Dual Antiplatelet Therapy and the Severity Risk of Lower Intestinal Bleeding.
Carlin Neal,Asslo Fady,Sison Raymund,Shaaban Hamid,Baddoura Walid,Manji Faiza,Depasquale Joseph
Journal of emergencies, trauma, and shock
BACKGROUND:Dual antiplatelet (Plt) therapy with aspirin and clopidogrel is recommended for up to 1 year following acute coronary syndrome. Many of these cardiac patients are also on anithrombotic therapy like warfarin. Lower gastrointestinal bleeding (LGIB) is the main adverse event of this treatment. AIMS:The main purpose of this study was to analyze the relationship of dual anti-Plt therapy and the risk of LGIB. METHODS:Patients' electronic charts were reviewed to include a total of 19 variables, which included age, sex, ethnicity, daily use aspirin of any dose, daily use of clopidogrel, use of nonsteroidal anti-inflammatory drugs (NSAIDs) at least twice in the last week prior to admission and the daily use of anticoagulants (warfarin, heparin), and were obtained from history and physical examination reports, lab transcripts and procedural reports. SETTINGS/DESIGN:A retrospective cohort study of the records of 3436 patients admitted to our hospital from January 1, 2009, to December 31, 2011, was evaluated. All the patients included were admitted through the emergency department with complaints of or relating to LGIB. The primary outcome studied was severe LGIB as defined by the requirement of at least two units of packed red blood cells and/or a decrease in the hematocrit of 20% or more or recurrent bleeding after 24 h of clinical stability with additional transfusions required. Other outcomes included surgical intervention. STATISTICAL METHODS/ANALYSIS:Univariate analysis using -test on continuous variables and Chi-square test on categorical variables were done before carrying out logistic regression analysis. Logistic regression analyses were conducted to measures of association between the variables and LGIB. Logistic regression analysis was not carried for surgical intervention and death because none of the variables was significant from univariate tests. RESULTS:A total of 511 patients were found to have true LGIB. Among these subjects, 61 were shown to be on dual or multiple antithrombotic therapies. Further exploration revealed that while the use of multiple blood thinning agents may, in fact, pose a significant risk to overall LGIB, it did not significantly increase the risk for severe bleeding as outlined above. CONCLUSION:The use of multiple blood thinning agents does not significantly increase the risk for severe LGIB.
10.4103/JETS.JETS_110_15
Risk analysis of new oral anticoagulants for gastrointestinal bleeding and intracranial hemorrhage in atrial fibrillation patients: a systematic review and network meta-analysis.
Xu Wei-Wei,Hu Shen-Jiang,Wu Tao
Journal of Zhejiang University. Science. B
BACKGROUND:Antithrombotic therapy using new oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) has been generally shown to have a favorable risk-benefit profile. Since there has been dispute about the risks of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH), we sought to conduct a systematic review and network meta-analysis using Bayesian inference to analyze the risks of GIB and ICH in AF patients taking NOACs. METHODS:We analyzed data from 20 randomized controlled trials of 91 671 AF patients receiving anticoagulants, antiplatelet drugs, or placebo. Bayesian network meta-analysis of two different evidence networks was performed using a binomial likelihood model, based on a network in which different agents (and doses) were treated as separate nodes. Odds ratios (ORs) and 95% confidence intervals (CIs) were modeled using Markov chain Monte Carlo methods. RESULTS:Indirect comparisons with the Bayesian model confirmed that aspirin+clopidogrel significantly increased the risk of GIB in AF patients compared to the placebo (OR 0.33, 95% CI 0.01-0.92). Warfarin was identified as greatly increasing the risk of ICH compared to edoxaban 30 mg (OR 3.42, 95% CI 1.22-7.24) and dabigatran 110 mg (OR 3.56, 95% CI 1.10-8.45). We further ranked the NOACs for the lowest risk of GIB (apixaban 5 mg) and ICH (apixaban 5 mg, dabigatran 110 mg, and edoxaban 30 mg). CONCLUSIONS:Bayesian network meta-analysis of treatment of non-valvular AF patients with anticoagulants suggested that NOACs do not increase risks of GIB and/or ICH, compared to each other.
10.1631/jzus.B1600143
Gastrointestinal bleeding risk with rivaroxaban vs aspirin in atrial fibrillation: A multinational study.
Fanning Laura,Wong Ian C K,Li Xue,Chan Esther W,Mongkhon Pajaree,Man Kenneth K C,Wei Li,Leung Wai K,Darzins Peteris,Bell J Simon,Ilomaki Jenni,Lau Wallis C Y
Pharmacoepidemiology and drug safety
PURPOSE:Comparative gastrointestinal bleeding (GIB) risk between rivaroxaban and low-dose aspirin is unknown in patients with atrial fibrillation (AF). This study investigated GIB risk with rivaroxaban vs aspirin among two separate AF cohorts in Hong Kong and the United Kingdom, using a common protocol approach. METHODS:This was a population-based cohort study using separate data from the Clinical Data Analysis and Reporting System (CDARS) of the Hong Kong Hospital Authority (2010-2018) and The Health Improvement Network (THIN) database in the United Kingdom (2011-2017). Patients with AF newly prescribed aspirin or rivaroxaban were included. Cox proportional hazards regression was used to compare GIB risks for rivaroxaban vs aspirin, accounting for confounders using propensity score fine stratification approach. RESULTS:In CDARS, 29 213 patients were included; n = 1052 (rivaroxaban), n = 28 161 (aspirin). Crude GIB event rates per 100 patient-years in CDARS were 3.0 (aspirin) and 2.6 (rivaroxaban). No difference in GIB risk was observed between rivaroxaban and aspirin overall (HR = 1.04, 95%CI = 0.76-1.42), and in dose-stratified analyses (HR = 1.21, 95%CI = 0.84-1.74 [20 mg/day]; HR = 0.80, 95%CI = 0.44-1.45 [≤15 mg/day]). In THIN, 11 549 patients were included, n = 3496 (rivaroxaban) and n = 8053 (aspirin). Crude GIB event rates were 1.3 (aspirin) and 2.4 (rivaroxaban) per 100 patient-years. No difference in GIB risk was observed between rivaroxaban and aspirin overall (HR = 1.40, 95%CI = 1.00-1.98) and low-dose rivaroxaban (≤15 mg/day) (HR = 1.00, 95%CI = 0.56-1.30), but increased GIB risk was observed for rivaroxaban 20 mg/day vs aspirin (HR = 1.57, 95%CI = 1.08-2.29). CONCLUSION:In patients with AF, GIB risk was comparable between aspirin and rivaroxaban ≤15 mg/day. GIB risk for rivaroxaban 20 mg/day vs aspirin remains uncertain and warrants further investigation.
10.1002/pds.5130
Reduced risk of gastrointestinal bleeding associated with proton pump inhibitor therapy in patients treated with dual antiplatelet therapy after myocardial infarction.
Sehested Thomas S G,Carlson Nicholas,Hansen Peter W,Gerds Thomas A,Charlot Mette G,Torp-Pedersen Christian,Køber Lars,Gislason Gunnar H,Hlatky Mark A,Fosbøl Emil L
European heart journal
AIMS:Guidelines differ in their recommendations on therapy to prevent gastrointestinal bleeding for patients treated with dual antiplatelet treatment (DAPT). We sought to investigate the effectiveness of proton pump inhibitors (PPIs) to prevent upper gastrointestinal (UGI) bleeding in patients using DAPT following myocardial infarction (MI) in relation to current European Society of Cardiology guidelines recommendations. METHODS AND RESULTS:We linked Danish nationwide registries to identify patients taking DAPT 7 days following hospital discharge for an acute MI, and excluded individuals on anticoagulation therapy. We used multiple Cox regression modelling, to compute average risk of UGI bleeding in relation to PPI use. The associated treatment efficacy was compared based on guideline risk assessment. We studied 46 301 patients on DAPT after MI. Only 35% of patients at higher risk of UGI bleeding received recommended treatment with a PPI based on the guideline criteria. The 1--year risk of UGI bleeding was 1.0% [95% confidence interval (CI) 0.9-1.1%] and 1.7% (CI 1.5-2.0%) for high-risk patients. Overall PPI compared with no therapy, was associated with a risk ratio for UGI bleeding of 0.62 (CI 0.48-0.77) corresponding to an absolute risk difference of 0.44% (CI 0.39-0.48%). Proton pump inhibitor therapy was associated with a similar absolute risk difference [0.47% (CI 0.43-0.51%)] for high-risk patients. CONCLUSION:Proton pump inhibitor therapy is used less than suggested by guidelines in patients treated with DAPT following MI and was generally associated with reduced risk of UGI bleeding. Considering the overall low risk of bleeding, more focus should be on identifying patients benefiting the most from PPI therapy.
10.1093/eurheartj/ehz104
Risk Analysis of Colorectal Post-Polypectomy Bleeding Due to Antithrombotic Agent.
Kishida Yoshihiro,Hotta Kinichi,Imai Kenichiro,Ito Sayo,Yoshida Masao,Kawata Noboru,Tanaka Masaki,Kakushima Naomi,Takizawa Kohei,Ishiwatari Hirotoshi,Matsubayashi Hiroyuki,Ono Hiroyuki
Digestion
BACKGROUND/AIMS:Post-polypectomy bleeding (PPB) is a major complication of colorectal polypectomy, and antithrombotics is one of the major risk factors of PPB. The purpose of this study was to investigate PPB risks with regard to the combinations of antithrombotic agents used. METHODS:We retrospectively reviewed cases involving colonoscopic polyp resection between September 2002 and December 2014. The risk of PPB was assessed according to patient and lesion factors, including antithrombotic use. Antithrombotics were discontinued before polypectomy. RESULTS:A total of 6,382 colonoscopies with 12,876 polypectomies were analyzed. PPB occurred in 55 patients (0.9%) and 63 lesions (0.5%). Among patients treated with antithrombotics, heparin bridging (HB) therapy was an independent risk factor of PPB (per patient, 20%, OR 33.1, p < 0.001; per lesion, 9.1%, OR 17.3, p < 0.001) compared to those without antithrombotics (per patient 0.7%; per lesion 0.4%). Among patients without HB, the combination of anticoagulant + antiplatelet agents was significantly associated with PPB (per patient, 5%, OR 7.73, p = 0.007; per lesion, 2.4%, OR 6.31, p = 0.003). CONCLUSION:HB therapy is a major risk factor for PPB. Among patients without HB, anticoagulant + antiplatelet therapy was a significant risk factor for PPB.
10.1159/000490791
The risk of upper gastrointestinal bleeding associated with concomitant proton pump inhibitor administration during dual antiplatelet therapy with aspirin and prasugrel: a retrospective single-center study.
Journal of pharmaceutical health care and sciences
OBJECTIVE:Dual-antiplatelet therapy (DAPT) and proton pump inhibitor (PPI) are frequently prescribed after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) placement. However, studies that evaluate the optimal PPI when used as primary prevention in patients without a history of peptic ulcer disease or upper gastrointestinal bleeding (UGIB), particularly in the context of DAPT involving prasugrel, are lacking. This study aimed to assess the efficacy and safety of PPI use in preventing UGIB in this patient population. METHODS:This study included patients who underwent PCI with coronary stent placement for acute coronary syndrome or stable angina at our institution from January 2015 to December 2020. Eligible patients started DAPT with aspirin and prasugrel and concomitantly received PPI therapy (lansoprazole or esomeprazole), with a follow-up period of two years. The primary endpoint was UGIB incidence, diagnosed during follow-up, serving as an efficacy measure. Secondary endpoints included the assessment of major bleeding (as defined by the Thrombolysis in Myocardial Infarction major bleeding criteria) and clinically relevant non-major bleeding events. Safety outcomes focused on adverse event incidence attributable to PPI use. RESULTS:Among the 165 patients analyzed, 109 and 56 were included in the lansoprazole and esomeprazole groups, respectively, with cumulative incidence of UGIB at 96 weeks of 0.9% (1/109) and 3.6% (2/56). No significant differences in terms of major bleeding events or other bleeding outcomes were observed between the two groups. Adverse events related to PPI use were reported as diarrhea/soft stools in 7 (6%) cases and thrombocytopenia in 1 (1%) case in the lansoprazole group, whereas no such events were observed in the esomeprazole group. No clinically significant hematologic or biochemical abnormalities were reported. CONCLUSION:This study evaluated the efficacy and safety of PPIs in combination with DAPT, including prasugrel, following PCI, and suggests that lansoprazole and esomeprazole may offer comparable efficacy in preventing UGIB.
10.1186/s40780-024-00398-y
Systematic review with meta-analysis: the risk of major gastrointestinal bleeding with non-vitamin K antagonist oral anticoagulants.
Caldeira D,Barra M,Ferreira A,Rocha A,Augusto A,Pinto F J,Costa J,Ferreira J J
Alimentary pharmacology & therapeutics
BACKGROUND:Gastrointestinal (GI) bleeding is a common complication among anticoagulated patients. Non-vitamin K antagonist oral anticoagulants (NOACs) are associated with increased risk of GI (major and clinically relevant non-major) bleeding. However, more information is needed regarding severe events. AIM:To evaluate the risk of NOACs major GI bleeding. METHODS:We searched for phase III randomised clinical trials (RCT) evaluating NOACs (apixaban, dabigatran, edoxaban and rivaroxaban) and reporting major GI bleeding events, in MEDLINE, Cochrane Library, SciELO collection and Web of Science databases (July 2015). Meta-analysis was performed to estimate risk ratio (RR) and 95% confidence intervals (95% CIs). Heterogeneity was assessed with the I(2) test. RESULTS:A total of 23 studies were included. Among patients with atrial fibrillation, the risk of major GI bleeding was not different between NOACs and vitamin K antagonists (VKA) (RR 1.08, 95% CI 0.85-1.36, I(2) = 78%; 5 RCTs) or acetylsalicylic acid (RR 0.78, 95% CI 0.36-1.72; 1 RCT). Similar results were found for patients undergoing orthopaedic surgery and those with venous thromboembolism. NOACs were not found to increase the risk compared to low-molecular-weight heparin (LWMH) alone (RR 1.42, 95% CI 0.55-3.71, I(2) = 7%; 8 RCTs), the sequential treatment with LMWH-VKA (RR 0.77, 95% CI 0.49-1.21, I(2) = 43%; 7 RCTs) or placebo (RR 1.48, 95% CI 0.15-14.84, I(2) = 21%; 2 RCTs). CONCLUSION:Despite previous evidence supporting the association of non-vitamin K antagonist oral anticoagulants and overall GI bleeding, non-vitamin K antagonist oral anticoagulants are not associated with increased risk of major GI bleeding compared to other anticoagulant drugs (with known increased risk of these events).
10.1111/apt.13412
Risk of Major Gastrointestinal Bleeding With New vs Conventional Oral Anticoagulants: A Systematic Review and Meta-analysis.
Gu Zhi-Chun,Wei An-Hua,Zhang Chi,Wang Xin-Hua,Zhang Le,Shen Long,Li Zheng,Pan Mang-Mang,Liu Xiao-Yan,Pu Jun,Lin Hou-Wen
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
BACKGROUND & AIMS:There is controversy over whether use of non-vitamin K antagonist oral anticoagulants (NOACs) associates with increased risk of major gastrointestinal bleeding (GIB) compared with conventional therapies (such as vitamin K antagonists or anti-platelet agents). We performed a systematic review and meta-analysis of data from randomized controlled trials and high-quality real-world studies. METHODS:We performed a systematic search of the MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov Website databases (through Oct 12, 2018) for randomized controlled trials and high-quality real-world studies that reported major GIB events in patients given NOACs or conventional therapy. Relative risks (RRs) for randomized controlled trials and adjusted hazard ratios (aHRs) for real-world studies were calculated separately using random-effects models. RESULTS:We analyzed data from 43 randomized controlled trials (183,752 patients) and 41 real-world studies (1,879,428 patients). The pooled major rates of GIB for patients on NOACs (1.19%) vs conventional treatment (0.92%) did not differ significantly (RR from randomized controlled trials, 1.09; 95% CI, 0.91-1.31 and aHR from real-world studies, 1.02; 95% CI, 0.94-1.10; P=.52). Rivaroxaban, but not other NOACs, was associated with an increased risk for major GIB (RR from randomized controlled trials, 1.39; 95% CI, 1.17-1.65 and aHR from real-world studies, 1.14; 95% CI, 1.04-1.23; P = .06). Analyses of subgroups, such as patients with different indications, dosage, or follow-up time, did not significantly affect results. Meta-regression analysis failed to detect any potential confounding to impact the primacy outcome. CONCLUSIONS:In a systematic review and meta-analysis of data from randomized controlled trials and real-world studies, we confirmed that there is no significant difference in risk of major GIB between patients receiving NOACs vs conventional treatment. Rivaroxaban users had a 39% increase in risk for major GIB.
10.1016/j.cgh.2019.05.056
Risk of Gastrointestinal Bleeding in Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants: A Systematic Review and Meta-analysis.
Miller Corey S,Dorreen Alastair,Martel Myriam,Huynh Thao,Barkun Alan N
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
BACKGROUND & AIMS:Non-vitamin K antagonist oral anticoagulants (NOACs) are convenient and effective in the prevention and treatment of venous thromboembolism and the prevention of stroke in patients with atrial fibrillation. However, these drugs have been associated with an increased risk of gastrointestinal (GI) bleeding. We conducted a systematic review and meta-analysis to determine the risk of GI bleeding in patients receiving these drugs. METHODS:We searched the EMBASE, Medline, Cochrane, and ISI Web of knowledge databases through January 2016 for randomized trials that compared NOACs with conventional anticoagulants for approved indications. We conducted a meta-analysis, reporting odds ratios (ORs) with 95% confidence intervals (CIs). The primary outcome was major GI bleeding. Secondary outcomes included clinically relevant nonmajor bleeding and upper and lower GI bleeding. We performed a priori subgroup analyses by individual drug. RESULTS:Our analysis included a total of 43 randomized trials, comprising 166,289 patients. There was no difference between NOACs and conventional anticoagulants in the risk of major bleeding (1.5% vs 1.3%, respectively; OR, 0.98; 95% CI, 0.80-1.21), clinically relevant nonmajor bleeding (0.6% vs 0.6%, respectively; OR, 0.93; 95% CI, 0.64-1.36), upper GI bleeding (1.5% vs 1.6%, respectively; OR, 0.96; 95% CI, 0.77-1.20), or lower GI bleeding (1.0% vs 1.0%, respectively; OR, 0.88; 95% CI, 0.67-1.15). Dabigatran (2.0% vs 1.4%, respectively; OR, 1.27; 95% CI, 1.04-1.55) and rivaroxaban (1.7% vs 1.3%, respectively; OR, 1.40; 95% CI, 1.15-1.70) were associated with increased odds of major GI bleeding compared with conventional anticoagulation, whereas no difference was found for apixaban (0.6% vs 0.7%, respectively; OR, 0.81; 95% CI, 0.64-1.02) or edoxaban (1.9% vs 1.6%, respectively; OR, 0.93; 95% CI, 0.78-1.11). These subgroup findings were not observed in other sensitivity analyses. CONCLUSIONS:In a systematic review and meta-analysis, we found risk of major GI bleeding to be similar between NOACs and conventional anticoagulation. Dabigatran and rivaroxaban, however, may be associated with increased odds of major GI bleeding. Further high-quality studies are needed to characterize GI bleeding risk among NOACs.
10.1016/j.cgh.2017.04.031
Risk factors and management of gastrointestinal bleeding in patients with or without antiplatelet and anticoagulation therapy: a multicenter real-world prospective study.
BMC gastroenterology
BACKGROUND:Antiplatelet and anticoagulation drugs complicate acute gastrointestinal bleeding (GIB) patients. Limited data about the risk factors and patient management has been presented. This study explored the association between previous antiplatelet or anticoagulant drug usage and clinical outcomes in GIB patients to improve awareness further and optimize treatment. METHODS:We conducted a multicenter, non-interventional, real-world prospective study in 106 hospitals in 23 provinces in China. GIB patients confirmed in the emergency department were included and were grouped according to previous drug histories. Univariate analysis, multivariate logistic regression, and multivariate stratification models were performed separately to investigate the associations. RESULTS:A total of 2299 patients (57.23 ± 17.21 years old, 68.3% male) were included, of whom 20.1% and 2.9% received antiplatelet and anticoagulation therapy, respectively. The all-cause 28-day mortality rates in patients without antiplatelet or anticoagulants, patients undergoing antiplatelet treatment, and patients with anticoagulation therapy were 2.8%, 4.6%, and 10.5%, respectively. After adjusting for confounding factors, both antiplatelet [odd ratio (OR), 2.92; 95% confidence interval (CI), 1.48-5.76; p = 0.002] and anticoagulation therapy (OR, 8.87; 95% CI, 3.02-26.02; p < 0.001) were associated with higher 28-day mortality. In the subgroup analysis, blood transfusion, especially red blood cell transfusion, in patients undergoing antiplatelet and anticoagulation therapy was associated with a decreased death risk. CONCLUSION:We confirmed an association between concurrent antiplatelet or anticoagulation therapy in GIB patients and elevated 28-day mortality. Blood transfusions could improve poor outcomes in such patients.
10.1186/s12876-024-03238-3
Real-World Bleeding Risk of Anticoagulant and Nonsteroidal Anti-inflammatory Drugs Combotherapy versus Anticoagulant Monotherapy.
Gut and liver
Background/Aims:The incidence of acute gastrointestinal bleeding (GIB) increases with the utilization of anticoagulant and nonsteroidal anti-inflammatory drugs (NSAIDs). This study aimed to compare the risk of GIB between anticoagulant and NSAIDs combotherapy and anticoagulant monotherapy in real-world practice. Methods:We investigated the relative risk of GIB in individuals newly prescribed anticoagulant and NSAIDs combination therapy and that in individuals newly prescribed anticoagulant monotherapy at three hospitals using "common data model." Cox proportional hazard models and Kaplan-Meier estimation were employed for risk comparison after propensity score matching. Results:A comprehensive analysis of 2,951 matched pairs showed that patients who received anticoagulant and NSAIDs combousers exhibited a significantly higher risk of GIB than those who received anticoagulant monousers (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.30 to 2.12; p<0.001). The risk of GIB associated with anticoagulant and NSAIDs combination therapy was also significantly higher than that associated with anticoagulant monotherapy in patients aged >65 years (HR, 1.53; 95% CI, 1.15 to 2.03; p=0.003) and >75 years (HR, 1.89; 95% CI, 1.23 to 2.90; p=0.003). We also found that the risk of GIB was significantly higher in the patients who received anticoagulant and NSAIDs combousers than that in patients who received anticoagulant monousers in both male (p=0.016) and female cohorts (p=0.010). Conclusions:The risk of GIB is significantly higher in patients who receive anticoagulant and NSAIDs combotherapy than that in patients who receive anticoagulant monotherapy. In addition, the risk of GIB associated with anticoagulant and NSAIDs combotherapy was much higher in individuals aged >75 years. Therefore, physicians should be more aware of pay more attention to the risk of GIB when they prescribe anticoagulant and NSAIDs.
10.5009/gnl230541
Real-World Risk of Gastrointestinal Bleeding for Direct Oral Anticoagulants and Warfarin Users: A Distributed Network Analysis Using a Common Data Model.
Gut and liver
Background/Aims:Early studies on direct oral anticoagulants (DOACs) reported a higher risk of gastrointestinal bleeding (GIB) compared with warfarin; however, recent studies have reported a reduced risk. Therefore, this study was designed to evaluate the risk of GIB in users of DOAC and warfarin. Methods:Using a common data model, we investigated the comparative risk of GIB in subjects from eight hospitals who were newly prescribed DOACs or warfarin. We excluded subjects who had a prior history of GIB or had been prescribed both medications. After propensity score matching, we analyzed 3,347 matched pairs of new DOAC and new warfarin users. Results:The risk of GIB in new DOAC users was comparable to that in new warfarin users (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.65 to 1.40; p=0.808). New DOAC users had a similar risk of GIB to new warfarin users among older patients >65 years (HR, 1.00; 95% CI, 0.69 to 1.52; p=0.997) and in older patients >75 years (HR, 1.21; 95% CI, 0.68 to 2.10; p=0.509). In addition, the risk of GIB was not significantly different between two groups according to sex. We also found that the risk of GIB in DOAC users was 26% lower in edoxaban or apixaban subgroups compared to rivaroxaban or dabigatran subgroups (HR, 0.74; 95% CI, 0.69 to 1.00; p=0.049). Conclusions:In real-world practice, the risk of GIB in new DOAC users is comparable to that in new warfarin users. In DOAC users, the risk of GIB was lower in edoxaban or apixaban subgroups than rivaroxaban or dabigatran subgroups.
10.5009/gnl230406
Re-bleeding and all-cause mortality risk in non-variceal upper gastrointestinal bleeding: focusing on patients receiving oral anticoagulant therapy.
Annals of medicine
OBJECTIVE:Non-variceal upper gastrointestinal bleeding (NVUGIB) in patients receiving oral anticoagulants (OACs) may be fatal; however, little is known about re-bleeding and all-cause mortality after successful hemostasis. We investigated the clinical characteristics and risk factors for re-bleeding and death after successful hemostasis. METHODS:Patients receiving OACs and diagnosed with NVUGIB between 2007 and 2021 were enrolled. All NVUGIB incidents were confirmed if definite bleeding in the upper gastrointestinal tract was detected esophagogastroduodenoscopy. RESULTS:A total of 132 patients receiving OACs were diagnosed with NVUGIB. Males were the majority (72, 54.5%), and bleeding was detected mostly in the stomach (99, 75%) and was most often due to peptic ulcers (PU) (88, 66.7%). After successful hemostasis of index NVUGIB, 40 patients (30.3%) experienced re-bleeding. Among them, 15 (37.5%) died, and among those, 3 (2.3%) were related to re-bleeding. Multivariate analysis revealed that duodenal bleeding (odds ratio [OR]: 3.305; 95% confidence interval [CI]: 1.152-9.479, = 0.026) and Charlson comorbidity index score (CCI) (OR: 1.22; 95% CI: 1.052-1.419, = 0.009) were significant risk factors for re-bleeding. Index albumin levels (OR: 0.134; 95% CI: 0.035-0.506, = 0.003), previous PU or upper gastrointestinal bleeding (UGIB) history (OR: 4.626; 95% CI: 1.375-15.567, = 0.013), and CCI (OR: 1.293; 95% CI: 1.058-1.581, = 0.012) were related all-cause mortality. CONCLUSION:CCI and duodenal bleeding are risk factors for re-bleeding in patients with NVUGIB who were receiving OACs, while low index albumin levels and previous PU and UGIB history are associated with all-cause mortality.
10.1080/07853890.2023.2253822
Challenges of Anticoagulant Therapy in Atrial Fibrillation-Focus on Gastrointestinal Bleeding.
International journal of molecular sciences
The rising prevalence and the complexity of atrial fibrillation (AF) pose major clinical challenges. Stroke prevention is accompanied by non-negligible risks, making anticoagulant treatment an ongoing challenge for the clinician. Current guidelines recommend direct oral anticoagulants (DOACs) over warfarin for stroke prevention in most AF patients, mainly due to the ease of their use. However, assessing the bleeding risk in patients receiving oral anticoagulants remains-particularly in the case of DOACs-highly challenging. Using dose-adjusted warfarin increases threefold the risk of gastrointestinal bleeding (GIB). Although the overall bleeding risk appears to be lower, the use of DOACs has been associated with an increased risk of GIB compared to warfarin. Accurate bleeding (including GIB-specific) risk scores specific for DOACs remain to be developed. Until then, the assessment of bleeding risk factors remains the only available tool, although the extent to which each of these factors contributes to the risk of bleeding is unknown. In this paper, we aim to provide a comprehensive review of the bleeding risk associated with oral anticoagulant therapy in AF patients, with a highlight on the latest insights into GIB associated with oral anticoagulation; we emphasize questions that remain to be answered; and we identify hotspots for future research.
10.3390/ijms24086879
Gastrointestinal Bleeding During Direct Oral Anticoagulant Therapy in Patients With Nonvalvular Atrial Fibrillation and Risk of Polypharmacy.
Journal of clinical pharmacology
Although concomitant medications have been raised as a factor affecting hemorrhage during direct oral anticoagulant (DOAC) therapy, details remain unelucidated. This study was conducted to clarify the relationship between concomitant medications with possible pharmacokinetic interactions and number of concomitant medications, and bleeding and embolism in patients with nonvalvular atrial fibrillation on DOACs. The subjects were 1010 patients prescribed DOACs from a single-center at the Teikyo University Hospital between April 2011 and June 2018. This study was an exploratory analysis and investigated their course between the first prescription and December 2018, including the presence or absence of clinically relevant bleeding, gastrointestinal bleeding, and major cardiovascular and cerebrovascular events. Impacts of medications were evaluated by the general linear model with inverse probability-weighted propensity score. The observation period was 2272 patient-years. The rate of bleeding was 4.7%/year, gastrointestinal bleeding was 2.8%/year, and major cardiovascular and cerebrovascular events were 2.0%/year. Taking 10 or more oral medications concurrently was a significant risk for gastrointestinal bleeding (hazard ratio, 2.046 [95%CI, 1.188-3.526]; P = .010). Nonsteroidal anti-inflammatory drugs were the only significant risk for gastrointestinal bleeding. Clinicians should be aware of gastrointestinal bleeding when using DOACs with patients taking more than 10 medications and/or nonsteroidal anti-inflammatory drugs.
10.1002/jcph.2106
Risk of gastrointestinal bleeding during anticoagulant treatment.
Lanas-Gimeno Aitor,Lanas Angel
Expert opinion on drug safety
INTRODUCTION:Gastrointestinal bleeding (GIB) is a major problem in patients on oral anticoagulation therapy. This issue has become even more pressing since the introduction of direct oral anticoagulants (DOACs) in 2009. Areas covered: Here we review current evidence related to GIB associated with oral anticoagulants, focusing on randomized controlled trials, meta-analyses, and post-marketing observational studies. Dabigatran 150 mg twice daily and rivaroxaban 20 mg once daily increase the risk of GIB compared to warfarin. The risk increase with edoxaban is dose-dependent, while apixaban shows apparently, no increased risk. We summarize what is known about GIB risk factors for individual anticoagulants, the location of GIB in patients taking these compounds, and prevention strategies that lower the risk of GIB. Expert opinion: Recently there has been an important shift in the clinical presentation of GIB. Specifically, upper GIB has decreased with the decreased incidence of peptic ulcers due to the broad use of proton pump inhibitors and the decreased prevalence of H. pylori infections. In contrast, the incidence of lower GIB has increased, due in part to colonic diverticular bleeding and angiodysplasia in the elderly. In this population, the addition of oral anticoagulation therapy, especially DOACs, seems to increase the risk of lower GIB.
10.1080/14740338.2017.1325870
Association of Oral Anticoagulants and Proton Pump Inhibitor Cotherapy With Hospitalization for Upper Gastrointestinal Tract Bleeding.
Ray Wayne A,Chung Cecilia P,Murray Katherine T,Smalley Walter E,Daugherty James R,Dupont William D,Stein C Michael
JAMA
Importance:Anticoagulant choice and proton pump inhibitor (PPI) cotherapy could affect the risk of upper gastrointestinal tract bleeding, a frequent and potentially serious complication of oral anticoagulant treatment. Objectives:To compare the incidence of hospitalization for upper gastrointestinal tract bleeding in patients using individual anticoagulants with and without PPI cotherapy, and to determine variation according to underlying gastrointestinal bleeding risk. Design, Setting, and Participants:Retrospective cohort study in Medicare beneficiaries between January 1, 2011, and September 30, 2015. Exposures:Apixaban, dabigatran, rivaroxaban, or warfarin with or without PPI cotherapy. Main Outcomes and Measures:Hospitalizations for upper gastrointestinal tract bleeding: adjusted incidence and risk difference (RD) per 10 000 person-years of anticoagulant treatment, incidence rate ratios (IRRs). Results:There were 1 643 123 patients with 1 713 183 new episodes of oral anticoagulant treatment included in the cohort (mean [SD] age, 76.4 [2.4] years, 651 427 person-years of follow-up [56.1%] were for women, and the indication was atrial fibrillation for 870 330 person-years [74.9%]). During 754 389 treatment person-years without PPI cotherapy, the adjusted incidence of hospitalization for upper gastrointestinal tract bleeding (n = 7119) was 115 per 10 000 person-years (95% CI, 112-118). The incidence for rivaroxaban (n = 1278) was 144 per 10 000 person-years (95% CI, 136-152), which was significantly greater than the incidence of hospitalizations for apixaban (n = 279; 73 per 10 000 person-years; IRR, 1.97 [95% CI, 1.73-2.25]; RD, 70.9 [95% CI, 59.1-82.7]), dabigatran (n = 629; 120 per 10 000 person-years; IRR, 1.19 [95% CI, 1.08-1.32]; RD, 23.4 [95% CI, 10.6-36.2]), and warfarin (n = 4933; 113 per 10 000 person-years; IRR, 1.27 [95% CI, 1.19-1.35]; RD, 30.4 [95% CI, 20.3-40.6]). The incidence for apixaban was significantly lower than that for dabigatran (IRR, 0.61 [95% CI, 0.52-0.70]; RD, -47.5 [95% CI,-60.6 to -34.3]) and warfarin (IRR, 0.64 [95% CI, 0.57-0.73]; RD, -40.5 [95% CI, -50.0 to -31.0]). When anticoagulant treatment with PPI cotherapy (264 447 person-years; 76 per 10 000 person-years) was compared with treatment without PPI cotherapy, risk of upper gastrointestinal tract bleeding hospitalizations (n = 2245) was lower overall (IRR, 0.66 [95% CI, 0.62-0.69]) and for apixaban (IRR, 0.66 [95% CI, 0.52-0.85]; RD, -24 [95% CI, -38 to -11]), dabigatran (IRR, 0.49 [95% CI, 0.41-0.59]; RD, -61.1 [95% CI, -74.8 to -47.4]), rivaroxaban (IRR, 0.75 [95% CI, 0.68-0.84]; RD, -35.5 [95% CI, -48.6 to -22.4]), and warfarin (IRR, 0.65 [95% CI, 0.62-0.69]; RD, -39.3 [95% CI, -44.5 to -34.2]). Conclusions and Relevance:Among patients initiating oral anticoagulant treatment, incidence of hospitalization for upper gastrointestinal tract bleeding was the highest in patients prescribed rivaroxaban, and the lowest for patients prescribed apixaban. For each anticoagulant, the incidence of hospitalization for upper gastrointestinal tract bleeding was lower among patients who were receiving PPI cotherapy. These findings may inform assessment of risks and benefits when choosing anticoagulant agents.
10.1001/jama.2018.17242
Major gastrointestinal bleeding in patients receiving anticoagulant therapy for venous thromboembolism.
Thrombosis research
INTRODUCTION:The gastrointestinal (GI) tract is a frequent site of bleeding in patients receiving anticoagulant therapy for venous thromboembolism (VTE). At-risk patients have not been consistently identified yet. METHODS:We used the RIETE registry to assess the clinical characteristics of patients developing major GI bleeding during the course of anticoagulation. Then, we built a predictive score based on multivariable analysis, aiming to identify patients at increased risk for major GI bleeding. RESULTS:We included 87,431 patients with acute VTE. During the course of anticoagulation, 778 (0.89%) suffered major GI bleeding, 815 (0.93%) non-major GI bleeding and 1462 (1.67%) had major bleeding outside the GI tract. During the first 30 days after major GI bleeding, 7.6% of patients re-bled, 3.9% had VTE recurrences and 33% died. On multivariable analysis, male sex, age ≥70 years, initial VTE presentation as pulmonary embolism, active cancer, prior VTE, recent major bleeding in the GI tract, esophageal varicosities, anemia, abnormal prothrombin time, renal insufficiency and use of corticosteroids were associated to an increased risk for major GI bleeding. Using the predictive score, 39,591 patients (45%) were at low risk; 36,602 (42%) at intermediate-risk; 9315 (11%) at high-risk; and 1923 (2.2%) at very high risk. Their rates of major GI bleeding were: 0.21%, 0.96%, 2.41% and 6.08%, respectively. The c-statistics was 0.771 (95%CI. 0.755-0.786). CONCLUSIONS:We have developed a score which has the potential to identify patients at increased risk for GI bleeding, but needs to be externally validated."
10.1016/j.thromres.2022.04.005
Reduction of Upper Gastrointestinal Bleeding Risk With Proton Pump Inhibitor Therapy in Asian Patients With Atrial Fibrillation Receiving Direct Oral Anticoagulant: A Nationwide Population-based Cohort Study.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
BACKGROUND & AIMS:In patients with atrial fibrillation (AF) receiving direct oral anticoagulant (DOAC), upper gastrointestinal bleeding (UGIB) is a serious complication. There are limited data on the benefit of preventive proton pump inhibitor (PPI) use to reduce the risk of UGIB in DOAC users. METHODS:We included patients with AF receiving DOAC from 2015 to 2020 based on the Korean Health Insurance Review and Assessment database. The propensity score (PS) weighting method was used to compare patients with PPI use and those without PPI use. The primary outcome was hospitalization for UGIB. Weighted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were evaluated using the Cox proportional hazards regression model. RESULTS:A total of 165,624 patients were included (mean age: 72.2 ± 10.8 years; mean CHADS-VASc score: 4.3 ± 1.8; mean HAS-BLED score: 3.3 ± 1.2). Among them, 99,868 and 65,756 were in the non-PPI group and PPI group, respectively. During a median follow-up of 1.5 years, the PPI group was associated with lower risks of hospitalization for UGIB and UGIB requiring red blood cell transfusion than non-PPI group (weighted HR, 0.825; 95% CI, 0.761-0.894 and 0.798; 95% CI, 0.717-0.887, respectively, both P < .001). The benefits of PPI on the risk of hospitalization for UGIB were greater in those with older age (≥75 years), higher HAS-BLED score (≥3), prior GIB history, and concomitant use of antiplatelet agent (all P-for-interaction < .1). Low-dose PPI was consistently associated with a lower risk of significant UGIB by 43.6-49.3% (P < .001). CONCLUSIONS:In this large Asian cohort of patients with AF on DOAC, PPI co-therapy is beneficial for reducing the risk of hospitalization for UGIB, particularly in high-risk patients.
10.1016/j.cgh.2023.12.022
Review Article: Gastrointestinal Bleeding Risk with Direct Oral Anticoagulants.
Cardiovascular drugs and therapy
PURPOSE:Although direct oral anticoagulants (DOACs) are associated with an overall favourable safety profile, the risk of gastrointestinal bleeding with DOACs compared with vitamin K antagonists (VKAs) remains controversial. Accordingly, we aimed to provide a focused overview of the risk of gastrointestinal bleeding associated with dabigatran, rivaroxaban, apixaban and edoxaban and its management. METHODS:We reviewed published studies reporting on DOACs with gastrointestinal bleeding as an outcome, including randomised controlled trials (RCTs), retrospective database studies and large-scale prospective cohort studies. RESULTS:Cumulative evidence confirms no notable difference in major gastrointestinal bleeding risk between DOACs and VKAs. Moreover, gastrointestinal bleeding in DOAC-treated patients seems less severe and requires less intensive management. The main cause of upper gastrointestinal bleeding in DOAC-treated patients appears to be gastroduodenal ulcers, whereas lower gastrointestinal bleedings are mainly due to diverticula followed by angiodysplasia and haemorrhoids. The lack of head-to-head RCTs with DOACs precludes drawing conclusions on the DOAC with the lowest gastrointestinal bleeding risk. Prescribing physicians should be aware of risk factors for DOAC-related gastrointestinal bleeding (e.g. age > 65, heavy alcohol use, uncontrolled hypertension, hepatic or renal dysfunction, active cancer, anaemia) and adopt preventive measures accordingly. Management of DOAC-associated major gastrointestinal bleeding involves temporary discontinuation of the DOAC, investigation of the bleeding source and treatment of bleeding with fluid resuscitation combined with transfusion and endoscopic haemostasis. CONCLUSION:DOACs as a class do not increase the risk of major gastrointestinal bleeding compared to VKAs, which supports their continued use for different anticoagulant indications.
10.1007/s10557-021-07211-0
Risk of gastrointestinal bleeding with direct oral anticoagulants: a systematic review and network meta-analysis.
Burr Nick,Lummis Katie,Sood Ruchit,Kane John Samuel,Corp Aaron,Subramanian Venkataraman
The lancet. Gastroenterology & hepatology
BACKGROUND:Direct oral anticoagulants are increasingly used for a wide range of indications. However, data are conflicting about the risk of major gastrointestinal bleeding with these drugs. We compared the risk of gastrointestinal bleeding with direct oral anticoagulants, warfarin, and low-molecular-weight heparin. METHODS:For this systematic review and meta-analysis, we searched MEDLINE and Embase from database inception to April 1, 2016, for prospective and retrospective studies that reported the risk of gastrointestinal bleeding with use of a direct oral anticoagulant compared with warfarin or low-molecular-weight heparin for all indications. We also searched the Cochrane Library for systematic reviews and assessment evaluations, the National Health Service (UK) Economic Evaluation Database, and ISI Web of Science for conference abstracts and proceedings (up to April 1, 2016). The primary outcome was the incidence of major gastrointestinal bleeding, with all gastrointestinal bleeding as a secondary outcome. We did a Bayesian network meta-analysis to produce incidence rate ratios (IRRs) with 95% credible intervals (CrIs). FINDINGS:We identified 38 eligible articles, of which 31 were included in the primary analysis, including 287 692 patients exposed to 230 090 years of anticoagulant drugs. The risk of major gastrointestinal bleeding with direct oral anticoagulants did not differ from that with warfarin or low-molecular-weight heparin (factor Xa vs warfarin IRR 0·78 [95% CrI 0·47-1·08]; warfarin vs dabigatran 0·88 [0·59-1·36]; factor Xa vs low-molecular-weight heparin 1·02 [0·42-2·70]; and low-molecular-weight heparin vs dabigatran 0·67 [0·20-1·82]). In the secondary analysis, factor Xa inhibitors were associated with a reduced risk of all severities of gastrointestinal bleeding compared with warfarin (0·25 [0.07-0.76]) or dabigatran (0.24 [0.07-0.77]). INTERPRETATION:Our findings show no increase in risk of major gastrointestinal bleeding with direct oral anticoagulants compared with warfarin or low-molecular-weight heparin. These findings support the continued use of direct oral anticoagulants. FUNDING:Leeds Teaching Hospitals Charitable Foundation.
10.1016/S2468-1253(16)30162-5