Risk of Recurrent Bleeding Events in Nonvalvular Atrial Fibrillation Treated with Vitamin K Antagonists: A Clinical Practice Research Datalink Study.
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SUBMITTER: Alikhan R
PROVIDER: S-EPMC6777986 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AIMS:We compared the 1-year safety and effectiveness of dabigatran 110 mg (D110) or 150 mg (D150) twice daily to vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation. METHODS:New user cohort study of patients dispensed D110 or D150 vs. VKA in 2013 for nonvalvular atrial fibrillation, followed 1 year in the French Système National des Données de Santé (66 million persons). D110 and D150 users were matched 1:1 with VKA users on sex, age, date of first drug dispensing and high-dimensional propensity score. Hazard ratios [HR (95% confidence intervals)] for stroke and systemic embolism (SSE), major bleeding (MB) and death were computed using Cox proportional hazards or Fine and Gray models during exposure. RESULTS:In 14?442 matched D110 and VKA patients, mean age 79, 49% male, 91% with CHA2 DS2 -VASc ?2 and 8% with HAS-BLED score >3, incidence rates of SSE were 1.9% and 2.6% person-years [HR 0.69 (0.56-0.84)], MB 1.8% and 2.9% [0.62 (0.51-0.76)], death 7.2% and 8.6% [0.84 (0.76-0.94)]. In 8389 matched D150 and VKA patients, mean age 67, 67% male, 65% with CHA2 DS2 -VASC ?2; < 5% HAS-BLED >3, incidence rates were for SSE 1.4% and 1.9% [0.76 (0.56-1.04)], MB 0.6% and 1.9% [0.30 (0.20-0.46)], death 1.6% and 3.6% [0.46 (0.35-0.59)]. Numbers needed to treat to observe one fewer death were 78 for D110, 88 for D150. CONCLUSION:In real life D110 and D150 were at least as effective, and safer than VKA.
| S-EPMC6339969 | biostudies-literature
Project description:There are limited data on the clinical presentations and management of dabigatran-associated major bleeding outside the clinical trial setting. The aim of this study is to describe clinical characteristics, interventions, and outcomes in patients with dabigatran-associated major bleeding who present to the emergency department (ED).We performed a retrospective observational chart review study of dabigatran-treated patients with nonvalvular atrial fibrillation who presented with acute major bleeding to the ED. We searched electronic medical record databases cross-referencing medication lists and hemorrhage International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes. We studied the resulting charts to yield confirmed nonvalvular atrial fibrillation in patients with an index event of major bleeding and at least 1 dose of dabigatran in the 5 preceding days.The electronic search yielded 284 cases, and we assessed 93 as ineligible, leaving 191 in the final cohort. Of these, 118 patients (62%) had gastrointestinal hemorrhage; 36 (19%) had intracranial hemorrhage, 8 (4%) of which were nontraumatic cases and 28 (15%) traumatic. Thirty-six (19%) of the index events were in "other" locations and 1 (0.5%) "unknown." There were 12 deaths (6%): 8 from patients presenting with gastrointestinal bleeding events, 2 from intracranial hemorrhage (both nontraumatic), and 2 from other. Although RBC and plasma transfusions were common, only 11 patients (6%) received purified coagulation factors.Despite rare use of reversal strategies, mortality was low and outcomes were favorable, similar to reported outcomes from clinical trials, in this sample of patients with major bleeding while receiving dabigatran.
| S-EPMC5568766 | biostudies-literature
Project description:ImportanceMany patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastrointestinal (GI) bleeding due to conditions including older age; stage III to V chronic kidney disease (CKD); HAS-BLED (hypertension, kidney or liver disease, stroke history, prior bleeding, unstable international normalized ratio, age >65, drug or alcohol use) score of 3 or greater; corticosteroid, antiplatelet or nonsteroidal anti-inflammatory drug (NSAID) use; or GI conditions.ObjectiveTo compare the risk of stroke and/or systemic embolism (SE) and major bleeding (MB) among patients with NVAF and high risk of GI bleeding who received non-vitamin K antagonist oral anticoagulants (NOACs) vs those who received warfarin.Design, setting, and participantsThis retrospective cohort study included patients with NVAF who were 75 years and older; had stage III to V CKD; had an HAS-BLED score of 3 or greater; used corticosteroids, antiplatelets, or NSAIDs; or had GI conditions. Data were collected from the Centers for Medicare & Medicaid Services and 4 commercial insurance databases between January 1, 2012, and September 30, 2015. Data analysis was conducted from January 2012 to September 2015.ExposuresNew prescription for apixaban, dabigatran, rivaroxaban, or warfarin between January 1, 2013, and September 30, 2015 (identification period).Main outcomes and measuresSix propensity score-matched cohorts were created to compare between study drugs. For the primary objective, Cox models were used to estimate stroke and/or SE and MB hazard ratios (HRs).ResultsA total of 381 054 patients (187 489 [49.2%] women) with NVAF and at least 1 high-risk GI bleeding factor were identified (HAS-BLED score ≥3: 284 527 [74.7%]; aged ≥75 years: 252 835 [66.4%]; corticosteroid, antiplatelet, or NSAID therapy: 107 675 [28.3%]; prior GI bleeding conditions: 74 818 [19.6%]; and stage III-V CKD: 56 892 [14.9%]). All NOACs were associated with a lower risk of stroke and/or SE vs warfarin (apixaban: HR, 0.60; 95% CI, 0.52-0.68; dabigatran: HR, 0.75; 95% CI, 0.64-0.88; rivaroxaban: HR, 0.79; 95% CI, 0.73-0.86). Compared with warfarin, apixaban and dabigatran were associated with a lower risk of MB (apixaban: HR, 0.59; 95% CI, 0.56-0.63; dabigatran: HR, 0.78; 95% CI, 0.70-0.86), while rivaroxaban was associated with a higher risk (HR, 1.11; 95% CI, 1.05-1.16).Conclusions and relevanceIn this study of patients with NVAF and high risk of GI bleed, NOACs were associated with lower rates of stroke and/or SE, but NOACs had varying risks of MB compared with warfarin. These results may help inform treatment options in this patient population.
| S-EPMC8369361 | biostudies-literature
Project description:BackgroundIt remains uncertain whether patients with atrial fibrillation (AF) requiring long-term oral anticoagulation (OAC) and with stable coronary artery disease (CAD) should receive antiplatelet therapy (APT) in addition to OAC.HypothesisAPT in addition to OAC would be more effective than OAC alone in preventing ischaemic events in such patients.MethodsIn the international REduction of Atherothrombosis for Continued Health (REACH) Registry including 68 236 outpatients with or at risk for atherothrombosis, we identified 2347 patients with stable CAD and AF receiving vitamin K antagonists (VKA). Using propensity score matching, patients treated with VKA (n = 1481) were compared with those receiving VKA + APT at inclusion (n = 866). The primary outcome was major adverse cardiovascular events (MACE) at 4 years (cardiovascular death, myocardial infarction, or stroke). Secondary outcomes were all-cause death and bleeding leading to hospitalization and transfusion.ResultsPatients receiving VKA only were older (74 vs 72 years, P < 0.01), had less diabetes (37% vs 42%, P = 0.02), and less frequent history of percutaneous coronary intervention (28.7% vs 43.9%, P < 0.01). The mean CHA2 DS2 -VaSc score was 4.9 in the VKA group vs 4.7 in the VKA + APT group (P < 0.01). After propensity score matching, the rate of MACE was similar between groups: hazard ratio = 1.01 (0.77-1.33) (P = 0.94), whereas bleeding tended to be more frequent in the VKA + APT group: odds ratio = 1.87 (0.99-3.50) (P = 0.051).ConclusionsIn this observational analysis, the use of APT in addition to OAC in patients with stable CAD and AF was not associated with lower risk of ischemic events but possibly with higher bleeding rates. Randomized trials are necessary to determine the optimal long-term antithrombotic strategy.
| S-EPMC6490437 | biostudies-literature
Project description:BackgroundDirect oral anticoagulants (DOACs) have widely replaced warfarin for stroke prevention in nonvalvular atrial fibrillation. Our objective was to compare the safety and effectiveness of DOACs (dabigatran, rivaroxaban, apixaban) versus warfarin for stroke prevention in nonvalvular atrial fibrillation in the Canadian setting.MethodsWe conducted a population-based observational multicentre cohort study with propensity score matching and subsequent meta-analysis. We used health care databases from 7 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec and Nova Scotia). Patients with nonvalvular atrial fibrillation who initiated anticoagulation therapy in 2009-2017 were matched to an equal number who initiated warfarin. The primary outcome was the pooled hazard ratio (HR) for ischemic stroke or systemic embolization. Secondary outcomes included pooled HRs for major bleeding; a composite outcome of stroke, systemic embolization, major bleeding and all-cause mortality; and myocardial infarction. We modelled HRs using proportional hazard Cox regression with inverse probability of censoring weights, and estimated pooled HRs with random-effect meta-analyses.ResultsWe included 128 273 patients who initiated anticoagulation with a DOAC (40 503 dabigatran, 49 498 rivaroxaban and 38 272 apixaban) and 128 273 patients who initiated anticoagulation with warfarin. The pooled HR for ischemic stroke or systemic embolization comparing DOACs to warfarin was 1.02 (95% confidence interval [CI] 0.87 to 1.19). Direct oral anticoagulants were associated with lower rates of major bleeding (pooled HR 0.81, 95% CI 0.69 to 0.97), the composite outcome (pooled HR 0.81, 95% CI 0.74 to 0.89) and all-cause mortality (pooled HR 0.81, 95% CI 0.78 to 0.85).InterpretationIn this real-world study, DOACs were associated with similar risks of ischemic stroke or systemic embolization, and lower risks of bleeding and total mortality compared to warfarin. These findings support the use of DOACs for anticoagulation in nonvalvular atrial fibrillation.Trial registrationClinicalTrials.gov, no. NCT03596502.
| S-EPMC7759115 | biostudies-literature
Project description:AimsClinical trials have shown that anticoagulation with vitamin K antagonists (VKAs), e.g. warfarin, decreases the risk of stroke in patients with atrial fibrillation (AF); however, increased bleeding risk is one of the safety concerns. The primary objective was to conduct a systematic review of the published literature, assessing the risk of major bleeding and mortality in patients with AF treated with VKAs.Methods and resultsOnline searches of MEDLINE, EMBASE, BIOSIS, and the Cochrane Library were performed to a pre-specified protocol from 1960 to March 2012 for randomized controlled trials (RCTs) and from January 1990 to March 2012 for observational studies. A total of 47 studies (16 RCTs and 31 observational studies) were included. Cumulative follow-up was 61,563 patient-years for RCTs and 484 241 patient-years for observational studies. The overall median incidence of major bleeding was 2.1 per 100 patient-years (range, 0.9-3.4 per 100 patient-years) for RCTs and 2.0 per 100 patient-years (range, 0.2-7.6 per 100 patient-years) for observational studies. With study year as a proxy for changing management patterns, some evidence of bleeding rates and/or their reporting increasing over time was noted. Mortality rates from observational studies were inadequately reported to allow comparison with those from RCT data.ConclusionThe median rate of major bleeding in observational studies and RCTs is similar. The larger heterogeneity in bleeding rates observed in a real-life setting could reflect a high variability in standard of care of patients on VKAs and/or methodological differences between observational studies and/or variability in data sources.
| S-EPMC3663334 | biostudies-literature
Project description:BackgroundReal-world effectiveness and safety of antithrombotics in nonvalvular atrial fibrillation (NVAF) patients in Singapore has not been thoroughly studied.HypothesisUsers of various antithrombotics experience a significantly different risk of stroke and major bleed compared with warfarin users.MethodsThis multicenter retrospective cohort study included patients age ≥ 21 years newly diagnosed with NVAF between July 2012 and September 2015. Using electronic medical records, data on patients' demographics, antithrombotics prescribed, and CHA2 DS2 -VASc and HAS-BLED risk factors were collected. Patients were followed for 1 year from diagnosis for the primary effectiveness and safety endpoints of incident stroke or systemic embolism and major bleed, respectively. The secondary safety endpoint was overall bleed. Hazard ratios (HR) were determined from Cox regression.ResultsOf 743 patients included, 224 were on warfarin, 156 on direct oral anticoagulants (DOACs), 277 on single antiplatelet therapy (SAPT), 28 on dual antiplatelet therapy (DAPT), and 58 on no therapy. Mean age (±SD) was 68.7 ± 13.0 years. Compared with warfarin users, SAPT (adjusted [adj.] HR: 3.70, 95% confidence interval [CI]: 1.21-11.3) and DAPT users (adj. HR: 10.1, 95% CI: 1.51-67.2) were more likely to develop thromboembolic outcomes. Also, DOAC users (adj. HR: 0.304, 95% CI: 0.158-0.585), SAPT users (adj. HR: 0.142, 95% CI: 0.0680-0.295), and DAPT users (adj. HR: 0.112, 95% CI: 0.0146-0.857) were less likely to experience any bleed compared with warfarin users.ConclusionsSAPT and DAPT are less effective than warfarin in NVAF patients. DOACs may be considered in view of lower risk of overall bleed.
| S-EPMC6490354 | biostudies-literature
Project description:ImportanceDirect oral anticoagulants (DOACs) are purported to have fewer drug-drug interactions than warfarin. However, potential interactions with coprescribed medications are still a safety concern. Verapamil hydrochloride and diltiazem hydrochloride are combined P-glycoprotein (P-gp) and CYP3A4 inhibitors and may be associated with increases in the risk of bleeding with DOACs.ObjectiveTo evaluate the risk of bleeding with DOACs and verapamil or diltiazem using an active comparator design.Design, setting, and participantsA comparative effectiveness active comparator cohort study was conducted using US population-based data (2010-2015) analyzed between January 1 and July 15, 2019. Data were obtained on 48 442 patients with nonvalvular atrial fibrillation who had received an index prescription of dabigatran, rivaroxaban, or apixaban between October 19, 2010, through June 30, 2015, with final follow-up on October 1, 2015. Analysis was restricted to individuals with no history of kidney disease who were receiving standard doses of the DOACs.ExposuresPatients with initial prescriptions of DOACs who were receiving verapamil or diltiazem were compared with those receiving amlodipine or metoprolol.Main outcomes and measuresOverall and gastrointestinal major, moderate, and minor bleeding using primary or secondary diagnoses. Hazard ratios and 95% CIs were estimated using inverse probability of treatment weights in Cox proportional hazards regression models.ResultsOf the 48 442 patients reviewed, analysis was conducted on 1764 patients receiving DOACs with verapamil or diltiazem compared with 3105 receiving amlodipine and 1793 patients receiving DOACs with verapamil or diltiazem compared with 3224 receiving metoprolol. Depending on the comparison, approximately 60% of the cohort were younger than 65 years and male, which differed by treatment group. Rivaroxaban and apixaban were not associated with increased rates of bleeding for patients receiving verapamil or diltiazem compared with those receiving amlodipine or metoprolol. Among patients receiving dabigatran etexilate, the overall bleeding rate was 52% higher (hazard ratio, 1.52; 95% CI, 1.05-2.20) with verapamil or diltiazem vs amlodipine and 43% higher (hazard ratio, 1.43; 95% CI, 1.02-2.00) vs metoprolol. Bleeding rates for dabigatran with verapamil or diltiazem were higher overall for other bleeding types (244.9 vs 158.4 per 1000 person-years; adjusted hazard ratios of overall GI bleeding: 2.16; 95% CI, 1.30-3.60; minor bleeding: 1.56; 95% CI, 1.07-2.27; and minor GI bleeding: 2.16; 95% CI, 1.29-3.63). Sensitivity analyses showed consistent results for dabigatran when used with verapamil and diltiazem, with magnitudes ranging from 50% to 100% increased hazard rates and no significant results for apixaban or rivaroxaban.Conclusions and relevanceCurrent US prescribing information only recommends prescribing changes with dabigatran and P-gp inhibitors with lower kidney function. This study found increased bleeding risk associated with dabigatran when used concomitantly with the P-gp inhibitors verapamil and diltiazem in individuals with normal kidney function. Clinicians and patients may need to consider these drug-drug interactions when choosing oral anticoagulation.
| S-EPMC7182798 | biostudies-literature
Project description:BackgroundBlood pressure (BP) fluctuates significantly in patients with atrial fibrillation (AF); office BP measurements seem insufficient to assess AF patient risk accurately. We hypothesized that home BP could better predict the risk of stroke/systemic embolic events (SEE) and major bleeding in patients with AF than office BP.MethodsIn this prespecified subcohort study of the ANAFIE (All Nippon AF in the Elderly) Registry, we evaluated the impact of home BP on the risk of stroke/SEE, major bleeding, intracranial hemorrhage, all-cause death, and net cardiovascular outcome (a composite of stroke/SEE and major bleeding). At enrollment, home BP was measured twice in the morning and evening for 7 days.ResultsIn total, 4933 elderly patients (aged ≥75 years) with nonvalvular AF participated. Incidences of net cardiovascular outcome, stroke/SEE, major bleeding, and intracranial hemorrhage increased significantly with increasing home systolic BP (H-SBP). Compared with H-SBP <125 mm Hg, ≥145 mm Hg was associated with increased risk of these events. The association between H-SBP and the events was observed only in patients with ≥20 H-SBP measurements.ConclusionsIn elderly patients with nonvalvular AF, high H-SBP (≥145 mm Hg) was a significant predictor of stroke/SEE, major bleeding, and intracranial hemorrhage risk. Strict BP control guided by the increasing number of home BP measurements may provide an accurate clinical outcome risk assessment.RegistrationURL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000024006.
| S-EPMC9640260 | biostudies-literature
Project description:Non-vitamin K oral anticoagulants (NOACs) are commonly prescribed with other medications that share metabolic pathways that may increase major bleeding risk.To assess the association between use of NOACs with and without concurrent medications and risk of major bleeding in patients with nonvalvular atrial fibrillation.Retrospective cohort study using data from the Taiwan National Health Insurance database and including 91?330 patients with nonvalvular atrial fibrillation who received at least 1 NOAC prescription of dabigatran, rivaroxaban, or apixaban from January 1, 2012, through December 31, 2016, with final follow-up on December 31, 2016.NOAC with or without concurrent use of atorvastatin; digoxin; verapamil; diltiazem; amiodarone; fluconazole; ketoconazole, itraconazole, voriconazole, or posaconazole; cyclosporine; erythromycin or clarithromycin; dronedarone; rifampin; or phenytoin.Major bleeding, defined as hospitalization or emergency department visit with a primary diagnosis of intracranial hemorrhage or gastrointestinal, urogenital, or other bleeding. Adjusted incidence rate differences between person-quarters (exposure time for each person during each quarter of the calendar year) of NOAC with or without concurrent medications were estimated using Poisson regression and inverse probability of treatment weighting using the propensity score.Among 91?330 patients with nonvalvular atrial fibrillation (mean age, 74.7 years [SD, 10.8]; men, 55.8%; NOAC exposure: dabigatran, 45?347 patients; rivaroxaban, 54?006 patients; and apixaban, 12?886 patients), 4770 major bleeding events occurred during 447?037 person-quarters with NOAC prescriptions. The most common medications co-prescribed with NOACs over all person-quarters were atorvastatin (27.6%), diltiazem (22.7%), digoxin (22.5%), and amiodarone (21.1%). Concurrent use of amiodarone, fluconazole, rifampin, and phenytoin with NOACs had a significant increase in adjusted incidence rates per 1000 person-years of major bleeding than NOACs alone: 38.09 for NOAC use alone vs 52.04 for amiodarone (difference, 13.94 [99% CI, 9.76-18.13]); 102.77 for NOAC use alone vs 241.92 for fluconazole (difference, 138.46 [99% CI, 80.96-195.97]); 65.66 for NOAC use alone vs 103.14 for rifampin (difference, 36.90 [99% CI, 1.59-72.22); and 56.07 for NOAC use alone vs 108.52 for phenytoin (difference, 52.31 [99% CI, 32.18-72.44]; P?<?.01 for all comparisons). Compared with NOAC use alone, the adjusted incidence rate for major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin and was not significantly different for concurrent use of verapamil; diltiazem; cyclosporine; ketoconazole, itraconazole, voriconazole, or posaconazole; and dronedarone.Among patients taking NOACs for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin compared with the use of NOACs alone, was associated with increased risk of major bleeding. Physicians prescribing NOAC medications should consider the potential risks associated with concomitant use of other drugs.
| S-EPMC5818856 | biostudies-other