco,Berra Sergio,Villani Giovanni Q,Vladoianu Mircea,Popescu Elena,Velican Valerica G,Pirvu Octavian
Journal of hypertension
OBJECTIVE:To compare zofenopril + hydrochlorothiazide (Z + H) vs. irbesartan + hydrochlorothiazide (I + H) efficacy on daytime SBP in elderly (>65 years) patients with isolated systolic hypertension (ISH), untreated or uncontrolled by a previous monotherapy. METHODS:After a 1-week run-in, 230 ISH patients (office SBP ≥ 140 mmHg and DBP < 90 mmHg + daytime SBP ≥ 135 mmHg and daytime DBP < 85 mmHg) were randomized double-blind to 18-week treatment with Z + H (30 + 12.5 mg) or I + H (150 + 12.5 mg) once daily, in an international, multicenter study. Z and I doses could be doubled after 6 and 12 weeks, and nitrendipine 20 mg added at 12 weeks in nonnormalized patients. RESULTS:In the full analysis set (n = 216) baseline-adjusted average (95% confidence interval) daytime SBP reductions after 6 weeks (primary study end point) were similar (P = 0.888) with Z + H [7.7 (10.7, 4.6) mmHg, n = 107] and I + H [7.9 (10.7, 5.0) mmHg, n = 109]. Daytime SBP reductions were sustained during the study, and larger (P = 0.028) with low-dose Z + H at study end [16.2 (20.0, 12.5) mmHg vs. 11.2 (14.4, 7.9) mmHg I + H]. Daytime SBP normalization (<135 mmHg) rate was similar under Z + H and I + H at 6 and 12 weeks, but more common under Z + H at 18 weeks (68.2 vs. 56.0%, P = 0.031). Both drugs equally reduced SBP in the last 6 h of the dosing interval and homogeneously reduced SBP throughout the 24 h. The proportion of patients reporting drug-related adverse events was low (Z + H: 4.4% vs. I + H: 6.0%; P = 0.574). CONCLUSION:Elderly patients with ISH respond well to both low and high-dose Z or I combined with H.
Efficacy and safety of sacubitril/valsartan (LCZ696) add-on to amlodipine in Asian patients with systolic hypertension uncontrolled with amlodipine monotherapy.
Wang Ji-Guang,Yukisada Kimihiko,Sibulo Antonio,Hafeez Kudsia,Jia Yan,Zhang Jack
Journal of hypertension
OBJECTIVE:The objective of this study is to evaluate the efficacy and safety of sacubitril/valsartan (LCZ696, an angiotensin receptor and neprilysin inhibitor) add-on to amlodipine compared with amlodipine monotherapy in Asian patients with systolic hypertension uncontrolled with amlodipine. METHODS:Patients with mean clinic SBP at least 145 mmHg and less than 180 mmHg after a 4-week treatment with amlodipine 5 mg/day were randomized to receive LCZ696/amlodipine (200/5 mg/day) or amlodipine 5 mg/day for 8 weeks. The primary assessment was the superiority of LCZ696/amlodipine versus amlodipine in lowering 24-h ambulatory SBP from baseline to week 8. Secondary assessments included 24-h ambulatory DBP and pulse pressure (PP), daytime and night-time BP, clinic BP and PP, BP control/responder rate (<140/90 mmHg or a reduction ≥20/10 mmHg from baseline), and safety. RESULTS:Of the 371 patients screened, 266 (71.7%) patients (mean age 55.4 years; 24-h SBP/DBP 139.0/86.1 mmHg at baseline) who did not respond to 4-week treatment with amlodipine 5 mg/day were randomized. At week 8, LCZ696/amlodipine provided greater reductions in 24-h SBP compared with amlodipine monotherapy from baseline (-13.9 versus -0.8 mmHg, P < 0.001). All the secondary efficacy assessments were significantly (P < 0.001) in favour of LCZ696/amlodipine, for instance, 24-h PP (-5.8 versus -0.6 mmHg). Overall, the incidence of adverse events was 20.0% with LCZ696/amlodipine and 21.3% with amlodipine. CONCLUSION:LCZ696/amlodipine showed significantly greater 24-h ambulatory BP and PP reductions compared with amlodipine monotherapy. Both treatments were generally well tolerated. Therefore, LCZ696/amlodipine combination could be an effective treatment for patients with systolic hypertension uncontrolled with amlodipine.
Effects on 24-hour blood pressure variability of ace-inhibition and calcium channel blockade as monotherapy or in combination.
Parati Gianfranco,Castiglioni Paolo,Omboni Stefano,Faini Andrea
Cardiovascular events in hypertensives are associated with elevated average blood pressure (BP) and higher short-term BP variability (V), but little is known on treatment effects on BPV and on how to assess changes in short-term BPV. Aim of our study was to address the methodology of short-term BPV assessment and its reduction by Lercanidipine (L) or Enalapril (E) and their combination, through analysis of 24-hour ambulatory BP recordings from two studies including subjects of different age. Study-1: 64 middle-age hypertensives (52.9 ± 9.5 yrs) received L and E s.i.d. at 10 mg (L10, E10) or 20 mg doses (L20, E20) for 8 weeks. Study-2: 66 elderly hypertensives (65.5 ± 4.7 yrs) received placebo, L10, E20 and L10 + E20 s.i.d. for 4 weeks. In middle-age subjects, both L and E decreased mean BP and, at the highest dose, also short-term BPV. In elderly subjects, L10 alone or in combination with E20 reduced BPV. Treatment-induced reductions in BP levels and BPV were uncorrelated. Different methods for short-term BPV assessment did not always provide superimposable results in the elderly. Our study supports a better reduction of BPV by L in the elderly and by E + L combination at any age, suggesting BPV reduction to be independent from reduction in average BP.
Comparison of valsartan and amlodipine on ambulatory blood pressure variability in hypertensive patients.
Eguchi Kazuo,Imaizumi Yuki,Kaihara Toshiki,Hoshide Satoshi,Kario Kazuomi
Clinical and experimental hypertension (New York, N.Y. : 1993)
We tested the hypothesis that calcium channel blockers (CCBs: amlodipine group, n = 38)) are superior to angiotensin receptor blockers (ARBs: valsartan group, n = 38) against ambulatory blood pressure variability (BPV) in untreated Japanese hypertensive patients. Both drugs significantly reduced ambulatory systolic and diastolic BP values. With regard to BPV, standard deviation (SD) in SBP did not change with the administration of either drug, but the ARB significantly increased SD in awake DBP (12 ± 4-14 ± 4 mmHg). The ARB also significantly increased the coefficients of variation (CVs)in awake and 24-h SBP/DBP (all P < 0.05), but amlodipine did not change the CV. CCB significantly reduced the maximum values of awake SBP (193 ± 24-182 ± 27 mmHg, P = 0.02), sleep SBP (156 ± 18-139 ± 14 mmHg, P < 0 .001), and awake and sleep DBP (P < 0.01 in both cases), but the ARB did not change the maximum BP values. In conclusion, a once-daily morning dose of CCB amlodipine was more effective at controlling ambulatory BPV than ARB valsartan, especially in reducing maximum BP levels.
The Antihypertensive Efficacy of the Triple Fixed Combination of Perindopril, Indapamide, and Amlodipine: The Results of the PETRA Study.
Ábrahám György,Dézsi Csaba András
Advances in therapy
INTRODUCTION:The etiology of essential hypertension is multifactorial. Therefore, treatment with combinations of antihypertensive agents acting on multiple targets is necessary for successful therapy in the majority of patients. According to the experience and clinical data accumulated so far, combination therapy with three agents from different pharmacological classes is required in approx. 30% of patients in order to achieve long-term blood pressure control. The primary objective of the PETRA study was to evaluate the efficacy of blood pressure (BP) control with once daily administration of the different dosage strengths of the once-daily, triple fixed combination of perindopril, indapamide, and amlodipine. The evaluation was based on office BP readings and ambulatory blood pressure monitoring (ABPM) data gathered in routine clinical practice. METHODS:Data from 11,209 hypertensive patients (the proportion of female subjects was 47.6%) were processed and interpreted in a 3-month-long prospective, observational, non-interventional, open-label study conducted in 997 centers in Hungary. RESULTS:Mean baseline office BP was 156.58 ± 16.10/91.56 ± 9.33 mmHg (mean ± SD), whereas the mean duration of hypertension was 9.48 ± 7.19 years. Mean office BP decreased by 24.81 ± 15.47/11.41 ± 9.90 mmHg after switching to the triple fixed combination of perindopril, indapamide, and amlodipine (p < 0.0001). At the final visit 45.1% of patients took the 5/1.25/5 mg, 33.5% of them 10/2.5/5 mg, and 21.4% of them 10/2.5/10 mg strength of the perindopril/indapamide/amlodipine triple fixed combination. The 24-h blood pressure was obtained in 76 subjects. The mean 24-h BP decreased from 155.51 ± 17.43/85.28 ± 11.48 to 134.63 ± 12.51/77.83 ± 8.99 mmHg (p < 0.0001). Statistically significant (p < 0.0001) and clinically relevant improvement of a number of metabolic parameters-including total cholesterol (-8.6%), LDL-cholesterol (-11.4%), triglyceride (-12.1%), and fasting blood glucose (-6.6%) levels-was observed over the 3-month study period. CONCLUSIONS:During the 3 months of the PETRA study, the outstanding 24-h antihypertensive efficacy of the triple fixed combination of perindopril, indapamide, and amlodipine was confirmed both by office BP readings and by ABPM recordings. This combination may offer a new therapeutic option for hypertensive patients who have failed to achieve the desired BP target on their previous dual combination therapy. FUNDING:EGIS Pharmaceuticals PLC.
Effect of bedtime administration of blood-pressure lowering agents on ambulatory blood pressure monitoring results: A meta-analysis.
Sun Yuanyuan,Yu Xiao,Liu Junni,Zhou Nannan,Chen Liming,Zhao Yong,Li Xiaodong,Wang Jianchun,Cui Lianqun
BACKGROUND:Bedtime administration of antihypertensive drugs currently receives more at-tention, but no clear consensus has been reached on the blood pressure (BP)-lowering effect of this strategy. METHODS:We systematically searched literature for clinical trials of ingestion time of anti-hypertensive drugs evaluated by ambulatory blood pressure monitoring (ABPM) to perform a meta-analysis which aimed at determining the difference in diurnal, nocturnal, and 24-h mean of systolic BP (SBP) and diastolic BP (DBP), absolute BP reduction from baseline between bedtime administration group (experimental group) and morning (awaking) administration group (control group). RESULTS:The synthesis analysis showed that the level of BP in bedtime administration group was lower than the morning administration group, which reduced diurnal SBP/DBP by 1.67/1.13 mm Hg (p = 0.36/0.48), 24-h SBP/DBP by 2.78/0.36 mm Hg (p = 0.09/0.62), nocturnal SBP/DBP by 6.32/3.17 mm Hg (p = 0.03/0.007). Furthermore, there was lack of statistically significant differences in the diurnal mean of SBP/DBP reduction from baseline between the two groups (p = 0.94/0.85), but bedtime administration resulted in significant reduction from baseline in the nocturnal mean of SBP/DBP, by -4.72/-3.57 mm Hg (p = 0.01/0.05). Funnel plot demonstrated that there was no evidence of publication bias. CONCLUSIONS:Administration of ≥ 1 antihypertensive drugs at bedtime or evening results in a greater reduction of nocturnal hypertension than dosing in the morning without loss of efficacy of diurnal and 24 h mean BP reduction.
[Comparative Efficacy of the Influence of Fixed Combinations of Antihypertensive Drugs That Block the Renin-Angiotensin-Aldosterone System, With Thiazide Diuretics on the Parameters of Ambulatory Blood Pressure Monitoring].
Ostroumova O D,Garelik I A
AIM:to compare effects of fixed-dose combinations of antihypertensive drugs that block renin-angiotensin-aldosterone system (RAAS) with hydrochlorothiazide (HCT) on parameters of ambulatory blood pressure monitoring (ABPM). MATERIAL AND METHODS:Patients (n=50; 25 women, 25 men aged 40-75 years) with stage II essential hypertension who received no antihypertensive therapy for 12 weeks were randomized to receive once daily fixed-dose combinations of either valsartan/HCT (Val/HCT - group I) or quinapril/HCT (Quin/HCT - groupII) in starting doses of 80/12.5 or 10/12.5 mg, respectively. If target BP (<140 and 90 mm Hg) was not achieved after 2 weeks, doses were increased to 160/12.5 and 20/12.5 mg, respectively. Patients in whom target BP was not achieved after another 2 weeks were excluded from the study. Follow - up after achieving target BP was 12 weeks. RESULTS:Both combinations significantly (p<0.001) reduced office systolic and diastolic BP (SBP and DBP), however, BP decrease in group I was significantly (p<0.01) greater (-42.0+/-2,7 /-22.2+/-1.2 mm Hg) than in group II (-26,4+/-2,1/-6.6+/-0.4 mm Hg). Significant reduction of day- and night-time BP (p<0.001) observed in both groups was also more pronounced (p<0.01) in group I. In both groups we recorded significant (p<0.01) decreases of BP variability and morning BP rise. Variability of DBP at night (-3.3+/-0.2 mm Hg), magnitude and speed of morning DBP surge (-20.9+/-0.3 mm Hg and -3.4+/-0.2 mm Hg/hour, respectively) in group I decreased significantly (p<0.05) greater compared with same parameters in group II (-2.5+/-0.2 mm Hg, -17.7+/-0.3 mm Hg, -2.6+/-0.2 mm Hg/hour, respectively). CONCLUSION:Fixed-dose combinations of RAAS blockers and HCT provided reliable reduction of BP, BP variability, morning BP rise, and high percentage of achievement of target BP. Val/HCT combination was more effective in terms of reducing SBP, DBP and pulse BP levels at routine measurement, and day- and night-time SBP and DBP, night-time DBP variability, and rate of morning DBP rise.
Effects of lercanidipine hydrochloride versus felodipine sustained-release on day-to-day home blood pressure variability.
Xu Mengdan,Wu Ying,Wang Hao,Xu Xin,Zhao Shuiping,Zhang Mei,Jin Huigen-,Yan Jinchuan,Wang Bangning,Gong Jianbin,Lu Xiang,Peng Jianqiang,Dai Qiuyan
Current medical research and opinion
OBJECTIVE:The objective of this study was to compare the effectiveness of lercanidipine with felodipine in patients with mild-to-moderate hypertension on day-to-day home blood pressure variability. METHODS:This is a sub-study of a multicenter, randomized, open-label, parallel group and active controlled clinical trial. Hypertensive patients aged 18-75 (i.e. diastolic blood pressure ≥90 mmHg and <110 mmHg; systolic blood pressure ≥140 mmHg and <180 mmHg) and 24 h mean BP >130/80 mmHg) were eligible for this study. During the study, blood pressure (BP) and heart rate (HR) were recorded. The day-to-day BP variability (BPV) and HR variability (HRV) were obtained by the standard deviation (SD) of daily BP/HR average (of six readings) in 7 days. RESULTS:There were 186 patients (89 and 97 patients in the lercanidipine and felodipine groups, respectively) included in this study. Lercanidipine hydrochloride 10 mg/d and felodipine sustained-release tablets 5 mg/d were given to their respective groups. After 6 weeks of treatment, SD of home BP significantly reduced compared with baseline in both groups (P < .05) while SD of home HR also changed significantly after treatment (P < .05). There was no significant difference in SD of home BPV between the lercanidipine and felodipine groups after treatment. CONCLUSION:Treatment with lercanidipine and felodipine both resulted in reduction of BPV and HRV. There was no significant inter-group difference in reduction of BPV between the groups. Lercanidipine is an effective antihypertensive drug in improving BPV. National clinical trial: NCT01520285.
Twenty-four-hour ambulatory blood pressure changes in older patients with essential hypertension receiving monotherapy or dual combination antihypertensive drug therapy.
Lu Pei-Pei,Meng Xu,Zhang Ying,Li Yan-Qi,Wang Shu,Liu Li-Sheng,Wang Wen,Li Yu-Ling,Zhang Yu-Qing,Hu Ai-Hua,Zhou Xian-Liang,Ma Li-Hong
Journal of geriatric cardiology : JGC
Objective:To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs, as monotherapy or dual combination therapy, to improve daytime and nighttime BP control. Methods:We enrolled 1920 Chinese community-dwelling outpatients aged ≥ 60 years and compared ambulatory BP values and ambulatory BP control (24-hour BP < 130/80 mmHg; daytime mean BP < 135/85 mmHg; and nighttime mean BP < 120/70 mmHg), as well as nighttime BP dip patterns for monotherapy and dual combination therapy groups. Results:Patients' mean age was 71 years, and 59.5% of patients were women. Calcium channel blockers (CCBs) constituted the most common (60.3% of patients) monotherapy, and renin-angiotensin system (RAS) blockers combined with CCBs was the most common (56.5% of patients) dual combination therapy. Monotherapy with beta-blockers (BB) provided the best daytime BP control. The probabilities of having a nighttime dip pattern and nighttime BP control were higher in patients receiving diuretics compared with CCBs (OR = 0.52, = 0.05 and OR = 0.41, = 0.007, respectively). Patients receiving RAS/diuretic combination therapy had a higher probability of having controlled nighttime BP compared with those receiving RAS/CCB (OR = 0.45, = 0.004). Compared with RAS/diuretic therapy, BB/CCB therapy had a higher probability of achieving daytime BP control (OR = 1.27, = 0.45). Conclusions:Antihypertensive monotherapy and dual combination drug therapy provided different ambulatory BP control and nighttime BP dip patterns. BB-based regimens provided lower daytime BP, whereas diuretic-based therapies provided lower nighttime BP, compared with other antihypertensive regimens.
Office and ambulatory blood pressure control in hypertensive patients treated with different two-drug and three-drug combinations.
de la Sierra Alejandro,Banegas José R,Vinyoles Ernest,Gorostidi Manuel,Segura Julián,de la Cruz Juan J,Ruilope Luis M
Clinical and experimental hypertension (New York, N.Y. : 1993)
There is scarce information regarding ambulatory blood pressure (BP) achieved in daily practice with a wide range of antihypertensive drug combinations. We looked for differences in office and ambulatory BP among major drug combinations of two and three antihypertensive agents from a different drugs class. A total of 17187 patients treated with six types of two-drug combinations and 9724 treated with six types of three-drug combinations from the Spanish ABPM Registry were analyzed. We compared achieved office and ambulatory BP, as well as office (< 140/90 mmHg) and ambulatory (24-hour BP < 130/80; day BP < 135/85, and night BP < 120/70 mmHg) BP control among groups. The combination of renin-angiotensin system (RAS) blockers with diuretics and the triple combination of RAS blockers with diuretics and calcium channel blockers (CCB) were associated with lower values of 24-hour, daytime and nighttime BP, as well as more pronounced nocturnal BP dip. Compared with such combinations (reference), other double combinations had lower rates of ambulatory BP control. Moreover, triple combinations containing alpha blockers also had lower rates of ambulatory BP control. We conclude that even with similar office BP control, differences exist among antihypertensive two-drug and three-drug combinations with respect to ambulatory BP control achieved during treatment, with RAS blockers/diuretics and RAS blockers/CCBs/diuretics obtaining better control rates. This can help physicians choose among drug combinations in order to obtain further ambulatory BP reductions.
Randomized Crossover Trial of the Impact of Morning or Evening Dosing of Antihypertensive Agents on 24-Hour Ambulatory Blood Pressure.
Poulter Neil R,Savopoulos Christos,Anjum Aisha,Apostolopoulou Martha,Chapman Neil,Cross Mary,Falaschetti Emanuela,Fotiadis Spiros,James Rebecca M,Kanellos Ilias,Szigeti Matyas,Thom Simon,Sever Peter,Thompson David,Hatzitolios Apostolos I
Hypertension (Dallas, Tex. : 1979)
Some data suggest that nocturnal dosing of antihypertensive agents may reduce cardiovascular outcomes more than daytime dosing. This trial was designed to evaluate whether ambulatory blood pressure monitoring levels differ by timing of drug dosing. Patients aged 18 to 80 years with reasonably controlled hypertension (≤150/≤90 mm Hg) on stable therapy of ≥1 antihypertensive agent were recruited from 2 centers in London and Thessaloniki. Patients were randomized to receive usual therapy either in the morning (6 am-11 am) or evening (6 pm-11 pm) for 12 weeks when participants crossed over to the alternative timing for a further 12 weeks. Clinic blood pressures and a 24-hour recording were taken at baseline, 12, and 24 weeks and routine blood tests were taken at baseline. The study had 80% power to detect 3 mm Hg difference in mean 24-hour systolic blood pressure (α=0.05) by time of dosing. A 2-level hierarchical regression model adjusted for center, period, and sequence was used. Of 103 recruited patients (mean age, 62; 44% female), 95 patients (92%) completed all three 24-hour recordings. Mean 24-hour systolic and diastolic blood pressures did not differ between daytime and evening dosing. Similarly, morning and evening dosing had no differential impact on mean daytime (7 am-10 pm) and nighttime (10 pm-7 am) blood pressure levels nor on clinic levels. Stratification by age (≤65/≥65 years) or sex did not affect results. In summary, among hypertensive patients with reasonably well-controlled blood pressure, the timing of antihypertensive drug administration (morning or evening) did not affect mean 24-hour or clinic blood pressure levels. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT01669928.
Azilsartan in Patients With Mild to Moderate Hypertension Using Clinic and Ambulatory Blood Pressure Measurements.
Perez Alfonso,Cao Charlie
Journal of clinical hypertension (Greenwich, Conn.)
This was a phase 2, multicenter, randomized, parallel-group, double-blind dose-ranging study. Hypertensive adults (n=555) received one of five doses of azilsartan (AZL; 2.5, 5, 10, 20, 40 mg), olmesartan medoxomil (OLM) 20 mg, or placebo once daily. The primary endpoint was change in trough clinic diastolic blood pressure (DBP) at week 8. Compared with placebo, all AZL doses (except 2.5 mg) provided statistically and clinically significant reductions in DBP and systolic blood pressure (SBP) based on both clinic blood pressure (BP) and 24-hour ambulatory BP monitoring (ABPM). AZL 40 mg was statistically superior vs OLM. Clinic BP was associated with a pronounced placebo effect (-6 mm Hg), whereas this was negligible with ABPM (±0.5 mm Hg). Adverse event frequency was similar in the AZL and placebo groups. Based on these and other findings, subsequent trials investigated the commercial AZL medoxomil tablet at doses 20 to 80 mg/d using 24-hour ABPM.
Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses.
Brunström Mattias,Carlberg Bo
BMJ (Clinical research ed.)
OBJECTIVE:To assess the effect of antihypertensive treatment on mortality and cardiovascular morbidity in people with diabetes mellitus, at different blood pressure levels. DESIGN:Systematic review and meta-analyses of randomised controlled trials. DATA SOURCES:CENTRAL, Medline, Embase, and BIOSIS were searched using highly sensitive search strategies. When data required according to the protocol were missing but trials were potentially eligible, we contacted researchers, pharmaceutical companies, and authorities. ELIGIBILITY CRITERIA:Randomised controlled trials including 100 or more people with diabetes mellitus, treated for 12 months or more, comparing any antihypertensive agent against placebo, two agents against one, or different blood pressure targets. RESULTS:49 trials, including 73,738 participants, were included in the meta-analyses. Most of the participants had type 2 diabetes. If baseline systolic blood pressure was greater than 150 mm Hg, antihypertensive treatment reduced the risk of all cause mortality (relative risk 0.89, 95% confidence interval 0.80 to 0.99), cardiovascular mortality (0.75, 0.57 to 0.99), myocardial infarction (0.74, 0.63 to 0.87), stroke (0.77, 0.65 to 0.91), and end stage renal disease (0.82, 0.71 to 0.94). If baseline systolic blood pressure was 140-150 mm Hg, additional treatment reduced the risk of all cause mortality (0.87, 0.78 to 0.98), myocardial infarction (0.84, 0.76 to 0.93), and heart failure (0.80, 0.66 to 0.97). If baseline systolic blood pressure was less than 140 mm Hg, however, further treatment increased the risk of cardiovascular mortality (1.15, 1.00 to 1.32), with a tendency towards an increased risk of all cause mortality (1.05, 0.95 to 1.16). Metaregression analyses showed a worse treatment effect with lower baseline systolic blood pressures for cardiovascular mortality (1.15, 1.03 to 1.29 for each 10 mm Hg lower systolic blood pressure) and myocardial infarction (1.12, 1.03 to 1.22 for each 10 mm Hg lower systolic blood pressure). Patterns were similar for attained systolic blood pressure. CONCLUSIONS:Antihypertensive treatment reduces the risk of mortality and cardiovascular morbidity in people with diabetes mellitus and a systolic blood pressure more than 140 mm Hg. If systolic blood pressure is less than 140 mm Hg, however, further treatment is associated with an increased risk of cardiovascular death, with no observed benefit.
The effect of nebivolol and ramipril on selected biochemical parameters, arterial stiffness, and circadian profile of blood pressure in young men with primary hypertension: A 12-week prospective randomized, open-label study trial.
Walczak-Gałęzewska Marta,Szulińska Monika,Miller-Kasprzak Ewa,Pupek-Musialik Danuta,Bogdański Paweł
BACKGROUND:The pleiotropic effects of hypotensive drugs should always be taken into consideration. There is limited data on the effect of such drugs on reducing global cardiovascular risk in young hypertensives. The aim of this study was to evaluate the effect of nebivolol and ramipril on biochemical parameters, arterial stiffness, and circadian profile of blood pressure (BP) in young men undergoing treatment for hypertension (HT). METHODS:A total of 80 patients aged 16 to 28 years of age with grade 1 HT were enrolled into the prospective randomized, open-label trial. They were randomized to receive 5 mg of nebivolol or 5 mg of ramipril, daily. Arterial stiffness index (SI), the circadian profile of BP registered in ambulatory blood pressure monitoring (ABPM), and biochemical parameters-including lipid profile, insulinemia, glycemia, and high sensitivity C-reactive protein (hsCRP) levels-were evaluated before and after the twelve-week period. RESULTS:After the treatment period, we observed significant decreases in both ABPM systolic blood pressure (SBP) in group of nebivolol (P = .0007) and ramipril (P = .0001) and in ABPM diastolic blood pressure (DBP) in group of nebivolol (P = .0018) and ramipril (P = .0006). Reductions in the nondippers percentage were found in group of nebivolol and ramipril (P = .0077, P = .0001 respectively). Ramipril treatment resulted in a significant plausible modification in high-density lipoprotein (HDL) (P = .0390), glucose (P = .0213), and hsCRP (P = .0053) concentrations, as well as decreased SI (P = .0009) value, while nebivolol treatment showed no such benefits. CONCLUSIONS:Despite the similar hypotensive effect of nebivolol and ramipril, ramipril seems to possess better clinical potential in reducing cardiovascular risk in young men with HT.
First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension.
Chen Yu Jie,Li Liang Jin,Tang Wen Lu,Song Jia Yang,Qiu Ru,Li Qian,Xue Hao,Wright James M
The Cochrane database of systematic reviews
BACKGROUND:This is the first update of a Cochrane Review first published in 2015. Renin angiotensin system (RAS) inhibitors include angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and renin inhibitors. They are widely prescribed for treatment of hypertension, especially for people with diabetes because of postulated advantages for reducing diabetic nephropathy and cardiovascular morbidity and mortality. Despite widespread use for hypertension, the efficacy and safety of RAS inhibitors compared to other antihypertensive drug classes remains unclear. OBJECTIVES:To evaluate the benefits and harms of first-line RAS inhibitors compared to other first-line antihypertensive drugs in people with hypertension. SEARCH METHODS:The Cochrane Hypertension Group Information Specialist searched the following databases for randomized controlled trials up to November 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA:We included randomized, active-controlled, double-blinded studies (RCTs) with at least six months follow-up in people with elevated blood pressure (≥ 130/85 mmHg), which compared first-line RAS inhibitors with other first-line antihypertensive drug classes and reported morbidity and mortality or blood pressure outcomes. We excluded people with proven secondary hypertension. DATA COLLECTION AND ANALYSIS:Two authors independently selected the included trials, evaluated the risks of bias and entered the data for analysis. MAIN RESULTS:This update includes three new RCTs, totaling 45 in all, involving 66,625 participants, with a mean age of 66 years. Much of the evidence for our key outcomes is dominated by a small number of large RCTs at low risk for most sources of bias. Imbalances in the added second-line antihypertensive drugs in some of the studies were important enough for us to downgrade the quality of the evidence.Primary outcomes were all-cause death, fatal and non-fatal stroke, fatal and non-fatal myocardial infarction (MI), fatal and non-fatal congestive heart failure (CHF) requiring hospitalizations, total cardiovascular (CV) events (fatal and non-fatal stroke, fatal and non-fatal MI and fatal and non-fatal CHF requiring hospitalization), and end-stage renal failure (ESRF). Secondary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR).Compared with first-line calcium channel blockers (CCBs), we found moderate-certainty evidence that first-line RAS inhibitors decreased heart failure (HF) (35,143 participants in 5 RCTs, risk ratio (RR) 0.83, 95% confidence interval (CI) 0.77 to 0.90, absolute risk reduction (ARR) 1.2%), and that they increased stroke (34,673 participants in 4 RCTs, RR 1.19, 95% CI 1.08 to 1.32, absolute risk increase (ARI) 0.7%). Moderate-certainty evidence showed that first-line RAS inhibitors and first-line CCBs did not differ for all-cause death (35,226 participants in 5 RCTs, RR 1.03, 95% CI 0.98 to 1.09); total CV events (35,223 participants in 6 RCTs, RR 0.98, 95% CI 0.93 to 1.02); and total MI (35,043 participants in 5 RCTs, RR 1.01, 95% CI 0.93 to 1.09). Low-certainty evidence suggests they did not differ for ESRF (19,551 participants in 4 RCTs, RR 0.88, 95% CI 0.74 to 1.05).Compared with first-line thiazides, we found moderate-certainty evidence that first-line RAS inhibitors increased HF (24,309 participants in 1 RCT, RR 1.19, 95% CI 1.07 to 1.31, ARI 1.0%), and increased stroke (24,309 participants in 1 RCT, RR 1.14, 95% CI 1.02 to 1.28, ARI 0.6%). Moderate-certainty evidence showed that first-line RAS inhibitors and first-line thiazides did not differ for all-cause death (24,309 participants in 1 RCT, RR 1.00, 95% CI 0.94 to 1.07); total CV events (24,379 participants in 2 RCTs, RR 1.05, 95% CI 1.00 to 1.11); and total MI (24,379 participants in 2 RCTs, RR 0.93, 95% CI 0.86 to 1.01). Low-certainty evidence suggests they did not differ for ESRF (24,309 participants in 1 RCT, RR 1.10, 95% CI 0.88 to 1.37).Compared with first-line beta-blockers, low-certainty evidence suggests that first-line RAS inhibitors decreased total CV events (9239 participants in 2 RCTs, RR 0.88, 95% CI 0.80 to 0.98, ARR 1.7%), and decreased stroke (9193 participants in 1 RCT, RR 0.75, 95% CI 0.63 to 0.88, ARR 1.7% ). Low-certainty evidence suggests that first-line RAS inhibitors and first-line beta-blockers did not differ for all-cause death (9193 participants in 1 RCT, RR 0.89, 95% CI 0.78 to 1.01); HF (9193 participants in 1 RCT, RR 0.95, 95% CI 0.76 to 1.18); and total MI (9239 participants in 2 RCTs, RR 1.05, 95% CI 0.86 to 1.27).Blood pressure comparisons between first-line RAS inhibitors and other first-line classes showed either no differences or small differences that did not necessarily correlate with the differences in the morbidity outcomes.There is no information about non-fatal serious adverse events, as none of the trials reported this outcome. AUTHORS' CONCLUSIONS:All-cause death is similar for first-line RAS inhibitors and first-line CCBs, thiazides and beta-blockers. There are, however, differences for some morbidity outcomes. First-line thiazides caused less HF and stroke than first-line RAS inhibitors. First-line CCBs increased HF but decreased stroke compared to first-line RAS inhibitors. The magnitude of the increase in HF exceeded the decrease in stroke. Low-quality evidence suggests that first-line RAS inhibitors reduced stroke and total CV events compared to first-line beta-blockers. The small differences in effect on blood pressure between the different classes of drugs did not correlate with the differences in the morbidity outcomes.
A Meta-analysis of antihypertensive effect of telmisartan versus candesartan in patients with essential hypertension.
Zhao Di,Liu Hui,Dong Pingshuan
Clinical and experimental hypertension (New York, N.Y. : 1993)
OBJECTIVE:The comparison of antihypertensive effects between telmisartan and candesartan in patients with essential hypertension has been investigated in several small studies. The results were not consistent. We performed this meta-analysis determining the antihypertensive effect of telmisartan versus candesartan in these patients. METHODS:We searched Pubmed, Web of Science, and Cochrane Central for all published studies comparing the antihypertensive effects between telmisartan and candesartan in patients with essential hypertension. RESULTS:The antihypertensive effects were assessed in 302 patients included in 4 trials with a mean follow-up of 10 ± 4 weeks. There were no significant differences between telmisartan and candesartan in reduction of systolic blood pressure (SBP) and diastolic BP (DBP) in patients with essential hypertension (weighted mean differences (WMD) for SBP 1.98 mm Hg (95% confidence interval (CI), -0.53, 4.49), p > 0.05; WMD for DBP 0.26 mm Hg (95% CI, -1.65, 2.16), p > 0.05), respectively. In a sub-analysis including 2 randomized studies, there was not a significant difference for the reduction of SBP (WMD 0.90 (95% CI, -2.88, 4.68) mm Hg, p > 0.05) or DBP (WMD -0.80 (95% CI, -3.40, 1.81) mm Hg, p > 0.05) treated with telmisartan or candesartan. CONCLUSIONS:This meta-analysis provides the evidence that the antihypertensive effects of telmisartan and candesartan are similar on SBP and DBP reduction in patients with essential hypertension, suggesting that strict designed randomized controlled trial would be helpful to compare antihypertensive effects of angiotensin II receptor blockers (ARBs) and improve the choice of ARBs in antihypertensive therapy.