Comparison of amlodipine versus other calcium channel blockers on blood pressure variability in hypertensive patients in China: a retrospective propensity score-matched analysis.
Zhang Lin,Yang JinKui,Li LanTing,Liu DongDong,Xie XiaoPing,Dong Peng,Lin Yong
Journal of comparative effectiveness research
AIM:Reducing the fluctuation of blood pressure has recently been recognized as a potential target for improving management of hypertension to prevent cardiovascular events, particularly for strokes. Some randomized controlled trials demonstrated that amlodipine can effectively reduce blood pressure as a well-established, long-acting calcium channel blocker (CCB). However, few data are available for amlodipine on blood pressure variability (BPV) in China in a real-world setting. This study aimed to assess the effect of amlodipine versus other CCB antihypertensive agents on BPV. MATERIALS & METHODS:A retrospective propensity score-matched analysis was conducted, which retrieved the encounter data from 5582 hypertensive inpatients (with a median age of 69, female percentage of 48%, diastolic blood pressure ≥40 and <150 mmHg; systolic blood pressure (SBP) ≥70 mmHg and <260 mmHg), who had taken at least one antihypertensive agent and completed at least three SBP measurements during the visit. International Classification of Diseases was used to identify the hypertensive patients. BPV was calculated with standard deviation (SD) and coefficient of variation (CV) of SBP during a single inpatient visit. The Propensity Score Matching was used to balance the cohort of patients prescribed amlodipine or other CCBs. A series of appropriate statistical tests were applied to the propensity score-matched samples to examine the different effects on BPV. Additionally, the hypertensive patients with comorbidity such as coronary artery disease, diabetes mellitus, myocardial infarction, heart failure and chronic kidney disease were analyzed. RESULTS:For the hypertensive patients (n = 1756, for each cohort), patients prescribed amlodipine showed lower BPV than patients prescribed other CCBs (12.90 vs 13.76 mmHg, p < 0.05 [SD] and 9.47 vs 10.06, p < 0.05 [CV]). For the hypertensive patients with comorbidity (n = 1080, for each cohort), patients prescribed amlodipine had lower BPV than patients prescribed other CCBs as well (13.24 vs 14.23 mmHg, p < 0.05 [SD] and 9.66 vs 10.28, p < 0.05 [CV]). CONCLUSION:amlodipine was associated with lower BPV than other CCBs for both hypertensive patients and hypertensive patients with comorbidity.
[Blood Pressure Variability. Visit-to-Visit Blood Pressure Variability].
Ostroumova O D,Borisova E V,Pavleeva E E
The article is devoted to the modern state of the problem of blood pressure variability (BPV). Along with discussion of classification and methods of diagnosis it contains data on prognostic value of visit-to-visit BPV. We have also reviewed effect on BPV of various regimens of antihypertensive therapy and presented evidence base supporting ability of amlodipine/perindopril fixed dose combination to lower visit-to-visit BPV.
Predictors of visit-to-visit blood pressure variability in patients with hypertension: an analysis of trials with an amlodipine treatment arm.
Wang Ji-Guang,Zhou Duo,Jeffers Barrett W
Journal of the American Society of Hypertension : JASH
We conducted a post hoc analysis of blood pressure (BP) data from long-term antihypertensive trials to identify predictors of visit-to-visit BP variability (BPV). BPV was defined as the within-subject coefficient of variation in systolic BP from week 12 onward. BP data from the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, Comparison of Amlodipine Versus Enalapril to Limit Occurrences of Thrombosis, NY92011, and R-0510 trials were pooled and dichotomized into top 25th and bottom 75th percentiles because of positive skew. Significant (P < .001) predictors of BPV within the top 25th percentile were identified using logistic regression. The baseline characteristics of the pooled cohort (n = 47,558) were similar between patients who received amlodipine (n = 17,499) versus other antihypertensive drugs (n = 29,491). BPV in the top 25th percentile was lower with amlodipine versus other treatments (13.7 ± 3.2 vs. 14.3 ± 3.5), with single-study analyses of Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, and Comparison of Amlodipine Versus Enalapril to Limit Occurrences of Thrombosis all showing BPV was the lowest with amlodipine. Baseline diastolic BP, estimated glomerular filtration rate, and smoking were predictors of BPV, with significant two-way interactions between smoking and both age and body mass index and between systolic BP or diastolic BP and being randomized to treatment other than amlodipine. In conclusion, analysis of BPV required transformation of BP data. After transformation, a number of baseline variables and combinations of variables were predictors of BPV.
The efficacy and safety of fixed-dose combination of amlodipine/benazepril in Chinese essential hypertensive patients not adequately controlled with benazepril monotherapy: a multicenter, randomized, double-blind, double-dummy, parallel-group clinical trial.
Yan Pingping,Fan Weihu,
Clinical and experimental hypertension (New York, N.Y. : 1993)
This double-blind, double-dummy clinical trial evaluated the efficacy and safety of two strengths of fixed-dose combination of amlodipine/benazepril in Chinese hypertensive patients not adequately controlled with benazepril. Of 442 patients who received treatment with benazepril 10 mg for 4 weeks, 341 patients failed to achieve to diastolic blood pressure (DBP) <90 mmHg. These non-responders were randomized to receive amlodipine/benazepril 2.5/10 mg, or amlodipine/benazepril 5/10 mg, or benazepril 10 mg for 8 weeks. BP reductions with amodipinel/benazepril 2.5/10 mg (15.2/11.8 mmHg) or amlodipine/benazepril 5/10 mg (15.4/12.4 mmHg) were significantly greater than that with benazepril 10 mg (9.88/9.46 mmHg) at study end (p < 0.01, combination versus benazepril). BP control rate was 83.8% with amlodipine/benazepril 2.5/10 mg, 80.2% with amlodipine/benazepril 5/10 mg, 64.9% with benazepril 10 mg at study end (p < 0.01, combination versus benazepril). Three groups were generally well tolerated. Our study indicated that amlodipine/benazepril fixed-dose combination offered significant additional BP reductions and BP control rate compared with the continuation of benazepril monotherapy. No significant differences were observed in both BP reductions and BP control rate between amlodipine/benazepril 2.5/10 mg and amlodipine/benazepril 5/10 mg.
Influence of West African Ethnicity and Gender on Beta-Cell Function and Insulin Sensitivity in Essential Hypertensives Treated with Hydrochlorothiazide and Hydrochlorothiazide-lisinopril Combination.
Olamoyegun Micheal,Kolawole Babatope,Ajayi Adesuyi A L
Journal of pharmacology & pharmacotherapeutics
OBJECTIVE:To assess the effects of hydrochlorothiazide (HCT) given alone and in combination with an angiotensin-converting enzyme inhibitor (ACEI) on beta-cell function in a negroid population to further explore possible ethnic differences in the effect of antihypertensive drugs on homeostasis model assessment - insulin resistance (HOMA-IR). MATERIALS AND METHODS:A total of 80 newly diagnosed Nigerian essential hypertensive patients were assigned to receive either HCT 25 mg daily or both HCT and lisinopril (Lis; 25/10 mg daily) in an open-label study for 12 weeks. The treatment groups were well matched in clinical and demographic baseline features. Changes in HOMA-IR from baseline to end of study (week 12), fasting plasma glucose (FPG), serum potassium, serum insulin, and blood pressure over the same period were also evaluated. RESULTS:After 12 weeks, mean delta HOMA-IR (and %) was higher in the HCT monotherapy group; although, this change did not reach statistical significance in both groups -0.1 ± 7.1, = 0.538 (HCT) and 0.6 ± 4.2 = 0.913 (HCT + Lis); an insignificant increase was observed in FPG and serum insulin in both groups, whereas serum potassium decreased in similar fashion. Blood pressure reduction was similar in both groups. Analysis of HOMA-IR change according to gender in response to HCT mono- or combination therapy with Lis showed no significant difference. CONCLUSIONS:HCT monotherapy in hypertensive indigenous Nigerians, was not associated with worse metabolic effects when compared with combination therapy using Lis, an ACEI after 12 weeks. Low-dose thiazide diuretic as first-line antihypertensive medication may be safe in the short-term, further larger and long-term studies are needed to corroborate this finding.
A randomized, double-blind study to evaluate the efficacy and safety of a single-pill combination of telmisartan 80 mg/amlodipine 5 mg versus amlodipine 5 mg in hypertensive Asian patients.
Zhu Dingliang,Gao Pingjin,Holtbruegge Werner,Huang Chenglei
The Journal of international medical research
OBJECTIVE:To investigate the efficacy and safety of telmisartan 80 mg/amlodipine 5 mg (T80/A5) single-pill combination versus A5 in patients with essential hypertension not adequately controlled on A5 monotherapy. METHODS:Asian patients ≥18 years old, with inadequately controlled blood pressure (BP) at enrolment, who failed to achieve a seated diastolic BP (DBP) goal (≥90 mmHg) following 6-weeks' open-label A5 treatment, were randomly allocated 1 : 1 to 8 weeks' double-blind treatment with T80/A5 single-pill combination or A5. RESULTS:A total of 324 patients entered the double-blind treatment phase. The adjusted mean ± SE reduction in seated trough DBP from baseline to week 8 was significantly greater with T80/A5 (12.4 ± 1.0 mmHg) than A5 (10.2 ± 0.9 mmHg [primary endpoint, n = 314]). Results were similar in the subset of 262 Chinese patients. Treatment-related adverse events were 1.9% with T80/A5 and 2.4% with A5. CONCLUSIONS:In Asian patients with hypertension, T80/A5 single-pill combination provided improved BP reduction after 8 weeks' treatment compared with A5 monotherapy. Both treatments were well tolerated.
Clinical use of azelnidipine in the treatment of hypertension in Chinese patients.
Chen Bi-Lian,Zhang Yin-Zhuang,Luo Jian-Quan,Zhang Wei
Therapeutics and clinical risk management
BACKGROUND:Hypertension is the most common chronic disease and the calcium channel antagonist is the most popularly used antihypertensive drug in Chinese patients. Azelnidipine is a third generation and long-acting dihydropyridine calcium channel antagonist. A series of research has demonstrated that azelnidipine produced an effective antihypertensive effect in patients with essential hypertension. Now it is need to summarize clinical use of azelnidipine in the treatment of hypertension in Chinese patients. METHODS:Relevant literature was identified by performing searches in PubMed and CNKI (China National Knowledge Infrastructure), covering the period from January 2003 (the year azelnidipine was launched) to July 2014. We included studies that described pharmacology of azelnidipine, especially the pharmacokinetics, clinical efficacy, and safety and tolerability of azelnidipine in a Chinese population. The full text of each article was strictly reviewed, and data interpretation was performed. RESULTS:In Chinese healthy volunteers, a single-dose oral administration of azelnidipine 8-16 mg had a peak plasma concentration of 1.66-23.06 ng/mL and time to peak plasma concentration was 2.6-4.0 hours and the area under the plasma concentration versus time curve from time 0 hour to 96 hours was 17.9-429 ng/mL·h and elimination half-life was 16.0-28.0 hours. A number of clinical trials have demonstrated that azelnidipine produced a significant reduction in blood pressure in Chinese patients with mild-to-moderate hypertension, which was similar to that of other effective antihypertensive drugs such as amlodipine, zofenopril, and nifedipine. In addition to its antihypertensive effect, azelnidipine had other cardiovascular protective effects as well, like anti-oxidative action, decreasing heart rate, and improving systolic and diastolic function. Azelnidipine was generally well tolerated in Chinese patients and no severe adverse events were observed. CONCLUSION:Azelnidipine is effective and safe in the treatment of hypertension in Chinese patients.
Randomized trial comparing the effects of a low-dose combination of nifedipine GITS and valsartan versus high-dose monotherapy on central hemodynamics in patients with inadequately controlled hypertension: FOCUS study.
Park Jeong Bae,Ha Jong-Won,Jung Hae-Ok,Rhee Moo-Yong,
Blood pressure monitoring
OBJECTIVES:Measurement of central blood pressure provides prognostic information beyond conventional peripheral blood pressure (BP). However, few studies have directly compared the effects of antihypertensives on central hemodynamics. This study investigated the effects of a low-dose combination of nifedipine Gastrointestinal Therapeutic System (GITS) and valsartan versus high-dose monotherapy with either agent in reducing central BP in essential hypertension inadequately controlled by low-dose monotherapy. MATERIALS AND METHODS:In this prospective, open-label, randomized, active-controlled, multicenter 8-week study, patients not meeting the target BP after 4 weeks of treatment with low-dose monotherapy were randomized to receive nifedipine GITS 30 mg plus valsartan 80 mg (N30+V80), nifedipine GITS 60 mg (N60), or valsartan 160 mg (V160) for a further 4 weeks. Central hemodynamics were measured by applanation tonometry. RESULTS:A total of 391 patients were enrolled. Reduction in central systolic BP from baseline to week 8, the primary efficacy variable, was significantly greater in the N30+V80 group (-27.2±14.7 mmHg) and the N60 group (-27.1±16.5 mmHg) compared with V160 group (-14.4±16.6 mmHg). Decrease in the augmentation index in the N60 group was significantly greater compared with V160 alone, without differences between combination therapy and either high-dose monotherapy. Decreases in brachial systolic BP were significantly greater in the N30+V80 and N60 groups than in the V160 group. By multiple regression analysis, most differences in drug effects on central hemodynamics disappeared after controlling for changes in peripheral BP. A low rate of adverse events occurred in all treatment groups. CONCLUSION:A low-dose combination of nifedipine GITS plus valsartan or high-dose nifedipine was more effective in improving central hemodynamics than high-dose valsartan in patients with hypertension, mostly because of the improvement in peripheral (brachial) hemodynamics.
Efficacy and safety of azilsartan medoxomil/chlortalidone fixed-dose combination in hypertensive patients uncontrolled on azilsartan medoxomil alone: A randomized trial.
Collier David J,Juhasz Attila,Agabiti-Rosei Enrico,Lloyd Eric,Hisada Michie,Zhao Lin,Kupfer Stuart,Caulfield Mark J
Journal of clinical hypertension (Greenwich, Conn.)
Patients with grade 2-3 essential hypertension and postplacebo mean clinic systolic blood pressure (SBP) 160-190 mm Hg and 24-hour SBP 140-175 mm Hg by ambulatory blood pressure monitoring (ABPM) received 40 mg azilsartan medoxomil (AZL-M) monotherapy for 4 weeks. "Nonresponders" were then randomized to 8 weeks of double-blind treatment with AZL-M 40 mg, AZL-M/chlortalidone (CLD) 40/25, or AZL-M/CLD 40/12.5 mg. After 8 weeks, mean clinic SBP change was -21.1 (±1.04) mm Hg for AZL-M/CLD 40/25 mg, -15.8 (±1.08) mm Hg for AZL-M/CLD 40/12.5 mg, and -6.4 (±1.05) mm Hg for AZL-M 40 mg (P < 0.001 for both AZL-M/CLD vs AZL-M, ANCOVA). Drug discontinuation rates were 8.9% (AZL-M/CLD 40/25 mg), 7.5% (AZL-M 40 mg), and 3.9% (AZL-M/CLD 40/12.5 mg). Creatinine increased in 8.1% (AZL-M/CLD 40/25), 3.1% (AZL-M/CLD 40/12.5 mg), and 3.0% (AZL-M 40 mg) of patients. AZL-M/CLD was effective and well tolerated in patients not achieving blood pressure targets with AZL-M.
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.
Telmisartan in combination with hydrochlorothiazide 12.5 mg for the management of patients with hypertension.
Neldam Steen,Schumacher Helmut,Kjeldsen Sverre E,Neutel Joel M
Current medical research and opinion
OBJECTIVE:To compare the efficacy and safety of telmisartan 40 mg (T40) or 80 mg (T80) plus hydrochlorothiazide 12.5 mg (H12.5) single-pill combinations (SPCs) with telmisartan monotherapies, in a pooled analysis of patients with mild to moderate hypertension. METHODS:Six phase 3, double-blind studies of 8 weeks' duration that assessed the T/H12.5 SPC and T40 or T80 monotherapy, were included in the analysis. Data was pooled separately for the two T40 non-responder studies (T40 NR group, two T80 non-responder studies (T80 NR group), and the two factorial design dose-response studies (FD-DR group). RESULTS:After 8 weeks' treatment, the adjusted mean reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP), and the SBP, DBP, and blood pressure (BP) goal rates were significantly higher with the T40/H12.5 SPC than T40 in the T40 NR group and with the T80/H12.5 SPC than T80 in the T80 NR group. In the FD-DR group, the adjusted mean reduction in SBP and DBP, and DBP goal rates were significantly higher for T40/H12.5 versus T40. The percentage of patients with an adverse event was numerically higher with T40/H12.5 versus T40 in the T40 NR group, and was similar in telmisartan monotherapies and the T/H12.5 SPCs in the T80 NR group and FD-DR group. A limitation of this study is the retrospective and pooled nature of the analysis. Also, >75% of patients were <65 years of age, which limits the applicability of the results to older patients. CONCLUSIONS:In patients with mild to moderate hypertension, 8 weeks' treatment with the T/H12.5 SPC is significantly more efficacious than telmisartan monotherapies. The safety and tolerability of the T/H12.5 SPC are comparable to that of telmisartan monotherapy and consistent with that reported in previous studies.
Randomized trial comparing the velocities of the antihypertensive effects on home blood pressure of candesartan and candesartan with hydrochlorothiazide.
Hosaka Miki,Metoki Hirohito,Satoh Michihiro,Ohkubo Takayoshi,Asayama Kei,Kikuya Masahiro,Inoue Ryusuke,Obara Taku,Hirose Takuo,Imai Yutaka,
Hypertension research : official journal of the Japanese Society of Hypertension
We aimed to evaluate the hypotensive effect and the time to attain the maximal antihypertensive effect (stabilization time) of 8 mg candesartan/6.25 mg hydrochlorothiazide (HCTZ) combination therapy (combination regimen) and therapy with an increased candesartan dose (12 mg; maximum dose regimen) using home blood pressure (BP) measurements. A prospective, multicenter, open-label, randomized, comparative trial was conducted. Essential hypertensive patients who failed to achieve adequate BP control (systolic BP (SBP) ⩽ 135 mm Hg) on 8 mg candesartan alone were randomized to two groups: the combination regimen (n=103) and the maximum dose regimen (n=103). Home morning SBP reduction at 8 weeks after randomization was 11.4 ± 1.3 mm Hg in the combination regimen and 7.8 ± 1 .2 mm Hg in the maximum dose regimen. The combination regimen provided additional reduction of 4.0 mm Hg (95% confidence interval (CI): 0.8-7.2 mm Hg, P=0.01) in home morning SBP over the maximum dose regimen at 8 weeks after randomization. The maximal antihypertensive effect and stabilization time for home SBP were 9.4 mm Hg and 37.1 days (P<0.0001), respectively, with the combination regimen. The maximum dose regimen decreased home SBP with a very gentle slope, and estimated maximal effect and estimated stabilization time were not significant (P>0.2). The rate of achieving target BP (home morning SBP <135 mm Hg) was significantly higher with the combination regimen than with the maximum dose regimen (52.4 vs. 30.1%, P=0.002). In conclusion, changing from 8 mg candesartan to combination therapy was more effective in reducing home SBP and achieving goal BP more rapidly than increasing the candesartan dose.
Efficacy of Low-Dose Chlorthalidone and Hydrochlorothiazide as Assessed by 24-h Ambulatory Blood Pressure Monitoring.
Pareek Anil K,Messerli Franz H,Chandurkar Nitin B,Dharmadhikari Shruti K,Godbole Anil V,Kshirsagar Prasita P,Agarwal Manish A,Sharma Kamal H,Mathur Shyam L,Kumbla Mukund M
Journal of the American College of Cardiology
BACKGROUND:Thiazide and thiazide-like diuretic agents are being increasingly used at lower doses. Hydrochlorothiazide (HCTZ) in the 12.5-mg dose remains the most commonly prescribed antihypertensive agent in the United States. OBJECTIVES:This study compared chlorthalidone, 6.25 mg daily, with HCTZ, 12.5 mg daily, by 24-h ambulatory blood pressure (ABP) monitoring and evaluated efficacy. Because HCTZ has been perceived as a short-acting drug, a third comparison with an extended-release formulation (HCTZ-controlled release [CR]) was added. METHODS:This 12-week comparative, double-blind, outpatient study randomized 54 patients with stage 1 hypertension to receive either chlorthalidone, 6.25 mg, (n = 16); HCTZ 12.5 mg (n = 18); or HCTZ-CR 12.5 mg (n = 20). ABP monitoring was performed at baseline and after 4 and 12 weeks of therapy. RESULTS:All 3 treatments significantly (p < 0.01) lowered office BP at weeks 4 and 12 from baseline. At weeks 4 and 12, significant reductions in systolic and diastolic 24-h ambulatory and nighttime BP (p < 0.01) were observed with chlorthalidone but not with HCTZ. At weeks 4 (p = 0.015) and 12 (p = 0.020), nighttime systolic ABP was significantly lower in the chlorthalidone group than in the the HCTZ group. With HCTZ therapy, sustained hypertension was converted into masked hypertension. In contrast to the HCTZ group, the HCTZ-CR group also showed a significant (p < 0.01) reduction in 24-h ABP. All 3 treatments were generally safe and well tolerated. CONCLUSIONS:Treatment with low-dose chlorthalidone, 6.25 mg daily, significantly reduced mean 24-h ABP as well as daytime and nighttime BP. Due to its short duration of action, no significant 24-h ABP reduction was seen with HCTZ, 12.5 mg daily, which merely converted sustained hypertension into masked hypertension. Thus, low-dose chlorthalidone, 6.25 mg, could be used as monotherapy for treatment of essential hypertension, whereas low-dose HCTZ monotherapy is not an appropriate antihypertensive drug. (Comparative Evaluation of Safety and Efficacy of Hydrochlorothiazide CR with Hydrochlorothiazide and Chlorthalidone in Patients With Stage I Essential Hypertension; CTRI/2013/07/003793).
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.
Efficacy and Safety of Fixed-Dose Perindopril Arginine/Amlodipine in Hypertensive Patients Not Adequately Controlled with Amlodipine 5 mg or Perindopril tert-Butylamine 4 mg Monotherapy.
Hu Dayi,Sun Yihong,Liao Yuhua,Huang Jing,Zhao Ruiping,Yang Kan
OBJECTIVES:To assess the blood pressure-lowering efficacy and tolerability of perindopril/amlodipine fixed-dose combinations in Chinese patients with mild-to-moderate essential hypertension not adequately controlled with monotherapy alone. METHODS:In 2 separate double-blind studies, patients received a 4-week run-in monotherapy of amlodipine 5 mg or perindopril 4 mg, respectively. Those whose blood pressure was uncontrolled were then randomized to receive the fixed-dose combination of perindopril 5 mg/amlodipine 5 mg (Per/Amlo group) or remain on the monotherapy for 8 weeks. Patients who were uncontrolled at the week 8 (W8) visit were up-titrated for the Per/Amlo combination, or received additional treatment if on monotherapy, for a further 4 weeks. The main efficacy assessment was at 8 weeks. RESULTS:After 8 weeks, systolic blood pressure (SBP; primary criterion) was statistically significantly lower in the Per/Amlo group (vs. Amlo 5 mg, p = 0.0095; vs. Per 4 mg, p < 0.0001). Uncontrolled patients at W8 who received an up-titration of the Per/Amlo combination showed a further SBP reduction. These changes were mirrored by reassuring reductions in diastolic blood pressure. The fixed-dose combinations were well tolerated. CONCLUSIONS:Single-pill combinations of perindopril and amlodipine provide hypertensive patients with a convenient and effective method of reducing blood pressure.
Relationship between initial therapy and blood pressure control for high-risk hypertension patients in the UK: a retrospective cohort study from the THIN general practice database.
Weir Sharada,Juhasz Attila,Puelles Jorge,Tierney Travis S
OBJECTIVE:To examine the UK practice patterns in treating newly diagnosed hypertension and to determine whether subgroups of high-risk patients are more or less likely to follow particular therapeutic protocols and to reach blood pressure goals. DESIGN:Retrospective cohort study. SETTING:This study examined adults in The Health Improvement Network (THIN) UK general practice medical records database who were initiated on medication for hypertension. PARTICIPANTS:48 131 patients with essential hypertension diagnosed between 2008 and 2010 who were registered with a participating practice for a minimum of 13 months prior to, and 6 months following, initiation of therapy. We excluded patients with gestational hypertension or secondary hypertension. Patients were classified into risk groups based on blood pressure readings and comorbid conditions. PRIMARY AND SECONDARY OUTCOME MEASURES:Odds of receiving single versus fixed or free-drug combination therapy and odds of achieving blood pressure control were assessed using multivariable logistic regression. RESULTS:The vast majority of patients (95.8%) were initiated on single drug therapy. Patients with high cardiovascular risk (patients with grade 2-3 hypertension or those with high normal/grade 1 hypertension plus at least one cardiovascular condition pretreatment) had a statistically significant benefit of starting immediately on combination therapy when blood pressure control was the desired goal (OR: 1.23; 95% CI: 1.06 to 1.42) but, surprisingly, were less likely than patients with no risk factors to receive combination therapy (OR: 0.53; 95% CI: 0.47 to 0.59). CONCLUSIONS:Our results suggest that combination therapy may be indicated for patients with high cardiovascular risk, who accounted for 60.6% of our study population. The National Institute for Health and Care Excellence guideline CG34 of 2006 (in effect during the study period) recommended starting with single drug class therapy for most patients, and this advice does seem to have been followed even in cases where a more aggressive approach might have been considered.
[One year adherence of ramipril versus ramipril/amlodipine fixed dose combination therapy in hypertension].
Simonyi Gábor,Ferenci Tamás
INTRODUCTION:In the treatment of hypertension avoiding adverse cardiovascular complications to achieve target blood pressure is essential. The appropriate drug selection, and if necessary to change to combination therapy, patients adherence is important which may help fixed dose combination. AIM:The aim of the authors was to investigate the one year adherence of the ramipril and ramipril/amlodipine fixed dose combination in hypertensive patients. METHOD:Prescriptions database of the National Health Insurance Fund in Hungary on pharmacy-claims was analysed between October 1, 2012 and September 30, 2013. The authors identified patients who filled prescriptions for ramipril monotherapy and fixed dose combinations of ramipril/amlodipine prescribed for the first time in hypertensive patients who have not received similar drugs in the previous year. To model the adherence, the apparatus of survival analysis was used, where "survival" was the time to abandon the medication. As it was available to month precision, discrete time survival analysis was applied: a generalized linear model was estimated with complementary log-log link function with the kind of drug being the only explanatory variable. RESULTS:92,546 patients met the inclusion criteria. During the trial period, ramipril therapy or ramipril/amlodipine fixed dose combination was started in 82,251 and 10,295 patients, respectively. One year persistence rate in patients with ramipril was 30% and 54% in patients with ramipril/amlodipine fixed dose combination therapy. Considering only the 360-day study period, the mean duration of persistence was 189.9 days in patients on ramipril and 270.6 days on ramipril/amlodipine fixed dose combination therapy. The hazard of discontinuation was more than twofold higher during treatment with ramipril compared with the use of the ramipril/amlodipine fixed dose combination therapy (HR = 2.11 [95% CI: 2.05-2.17], p<0,001). CONCLUSIONS:There is a significant difference between the one year persistence of ramipril and ramipril/amlodipine fixed dose combination therapy in hypertension. The result demonstrated that ramipril/amlodipine fixed dose combination therapy has a better one year persistence rate. When the next step is necessary to achieve target blood pressure, ramipril/amlodipine fixed dose combination therapy is preferable. Orv Hetil. 2017; 158(42): 1668-1673.
[Status analysis of patients with hypertension in 22 community health centers of Shenzhen Futian District].
Xu W M,Zhang X X,Wu G F
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences
OBJECTIVE:To investigate current situation of blood pressure control in patients with hypertension in 22 community health centers of Shenzhen Futian District, and to find out related factors which affect blood pressure control. METHODS:In the study, 10 020 cases with essential hypertension that had been registered in 22 Community Health Centers were selected as cases for the survey. The questionnaires, physical examinations, and laboratory tests were used to obtain the patients' baseline data. RESULTS:The mean blood pressure (median) levels were 142/86 mmHg (1 mmHg=0.133 kPa). Those of the males were higher than those of the females (142/86 mmHg vs. 140/85 mmHg, ZSBP=-6.14,ZDBP=-9.93,P<0.001), the systolic blood pressure increased with age. The overall blood pressure control rate was 40.2%. The blood control rates were different with different gender, body mass index (BMI) and waist circumference. The majority of the patients took single antihypertensive drug, and the proportion accounted to 54.4%. Regression analysis showed that gender, age, hyperlipidemia, smoking, and waist circumference were the main factors that affected blood pressure control. CONCLUSION:The blood control rate was low in these communities. Patients with high blood pressure often merge a variety of factors that affect blood pressure control, and at the same time of antihypertensive therapy for the patients, we should pay attention to the control of these factors.
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.
The effects of a low-salt diet on the efficacy of different antihypertensive drug regimens.
Wang Jing,Qiu Bo,Du Jian-Lin,Deng Song-Bai,Liu Ya-Jie,She Qiang
Journal of clinical pharmacology
The objective of this study was to compare the antihypertensive effects of 3 types of antihypertensive drug regimens between different salt intake levels. The 180 patients with mild to moderate primary hypertension participating in this randomized, controlled clinical trial were randomly allocated to a low-salt diet (LSD) group or a non-low-salt diet (NLSD) group. Each group included 3 subgroups: a losartan 100 mg subgroup, a losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg subgroup, and an irbesartan 150 mg/HCTZ 12.5 mg subgroup. The LSD group received a diet in which the sodium content was strictly controlled (2.3 g/day). After 2 months, the office blood pressure (BP), the 24-hour mean BP, and the morning BP were significantly reduced (P ≤ .01) in each group. No significant differences were observed between the 3 LSD subgroups (P > .05). In the NLSD group, the losartan 50 mg/HCTZ 12.5 mg subgroup, and the irbesartan 150 mg/HCTZ 12.5 mg subgroup exhibited identical antihypertensive efficacy (P > .05), and these groups were significantly different from the losartan 100 mg subgroup(P ≤ .05). The BP of the patients who received the LSD was further decreased compared with those who received the NLSD (P ≤ .05). Therefore, we concluded that this LSD exerts synergistic BP-reducing effects.
Blood pressure lowering efficacy of dual alpha and beta blockers for primary hypertension.
Wong Gavin W K,Laugerotte Alexandra,Wright James M
The Cochrane database of systematic reviews
BACKGROUND:Drugs with combined alpha and beta blocking activity are commonly prescribed to treat hypertension. However, the blood pressure (BP) lowering efficacy of this class of beta blockers has not been systematically reviewed and quantified. OBJECTIVES:To quantify the dose-related effects of various types of dual alpha and beta adrenergic receptor blockers (dual receptor blockers) on systolic and diastolic blood pressure versus placebo in patients with primary hypertension. SEARCH METHODS:We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ClinicalTrials.gov for randomized controlled trials up to October 2014. The WHO International Clinical Trials Registry Platform (ICTRP) is searched for inclusion in the Group's Specialised Register. SELECTION CRITERIA:Randomized double blind placebo controlled parallel or cross-over trials. Studies contained a beta blocker monotherapy arm with a fixed dose. Patients enrolled in the studies had primary hypertension at baseline. Duration of the studies was from three to 12 weeks. Drugs in this class of beta blockers are carvedilol, dilevalol and labetalol. DATA COLLECTION AND ANALYSIS:Two review authors (GW and AL) confirmed the inclusion of studies and extracted the data independently. RevMan 5.3 was used to synthesize data. MAIN RESULTS:We included eight studies examining the blood pressure lowering efficacy of carvedilol and labetalol in 1493 hypertensive patients. Five of the included studies were parallel design; three were cross-over design. The two largest included studies were unpublished carvedilol studies. The estimates of BP lowering effect (systolic BP/diastolic BP millimeters of mercury; SPB/DBP mm Hg) were -4 mm Hg (95% confidence intervals (CI) -6 to -2)/-3 mm Hg (95% CI -4 to -2) for carvedilol (>1000 subjects) and -10 mm Hg (95% CI -14 to -7)/-7 mm Hg (95% CI -9 to -5) for labetalol (110 subjects). The effect of labetalol is likely to be exaggerated due to high risk of bias. Carvedilol, within the recommended dose range, did not show a significant dose response effect for SBP or DBP. Carvedilol had little or no effect on pulse pressure (-1 mm Hg) and did not change BP variability. Overall, once and twice the starting dose of carvedilol and labetalol lowered BP by -6 mm Hg (95% CI -7 to -4) /-4 mm Hg (95% CI -4 to -3) (low quality evidence) and lowered heart rate by five beats per minute (95% CI -6 to -4) (low quality evidence). Five studies (N = 1412) reported withdrawal due to adverse effects; the risk ratio was 0.88 (95% CI 0.54 to 1.42) (moderate quality evidence). AUTHORS' CONCLUSIONS:This review provides low quality evidence that in patients with mild to moderate hypertension, dual receptor blockers lowered trough BP by an average of -6/-4 mm Hg and reduced heart rate by five beats per minute. Due to the larger sample size from the two unpublished studies, carvedilol provided a better estimate of BP lowering effect than labetalol. The BP lowering estimate from combining carvedilol once and twice the starting doses is -4/-3 mm Hg. Doses higher than the recommended starting dose did not provide additional BP reduction. Higher doses of dual receptor blockers caused more bradycardia than lower doses. Based on indirect comparison with other classes of drugs, the blood pressure lowering effect of dual alpha- and beta-receptor blockers is less than non-selective, beta1 selective and partial agonist beta blockers, as well as thiazides and drugs inhibiting the renin angiotensin system. Dual blockers also had little or no effect on reducing pulse pressure, which is similar to the other beta-blocker classes, but less than the average reduction of pulse pressure seen with thiazides and drugs inhibiting the renin angiotensin system. Patients taking dual receptor blockers were not more likely to withdraw from the study compared to patients taking placebo.
Efficacy and safety of valsartan/amlodipine single-pill combination in patients with essential hypertension (PEAK LOW).
Kızılırmak Pınar,Ar Idilhan,Ilerigelen Barış
Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir
OBJECTIVES:This study evaluated the efficacy as well as the safety and tolerability profile of low-dose valsartan/amlodipine (Val/Amlo) single-pill combination (SPC) (160/5 mg) in patients with essential hypertension in Turkey. STUDY DESIGN:Adult patients with essential hypertension [systolic blood pressure (SBP)>140 mmHg and/or diastolic blood pressure (DBP)>90 mmHg], who were on low dose Val/Amlo (160/5 mg) SPC before enrollment and gave informed consent, were accepted for this multi-centric observational study performed at 30 sites. The absolute changes in SBP and DBP from baseline were the primary efficacy outcomes. Safety assessments consisted of recording all adverse events. RESULTS:Of 381 patients enrolled, 327 completed the study; 39% were females. The mean age was 57.3±11.8 years. Median duration of hypertension was 38 months. Both SBP and DBP values showed reductions from 162.6±16.6 mmHg and 94.0±13.2 mmHg to 137.6±14.2 mmHg and 81.9±9.0 mmHg at 4th week and to 131.6±11.5 mmHg and 79.7±7.6 mmHg at 12th week, respectively. The control and response rates at the end of the study were 82.0% and 92.6%, respectively. Twelve patients (3.2%) experienced a total of 12 adverse events; there were no serious adverse events. The most common adverse event was edema (1.3%). Patient compliance was approximately 99%. CONCLUSION:Low-dose (160/5 mg) Val/Amlo SPC is efficacous and has a good tolerability and safety profile for the management of essential hypertension in Turkey.
Effects of triple combination therapy with azilsartan/amlodipine/hydrochlorothiazide on office/home blood pressure: a randomized-controlled trial in Japanese essential hypertensive patients.
Rakugi Hiromi,Shimizu Kohei,Sano Yuhei,Nishiyama Yuya,Kinugawa Yoshinobu,Terashio Souhei
Blood pressure monitoring
OBJECTIVE:The efficacy and safety of triple therapy with azilsartan (AZI), amlodipine besylate (AML), and hydrochlorothiazide (HCTZ) compared with dual therapy with AZI/AML or HCTZ monotherapy were evaluated in Japanese essential hypertensive patients in a double-blinded manner. PATIENTS AND METHODS:A total of 353 patients with office blood pressure (BP) of at least 150/95 mmHg were randomized to a 10-week treatment with AZI/AML/HCTZ 20/5/12.5 mg, AZI/AML/HCTZ 20/5/6.25 mg, AZI/AML 20/5 mg, HCTZ 12.5 mg, or HCTZ 6.25 mg. RESULTS:The mean change from baseline in office diastolic/systolic BPs at week 10 was -25.9/-41.4, -24.9/-38.6, and -22.4/-34.5 mmHg in the AZI/AML/HCTZ 20/5/12.5 mg, AZI/AML/HCTZ 20/5/6.25 mg, and AZI/AML 20/5 mg groups, respectively. AZI/AML/HCTZ 20/5/12.5 mg led to a significantly greater reduction in diastolic and systolic BP than the dual therapy. In addition, the change in home diastolic BP measured with telemetry devices showed a significant difference between the two triple therapy groups. The incidences of adverse events except dizziness postural were similar among the treatment groups in the triple therapy groups. CONCLUSION:Triple therapy with AZI/AML/HCTZ 20/5/12.5 mg shows a greater antihypertensive effect than the dual therapy and has acceptable safety profiles for Japanese essential hypertensive patients. It was also observed that home BP measurement by automated telemetry could detect changes in BP that were not detected in office BP measurement, although further investigation is needed.
Efficacy and Tolerability of Antihypertensive Drugs in Diabetic and Nondiabetic Patients.
Aslam Maria,Ahmad Mobasher,Mobasher Fizza
Journal of pharmacy & bioallied sciences
OBJECTIVES OF THE STUDY:The aim of the study was to compare the efficacy and tolerability of different classes of antihypertensive drugs in diabetic and nondiabetic patients (NDPs) with essential hypertension. MATERIAL AND METHODS:The study was conducted in Mayo Hospital, Punjab Institute of Cardiology, and National Defence Hospital, Lahore, Pakistan, on 200 hypertensive patients with diabetes and 230 hypertensive patients without (Three hospitals) diabetes. Both male and female patients of age between 30 and 80 years with systolic blood pressure (SBP) above 130 mmHg and diastolic blood pressure (DBP) above 80 mmHg were enrolled in the study. Angiotensin converting enzyme inhibitors (ACEI), beta-blocker (βB), calcium-channel blocker (CCB), diuretics (D), angiotensin receptor blocker (ARB) as well as α-blocker classes of antihypertensive drugs were used. These drugs were used as monotherapy as well as combination therapy. The study was conducted for 4 months (July-October). After 4 months, patients were assessed for efficacy by monitoring blood pressure (BP) and tolerability by assessing safety profile on renal function, liver function as well as lipid profile. RESULTS:Significant control in mean BP by all drug groups was observed in "both groups that is patients with diabetes and without diabetes." The efficacy and tolerability data revealed that in diabetic patients with hypertension, the highest decrease in SBP and DBP was observed using monotherapy with ACEI, two-drug combination therapy with ACEI plus diuretic, ARBs plus diuretic, ACEI plus CCBs, three-drug combination therapy with ACEI plus CCBs plus diuretic, and four drug combination therapy with ACEI plus CCBs plus diuretic plus βBs, ARB's plus CCBs plus diuretic plus βBs while in NDPs, monotherapy with diuretic, two-drug combination therapy with ACEI plus CCBs, ACEI plus βBs, three-drug combination therapy with βBs plus ACEI plus D was found more effective in controlling SBP as well as DBP. Adverse effects observed were dry cough, pedal edema, dizziness, muscular cramps, constipation, palpitations, sweating, vertigo, tinnitus, paresthesia, and sexual dysfunction. CONCLUSION:All classes of antihypertensives were found to control blood pressure significantly in both groups of patients that is diabetic patients with hypertesion and non-diabetic patients with 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.
Comparison of efficacy and safety between two different irbesartan, generic vs branded, in the treatment of Korean patients with mild-to-moderate hypertension: an 8-week, multicenter, randomized, open-label, Phase IV clinical study.
Han Seung Hwan,Oh Gyu Chul,Kwon Hyuck Moon,Park Chang Gyu,Kim In Jai,Hwang Gyo-Seung,Yoo Byung Su,Park Seong Hoon,Lee Kwang Je,Kim Hyo-Soo
Drug design, development and therapy
Purpose:This study aimed to compare the efficacy and safety of generic and branded irbesartan for 8 weeks in patients with mild-to-moderate essential hypertension. Patients and methods:We screened 221 patients with mild-to-moderate hypertension. After exclusion per study criteria, 177 subjects were randomized to receive 150 mg generic irbesartan (n=91) or branded irbesartan (n=86) as the intention to treat set. The primary efficacy endpoint of this study was the change in mean sitting diastolic blood pressure (SiDBP) from baseline to 8 weeks between the generic and branded irbesartan groups. The secondary efficacy endpoints were the change in mean SiDBP at Week 4 from baseline and the change in mean sitting systolic blood pressure (SiSBP) at Weeks 4 and 8 from baseline in both groups. All safety issues were evaluated. Results:At Week 8, the generic and branded irbesartan groups showed significantly reduced SiDBP (-10.3±8.0, -10.7±7.7 mmHg, all <0.0001) compared with baseline values, and the mean between-group difference in SiDBP change after 8 weeks of treatment was -0.4±1.2 mmHg, showing the non-inferiority of generic irbesartan vs branded irbesartan. Furthermore, secondary efficacy, which was the mean change of SiDBP from baseline at 4 weeks, was comparable between the two groups (-9.4±8.1 vs -9.9±7.4 mmHg, =0.69). There were no between-group differences in mean changes of SiSBP after 4 or 8 weeks of treatment (=0.78, =0.97, respectively), or in the incidence of adverse effects (16.7 vs 24.4%, =0.20). Conclusion:Generic irbesartan treatment in patients with mild-to-moderate essential hypertension has shown effective antihypertensive effects comparable with the branded irbesartan treatment, with similar incidence of adverse effects.
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.
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.
[The effects of olmesartan on ambulatory blood pressures and blood pressure variability in patients with mild to moderate essential hypertension].
Li Jing,Qin Tingli,Jiang Hong,Wang Hao,Ke Yuannan
Zhonghua nei ke za zhi
OBJECTIVE:To evaluate the effect of olmesartan medoxomil tablets (olmesartan) in comparison with Olmetec on 24 h ambulatory blood pressure (ABPM) and blood pressure variability (BPV) in patients with mild to moderate hypertension. METHODS:A randomized, double-blind, double-mimic controlled trial was performed.Forty-eight patients with mild to moderate essential hypertension were randomly into treatment group (olmesartan) and control group (Olmetec) for eight weeks. The ABPM was taken before and at the end of the trial. RESULTS:After eight weeks, treatment with olmesartan induced a significant reduction in ABPM in patients [(9 ± 3)/(11 ± 3) mmHg(1 mmHg = 0.133 kPa)], which is similar with the reduction by Olmetec [(9 ± 4)/(9 ± 5) mmHg], P > 0.05. This situation holds for BPV with the standard deviations of 24 h, systolic blood pressure/diastolic blood pressure of pre-treatment and pro-treatment were (10 ± 2)/(11 ± 3) mmHg vs (10 ± 3)/(12 ± 2) mmHg in olmesartan group, and (10 ± 3)/(11 ± 3) mmHg vs (12 ± 3)/(12 ± 4) mmHg in Olmetec group. (3) There is no difference in the rate of adverse event between olmesartan (10.42%) and Olmetec (8.33%) treatment (P > 0.05). CONCLUSION:Similar to Olmetec, treatment with olmesartan once daily can significantly reduce ABPM in patients with mild to moderate essential hypertension.
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.
A Randomized, Multicenter, Double-blind, Placebo-controlled, 3 × 3 Factorial Design, Phase II Study to Evaluate the Efficacy and Safety of the Combination of Fimasartan/Amlodipine in Patients With Essential Hypertension.
Lee Hae-Young,Kim Yong-Jin,Ahn Taehoon,Youn Ho-Joong,Chull Chae Shung,Seog Seo Hong,Kim Ki-Sik,Rhee Moo-Yong,Choi Dong-Ju,Kim Jae-Joong,Chun Kook-Jin,Yoo Byung-Su,Park Jong-Seon,Oh Seok-Kyu,Kim Dong-Soo,Kwan Jun,Ahn Youngkeun,Bae Park Jeong,Jeong Jin-Ok,Hyon Min-Soo,Cho Eun-Joo,Han Kyoo-Rok,Kim Doo-Il,Joo Seung-Jae,Shin Jin-Ho,Sung Ki-Chul,Jeon Eun-Seok
PURPOSE:The objective of this study was to evaluate the efficacy and safety of a fimasartan/amlodipine combination in patients with hypertension and to determine the optimal composition for a future single-pill combination formulation. METHODS:This Phase II study was conducted by using a randomized, multicenter, double-blind, placebo-controlled, 3 × 3 factorial design. After a 2-week placebo run-in period, eligible hypertensive patients (with a sitting diastolic blood pressure [SiDBP] between 90 and 114 mm Hg) were randomized to treatment. They received single or combined administration of fimasartan at 3 doses (0, 30, and 60 mg) and amlodipine at 3 doses (0, 5, and 10 mg) for 8 weeks. The primary efficacy end point was the change in SiDBP from baseline and at week 8; secondary end points included the change in SiDBP from baseline and at week 4 and the changes in sitting systolic blood pressure from baseline and at weeks 4 and 8. Treatment-emergent adverse events (AEs) were also assessed. FINDINGS:420 Korean patients with mild to moderate hypertension were randomly allocated to the 9 groups. Mean (SD) SiDBP changes in each group after 8 weeks were as follows: placebo, -6.0 (8.5) mm Hg; amlodipine 5 mg, -10.6 (9.2) mm Hg; amlodipine 10 mg, -15.9 (7.2) mm Hg; fimasartan 30 mg, -10.1 (9.1) mm Hg; fimasartan 60 mg, -13.0 (10.0) mm Hg; fimasartan 30 mg/amlodipine 5 mg, -16.2 (8.5) mm Hg; fimasartan 30 mg/amlodipine 10 mg, -19.5 (7.5) mm Hg; fimasartan 60 mg/amlodipine 5 mg, -16.6 (6.9) mm Hg; and fimasartan 60 mg/amlodipine 10 mg, -21.5 (8.3) mm Hg. All treatment groups produced significantly greater reductions in blood pressure compared with the placebo group. In addition, all combination treatment groups had superior reductions in blood pressure compared with the monotherapy groups. In the combination treatment groups, doubling fimasartan dose in the given dose of amlodipine did not show further BP reduction, whereas doubling amlodipine dose showed significantly further BP reduction in the given dose of fimasartan. During the study period, 75 (17.9%) of 419 patients experienced 110 AEs. Ninety-five AEs were mild, 9 were moderate, and 6 were severe in intensity. Eight patients discontinued the study due to AEs. There was no significant difference in incidence of AEs among groups (P = 0.0884). The most common AE was headache (12 patients [2.9%]), followed by dizziness (11 patients [2.6%]) and elevated blood creatine phosphokinase levels (6 patients [1.4%]). IMPLICATIONS:Fimasartan combined with amlodipine produced superior blood pressure reductions and low levels of AEs compared with either monotherapy. Therefore, a single-pill combination with fimasartan 60 mg/amlodipine 10 mg will be developed. ClinicalTrials.gov: NCT01518998.
Efficacy and safety evaluation of perindopril-lercanidipine combined therapy in patients with mild essential hypertension.
Current medical research and opinion
OBJECTIVE:To investigate the efficacy and safety of perindopril-lercanidipine combination versus perindopril or lercanidipine monotherapies in patients with mild essential hypertension. METHODS:A total of 180 patients with mild essential hypertension were randomly assigned to three groups: group A (perindopril 2 mg plus lercanidipine 5 mg; n = 60), group B (lercanidipine 10 mg; n = 60) and group C (perindopril 4 mg; n = 60). The treatment efficacy and the incidence of adverse events were evaluated at the end of 4, 8 and 12 weeks after treatment initiation. RESULTS:The blood pressure in group A was already lower than in group B and group C at week 4 after treatment initiation. Systolic blood pressure was 148 ± 13 mmHg in group A, 151 ± 14 mmHg in group B, and 153 ± 13 in group C (p < 0.001); diastolic blood pressure was 89 ± 8, 92 ± 7 and 92 ± 6 mmHg, respectively (p < 0.001). At the end of treatment the normalization rate was significantly higher in group A, compared with group B and group C (71.7%, 68.3%, and 48.3%, respectively; p < 0.05). Four adverse events were observed in group A, while seven and nineteen adverse events occurred in group B and in group C, respectively. Statistically significant differences in adverse reaction incidence were reported among three groups. CONCLUSION:Although its results were collected in an overall limited number of patients in a single center, this study shows that the combination of perindopril and lercanidipine, compared with lercanidipine alone or perindopril alone, was effective in improving blood pressure in mild essential hypertensive patients, and also decreased the incidence of adverse events.
Long-term safety and efficacy of high-dose controlled-release nifedipine (80 mg per day) in Japanese patients with essential hypertension.
Shimamoto Kazuaki,Kimoto Masafumi,Matsuda Yoshimi,Asano Kozue,Kajikawa Mariko
Hypertension research : official journal of the Japanese Society of Hypertension
High-dose calcium channel blocker (CCB) shows strong blood pressure (BP) lowering effect. Currently available of controlled-release (CR) nifedipine 80 mg per day clinical data are limited to monotherapy and short-term or long-term retrospective studies. We report the safety and efficacy results of a 52-week, prospective open-label study, in which Japanese patients with essential hypertension were treated with CR nifedipine [80 mg per day; 40 mg bis in die (BID; twice daily)] in combination with other antihypertensive drugs. The patients with inadequate BP control despite treatment with CR nifedipine (40 mg once daily) in combination with other antihypertensive drugs were enrolled. The primary objective of this study was to assess the long-term safety of CR nifedipine (80 mg per day). Efficacy variables included changes in the mean sitting BP, the target BP achievement rate and the BP response rate. CR nifedipine (80 mg per day) was generally well tolerated, with the most common drug-related treatment-emergent adverse event being tachycardia (6.9% of patients). Serious treatment-emergent adverse events were reported in three (4.2%) patients. By week 52, the mean reductions in sitting systolic and diastolic BP were 19.4 and 13.6 mm Hg, respectively. The target BP achievement and BP response rates after 52 weeks of treatment were 32.4 and 63.4%, respectively. Based on these findings, long-term treatment with CR nifedipine at 40 mg BID in combination with antihypertensive drugs was well tolerated and effective in Japanese patients with essential hypertension.
Effect of azilsartan versus candesartan on morning blood pressure surges in Japanese patients with essential hypertension.
Rakugi Hiromi,Kario Kazuomi,Enya Kazuaki,Sugiura Kenkichi,Ikeda Yoshinori
Blood pressure monitoring
Morning blood pressure (BP) surge is reported as a risk factor for cardiovascular events and end-organ damage independent of the 24-h BP level. Controlling morning BP surge is therefore important to help prevent onset of cardiovascular disease. We compared the efficacy of azilsartan and candesartan in controlling morning systolic BP (SBP) surges by analyzing relevant ambulatory BP monitoring data in patients with/without baseline BP surges. As part of a 16-week randomized, double-blind study of azilsartan (20-40 mg once daily) and candesartan (8-12 mg once daily) in Japanese patients with essential hypertension, an exploratory analysis was carried out using ambulatory BP monitoring at baseline and week 14. The effects of study drugs on morning BP surges, including sleep trough surge (early morning SBP minus the lowest night-time SBP) and prewaking surge (early morning SBP minus SBP before awakening), were evaluated. Patients with sleep trough surge of at least 35 mmHg were defined by the presence of a morning BP surge (the 'surge group'). Sleep trough surge and prewaking surge data were available at both baseline and week 14 in 548 patients, 147 of whom (azilsartan 76; candesartan 71) had a baseline morning BP surge. In surge group patients, azilsartan significantly reduced both the sleep trough surge and the prewaking surge at week 14 compared with candesartan (least squares means of the between-group differences -5.8 mmHg, P=0.0395; and -5.7 mmHg, P=0.0228, respectively). Once-daily azilsartan improved sleep trough surge and prewaking surge to a greater extent than candesartan in Japanese patients with grade I-II essential hypertension.
Effects of aqueous extract of Hibiscus sabdariffa on the renin-angiotensin-aldosterone system of Nigerians with mild to moderate essential hypertension: A comparative study with lisinopril.
Nwachukwu Daniel Chukwu,Aneke Eddy Ikemefuna,Obika Leonard Fidelis,Nwachukwu Nkiru Zuada
Indian journal of pharmacology
OBJECTIVES:The present study investigated the effects of aqueous extract of Hibiscus sabdariffa (HS) on the three basic components of renin-angiotensin-aldosterone system: Plasma renin, serum angiotensin-converting enzyme (ACE), and plasma aldosterone (PA) in mild to moderate essential hypertensive Nigerians and compared with that of lisinopril, an ACE inhibitor. MATERIALS AND METHODS:A double-blind controlled randomized clinical study was used. Seventy-eight newly diagnosed but untreated mild to moderate hypertensive subjects attending Medical Outpatients Clinic of Enugu State University Teaching Hospital, Enugu were recruited for the study. Those in Group A received placebo (150 mg/kg/day), Group B were given lisinopril (10 mg once daily) while those in Group C received aqueous extract of HS (150 mg/kg/day). After 4 weeks of treatment, the levels of plasma renin, serum ACE, and PA were determined. RESULTS:HS and lisinopril significantly (P < 0.001) reduced PA compared to placebo by 32.06% and 30.01%, respectively. Their effects on serum ACE and plasma renin activity (PRA) were not significant compared to placebo; they reduced ACE by 6.63% and 5.67% but increased plasma PRA by 2.77% and 5.36%, respectively. CONCLUSION:HS reduced serum ACE and PA in mild to moderate hypertensive Nigerians with equal efficacy as lisinopril. These actions are possibly due to the presence of anthocyanins in the extract.
Evaluation of the Efficacy and Safety of the Lercanidipine/Valsartan Combination in Korean Patients With Essential Hypertension Not Adequately Controlled With Lercanidipine Monotherapy: A Randomized, Multicenter, Parallel Design, Phase III Clinical Trial.
Na Sang-Hoon,Lee Hae-Young,Hong Baek Sang,Jeon Hui-Kyung,Kang Jin-Ho,Kim Yoon-Nyun,Park Chang-Gyu,Ryu Jae-Kean,Rhee Moo-Yong,Kim Moo-Hyun,Hong Taek-Jong,Choi Dong-Ju,Cho Seong-Wook,Cha Dong-Hun,Jeon Eun-Seok,Kim Jae-Joong,Shin Joon-Han,Park Sung-Ha,Lee Seung-Hwan,John Sung-Hee,Shin Eun-Seok,Kim Nam-Ho,Lee Sung-Yun,Kwan Jun,Jeong Myung-Ho,Kim Sang-Wook,Jeong Jin-Ok,Kim Dong-Woon,Lee Nam-Ho,Park Woo-Jung,Ahn Jeong-Cheon,Won Kyung-Heon,Uk Lee Seung,Cho Jang-Hyun,Kim Soon-Kil,Ahn Taehoon,Hong Sukkeun,Yoo Sang-Yong,Kim Song-Yi,Kim Byung-Soo,Juhn Jae-Hyeon,Kim Sun-Young,Lee Yu-Jeong,Oh Byung-Hee
PURPOSE:The objective of this study was to evaluate the efficacy and safety of the lercanidipine/valsartan combination compared with lercanidipine monotherapy in patients with hypertension. METHODS:Part 1 of this study was the randomized, multicenter, double-blind, parallel group, Phase III, 8-week clinical trial to compare superiority of lercanidipine 10 mg/valsartan 80 mg (L10/V80) and lercanidipine 10 mg/valsartan 160 mg (L10/V160) combinations with lercanidipine 10 mg (L10) monotherapy. At screening, hypertensive patients, whose diastolic blood pressure (DBP) was >90 mm Hg after 4 weeks with L10, were randomized to 3 groups of L10, L10/V80, and L10/V160. The primary end point was the change in the mean sitting DBP from baseline (week 0) after 8 weeks of therapy. Patients who were randomly assigned to L10/V160 and whose mean DBP was still ≥ 90 mm Hg in part 1 were enrolled to the up-titration extension study with lercanidipine 20 mg/valsartan 160 mg (L20/V160) (part 2). FINDINGS:Of 772 patients screened, 497 were randomized to 3 groups (166 in the L10 group, 168 in the L10/V80 group, and 163 in the L10/V160 group). Mean (SD) age was 55 (9.9) years, and male patients comprised 69%. The mean (SD) baseline systolic blood pressure (SBP)/DBP were 148.4 (15.1)/94.3 (9.5) mm Hg. No significant differences were found between groups in baseline characteristics except the percentages of previous history of antihypertensive medication. The primary end points, the changes of mean (SD) DBP at week 8 from the baseline were -2.0 (8.8) mm Hg in the L10 group, -6.7 (8.5) mm Hg in L10/V80 group, and -8.1 (8.4) mm Hg in L10/V160 group. The adjusted mean difference between the combination groups and the L10 monotherapy group was -4.6 mm Hg (95% CI, -6.5 to -2.6; P < 0.001) in the L10/V80 group and -5.9 mm Hg (95% CI, -7.9 to -4.0, P < 0.001) in the L10/V160 group, which had significantly greater efficacy in BP lowering. A total of 74 patients were enrolled in the part 2 extension study. Changes of mean (SD) DBP and SBP from week 8 to week 12 and week 16 were -5.6 (7.9)/-8.0 (12.0) mm Hg and -5.5 (7.0)/-8.5 (11.3) mm Hg, respectively. For evaluation of the safety profile, the frequencies of adverse events between groups were also not significantly different. The most frequently reported adverse events were headache (6 cases, 20.7%) in the L10 group, dizziness (8 cases, 16.3%) in L10/V80 group, and nasopharyngitis (3 cases, 9.4%) in L10/V160 group, and the incidences of adverse events were not different between groups. IMPLICATIONS:Treatment of L10/V80 or L10/V160 combination therapy resulted in significantly greater BP lowering compared with L10 monotherapy. Moreover, the L20/V160 high dose combination had additional BP lowering effect compared with nonresponders with the L10/V160 combination. ClinicalTrials.gov: NCT01928628.
Safety and efficacy of fimasartan in Mexican patients with grade 1-2 essential hypertension.
Cardona-Muñoz Ernesto G,López-Alvarado Agustín,Conde-Carmona Ignacio,Sánchez-Mejorada Gerardo,Pascoe-González Sara,Banda-Elizondo Ramiro G,García-Castillo Armando,González-Gálvez Guillermo,Velasco-Sánchez Raúl G,Vidrio-Velázquez Maricela,Leiva-Pons José L,Villeda-Espinosa Efraín,Guerra-López Arturo,Esturau-Santalo Ramón M
Archivos de cardiologia de Mexico
OBJECTIVE:To evaluate efficacy and safety of 60mg and 120mg Fimasartan (FMS) alone or combined with 12.5mg hydrochlorothiazide (HCTZ) in a Mexican population. METHODS:A six month, treat-to-target, open study was conducted on subjects with grade 1-2 hypertension. The subjects were initially treated with 60mg FMS once daily. In week 8, those with Diastolic Blood Pressure (DBP) <90mmHg continued on the same FMS dose during the rest of the study, while those with DBP ≥90mmHg were randomised to either 120mg FMS or 60mg FMS + 12.5mg HCTZ once daily. In week 12, randomised subjects with DBP ≥90mmHg received 120mg FMS+12.5mg HCTZ, while those achieving target continued with their assigned treatment until the end of the study. RESULTS:FMS 60mg (n=272) decreased both DBP and Systolic Blood Pressure (SBP) by 11.3±8.9 (p<.0001) and 16.0±14.1 (p<.0001)mmHg, respectively, with 75.4% of subjects reaching the treatment target. Subjects assigned to FMS 120mg, FMS 60mg+HCTZ 12.5mg, or FMS 120mg+HCTZ 12.5mg once daily, showed significant reductions in DBP and SBP with their assigned treatment. At the end of the study, 237/272 subjects (87.1%) achieved a DBP<90mmHg and an SBP<140mmHg. The most frequently reported adverse reactions included headache (3.7%), dry mouth (1.1%), transient liver enzyme increase (1.1%), and dizziness (0.7%). CONCLUSION:Fimasartan is safe and effective in Mexican subjects with grade 1-2 essential hypertension.
[Efficacy comparison between 5 mg perindopril arginine salt and 4 mg perindopril tert-butylamine salt for patients with mild to moderate essential hypertension].
Qi Litong,Zhao Shuiping,Li Hui,Guo Ying,Xu Geng,Ge Junbo,Wu Shirao,Miao Peizhi,Jin Yan,Yang Jiefu,Wu Xiaoqing,Ma Changsheng,Xu Dingli,Luo Jun,Wang Bin,Li Guangping,Wang Fengzhi,Shen Farong,Shi Haiming,Huo Yong
Zhonghua xin xue guan bing za zhi
OBJECTIVE:To compare the efficacy and safety of 5 mg perindopril arginine salt and 4 mg perindopril tert-butylamine salt for patients with mild to moderate essential hypertension. METHODS:The study was designed as multicenter, randomized, double-blind, active controlled trial with two parallel groups enrolling 524 participants with mild to moderate essential hypertension. After 2-week run-in period, 186 patients were enrolled and randomly treated with 5 mg perindopril arginine salt and 183 patients were enrolled and randomly treated with 4 mg perindopril tert-butylamine salt. The random sequence was generated by the I.R.I.S., and a balance was made in each center. After double-blind treatment for 8 weeks, the dose could be doubled for patients with uncontrolled BP ((SBP) ≥ 140 mmHg (1 mmHg = 0.133 kPa) or diastolic blood pressure (DBP) ≥ 90 mmHg) and patients were treated for another 4 weeks. RESULTS:The sitting SBP was similarly decreased by (19.9 ± 17.2) mmHg in perindopril arginine group and (18.5 ± 14.7) mmHg (P = 0.000 5) in perindopril tert-butylamine group post 8 weeks treatment. Dose was doubled in 109 patients (59.9%) in perindopril arginine group and 116 patients (63.7%) in perindopril tert-butylamine group. At 12 weeks post therapy, the sitting SBP decreased by (19.8 ± 16.2) and (19.6 ± 16.3) mmHg respectively in the 2 groups. The decrease of sitting DBP was also similar in both groups (-12.0 ± 10.0) mmHg and (-11.0 ± 8.9) mmHg (P < 0.000 1), respectively. The control rate or response rate was also similar between the two groups (control rate over 8 weeks was 38.5% vs. 31.3%, 95% CI (-2.6-16.9), control rate over 12 weeks was 36.3% vs. 35.7%, 95% CI (-9.3-10.4), response rate over 8 weeks was 64.3% vs. 63.2%, 95% CI (-8.8-11.0), response rate over 12 weeks was 65.9% vs. 64.8%, 95% CI (-8.7-10.9)). Incidence of adverse events was low and similar in both therapy groups. CONCLUSIONS:The results show that perindopril arginine salt 5 mg is as efficient as perindopril tert-butylamine 4 mg on lowering BP for patients with mild to moderate essential hypertension. Both drugs have good safety profile and are well tolerated by patients in this cohort.
A Randomized, Double-blind, Multicenter, Phase III Study to Evaluate the Efficacy and Safety of Fimasartan/Amlodipine Combined Therapy Versus Fimasartan Monotherapy in Patients With Essential Hypertension Unresponsive to Fimasartan Monotherapy.
Kim Kwang-Il,Shin Mi-Seung,Ihm Sang-Hyun,Youn Ho-Joong,Sung Ki-Chul,Chae Shung Chull,Nam Chang-Wook,Seo Hong Seog,Park Seong-Mi,Rhee Moo-Yong,Kim Moo Hyun,Cha Kwang Soo,Kim Yong-Jin,Kim Jae-Joong,Chun Kook Jin,Yoo Byung-Su,Park Sungha,Shin Eun-Seok,Kim Dong-Soo,Il Kim Doo,Kim Kye Hun,Joo Seung-Jae,Jeong Jin-Ok,Shin Jinho,Kim Cheol Ho
PURPOSE:The goal of this study was to evaluate whether the blood pressure-lowering efficacy of fimasartan/amlodipine combination therapy was superior to that of fimasartan monotherapy after 8 weeks of treatment in patients with hypertension who had failed to respond adequately to fimasartan monotherapy. METHODS:This trial was a randomized, double-blind, multicenter, Phase III clinical study. Patients who failed to respond after 4 weeks of treatment with 60 mg daily of fimasartan (sitting systolic blood pressure [SiSBP]) ≥140 mm Hg) were randomized to receive either daily fimasartan 60 mg or fimasartan/amlodipine 60 mg/10 mg. The primary efficacy end point was the change in SiSBP from baseline to week 8. Secondary end points included the change in SiSBP from baseline to week 4, the changes in sitting diastolic blood pressure from baseline to weeks 4 and 8, and the response rate (SiSBP <140 mm Hg or decrease in SiSBP ≥20 mm Hg) or control rate (SiSBP <140 mm Hg) at week 8. Treatment-emergent adverse events were also assessed. FINDINGS:Of 143 patients randomized to treatment, 137 patients who had available efficacy data were analyzed. The mean age of patients was 59.1 (8.9) years, and 100 (73.0%) were male. Baseline SiSBP and sitting diastolic blood pressure were 150.6 (9.2) mm Hg and 91.7 (8.6) mm Hg, respectively. In the fimasartan/amlodipine combination group, a greater reduction in SiSBP from baseline to week 8 was observed compared with the fimasartan group (7.8 [13.3] mm Hg in the fimasartan group vs 20.5 [14.6] mm Hg in the fimasartan/amlodipine group; P < 0.0001). This reduction was observed after 4 weeks. The mean SiSBP changes from baseline to week 4 were 8.1 (15.8) mm Hg in the fimasartan group and 20.1 (14.7) mm Hg in the fimasartan/amlodipine group (P < 0.0001). At week 8, the response rate was significantly higher in the fimasartan/amlodipine (82.1%) group than in the fimasartan (32.9%) group (P < 0.0001). The control rate at week 8 was also higher in the fimasartan/amlodipine (79.1%) group than in the fimasartan (31.4%) group (P < 0.0001). Adverse drug reactions were observed in 9 patients (6.3%), with no significant differences between treatment groups. There were no serious adverse events associated with the study drugs. IMPLICATIONS:Fimasartan/amlodipine combination therapy exhibited superior efficacy in reducing blood pressure, with no increase in adverse drug reactions, compared with fimasartan monotherapy. ClinicalTrials.gov identifier: NCT02152306.
Efficacy and Tolerability of Combination Therapy Versus Monotherapy with Candesartan and/or Amlodipine for Dose Finding in Essential Hypertension: A Phase II Multicenter, Randomized, Double-blind Clinical Trial.
Sohn Il Suk,Kim Chong-Jin,Ahn Taehoon,Youn Ho-Joong,Jeon Hui-Kyung,Ihm Sang Hyun,Cho Eun Joo,Chung Woo-Baek,Chae Shung Chull,Kim Woo-Shik,Nam Chang-Wook,Park Seong-Mi,Choi Ji-Yong,Kim Young-Kwon,Hong Taek-Jong,Lee Hae-Young,Cho Jang-Hyun,Shin Eun-Seok,Yoon Jung-Han,Yang Tae-Hyun,Jeong Myung-Ho,Lee Jun-Hee,Park Joong-Il
PURPOSE:Intensive blood pressure (BP) lowering is important for the treatment of hypertension; however, it has been a challenge to achieve target BP in many patients. The purpose of this study was to explore the optimal dosage of a fixed-dose combination of candesartan cilexetil (CAN) and amlodipine besylate (AML), by examining the tolerability and efficacy of CAN/AML combination therapy compared with those of monotherapy with either drug in patients with essential hypertension. METHODS:This Phase II multicenter, randomized, double-blind clinical trial enrolled patients aged 19 years or older with essential hypertension, defined as a mean sitting diastolic BP (msDBP) between 95 and 115 mm Hg, and a mean sitting systolic BP (msSBP) of <200 mm Hg after a 2-week placebo run-in period. A total of 635 patients were screened, of whom 439 were randomized to receive treatment; 425 patients were included in the full analysis set (combination therapy, 212; monotherapy, 213). Participants were randomly assigned to receive 1 of 8 treatments: CAN (8 or 16 mg), AML (5 or 10 mg), CAN/AML (8 mg/5 mg, 8 mg/10 mg, 16 mg/5 mg, or 16 mg/10 mg), once daily for 8 weeks. FINDINGS:After 8 weeks of treatment, changes in msDBP were significantly greater in the groups receiving CAN/AML combination therapies compared with monotherapies at matched doses, with the exception of CAN 8 mg/AML 10 mg versus AML 10 mg. The response to treatment and the achievement of target BP (both msSBP and msDBP) at week 8 were significantly greater overall in the groups that received combination therapy versus monotherapy. All medications were relatively well tolerated in each group. IMPLICATIONS:Eight-week administration of CAN/AML (8 mg/5 mg, 16 mg/5 mg, and 16 mg/10 mg) resulted in a significantly greater BP reduction than that with CAN or AML monotherapy, and was determined to be well tolerated. ClinicalTrials.gov identifier: NCT02944734.
Antihypertensive drug classes have different effects on short-term blood pressure variability in essential hypertension.
Levi-Marpillat Natacha,Macquin-Mavier Isabelle,Tropeano Anne-Isabelle,Parati Gianfranco,Maison Patrick
Hypertension research : official journal of the Japanese Society of Hypertension
Increased blood pressure variability (BPV) contributes to end-organ damage, cardiovascular events and mortality associated with hypertension. In a cohort of 2780 hypertensive patients treated by either calcium channel blockers (CCBs), diuretics, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) or β-blockers alone or in combination, we compared indices of short-term BPV according to the different treatments. Short-term BPV was calculated as the standard deviation (s.d.) of 24 h, daytime or nighttime systolic blood pressure and diastolic blood pressure (SBP and DBP). Short-term BPV was compared between patients treated with a given antihypertensive class of interest (alone or in combination) and those not treated with this class, after controlling for ambulatory average blood pressure, heart rate, age, gender, propensity scores and carotid-femoral pulse wave velocity. Patients treated with CCBs (n=1247) or diuretics (n=1486) alone, or in addition to other drugs had significant lower s.d. of 24-h SBP compared with those not treated with these classes (mean differences in s.d. -0.50±0.50 mm Hg, P=0.001 and -0.17±0.15 mm Hg, P=0.05, respectively). There was no significant difference regarding treatment with or without ARBs, ACEIs and β-blockers. The combinations of CCBs with diuretics or ARBs on top of other treatments resulted in a lower 24-h SBP variability (mean differences in s.d. -0.43±0.17 mm Hg, P=0.02 and -0.44±0.19 mm Hg, P=0.005 vs. other combination uses, respectively). Antihypertensive drug classes have differential effects on short-term BPV with a greater reduction in patients treated with CCBs and diuretics. The combinations of CCBs with diuretics may be the most efficient treatments in lowering BPV.
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.
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.
Effects of four different antihypertensive drugs on plasma metabolomic profiles in patients with essential hypertension.
Hiltunen Timo P,Rimpelä Jenni M,Mohney Robert P,Stirdivant Steven M,Kontula Kimmo K
OBJECTIVE:In order to search for metabolic biomarkers of antihypertensive drug responsiveness, we measured >600 biochemicals in plasma samples of subjects participating in the GENRES Study. Hypertensive men received in a double-blind rotational fashion amlodipine, bisoprolol, hydrochlorothiazide and losartan, each as a monotherapy for one month, with intervening one-month placebo cycles. METHODS:Metabolomic analysis was carried out using ultra high performance liquid chromatography-tandem mass spectrometry. Full metabolomic signatures (the drug cycles and the mean of the 3 placebo cycles) became available in 38 to 42 patients for each drug. Blood pressure was monitored by 24-h recordings. RESULTS:Amlodipine (P values down to 0.002), bisoprolol (P values down to 2 x 10-5) and losartan (P values down to 2 x 10-4) consistently decreased the circulating levels of long-chain acylcarnitines. Bisoprolol tended to decrease (P values down to 0.002) the levels of several medium- and long-chain fatty acids. Hydrochlorothiazide administration was associated with an increase of plasma uric acid level (P = 5 x 10-4) and urea cycle metabolites. Decreases of both systolic (P = 0.06) and diastolic (P = 0.04) blood pressure after amlodipine administration tended to associate with a decrease of plasma hexadecanedioate, a dicarboxylic fatty acid recently linked to blood pressure regulation. CONCLUSIONS:Although this systematic metabolomics study failed to identify circulating metabolites convincingly predicting favorable antihypertensive response to four different drug classes, it provided accumulating evidence linking fatty acid metabolism to human hypertension.