Safety and effectiveness of rivaroxaban for prevention of stroke in patients with nonvalvular atrial fibrillation: analysis of routine clinical data from four countries

Background: Rivaroxaban is a novel oral anticoagulant approved in the US in 2011 for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). Information on risks and benefits among rivaroxaban users in real-world populations is limited. Methods: We used data from the US MarketScan Commercial and Medicare Supplemental databases between 2010 and 2013. We selected patients with a history of NVAF and initiating rivaroxaban or warfarin. Rivaroxaban users were matched with up to 5 warfarin users by age, sex, database enrollment date and drug initiation date. Ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding outcomes were defined by ICD-9-CM codes in an inpatient claim after drug initiation date. Cox proportional hazards models were used to assess the association between rivaroxaban vs. warfarin use and outcomes adjusting for age, sex, and CHA2DS2-VASc score. Separate models were used to compare a) new rivaroxaban users with new warfarin users, and b) switchers from warfarin to rivaroxaban to continuous warfarin users. Results: Our analysis included 34,998 rivaroxaban users matched to 102,480 warfarin users with NVAF (39% female, mean age 71), in which 487 ischemic strokes, 179 ICB, 647 MI, and 1353 GI bleeds were identified during a mean follow-up of 9 months. Associations of rivaroxaban vs warfarin were similar in new users and switchers; therefore we pooled both analyses. Rivaroxaban users had lower rates of ICB (hazard ratio (HR) (95% confidence interval (CI)) = 0.72 (0.46, 1.12))) and ischemic stroke (HR (95% CI) = 0.88 (0.68, 1.13)), but higher rates of GI bleeding (HR (95% CI) = 1.15 (1.01, 1.33)) when compared to warfarin users (table). Conclusion: In this large population-based study of NVAF patients, rivaroxaban users had a non-significant lower risk of ICB and ischemic stroke than warfarin users, but a higher risk of GI bleeding. These real-world findings are comparable to results reported in published clinical trials.

BackgroundRivaroxaban is an oral anticoagulant approved in the US for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). We determined the effectiveness and associated risks of rivaroxaban versus other oral anticoagulants in a large real-world population.MethodsWe selected NVAF patients initiating oral anticoagulant use in 2010–2014 enrolled in MarketScan databases. Rivaroxaban users were matched with warfarin and dabigatran users by age, sex, enrolment date, anticoagulant initiation date, and high-dimensional propensity score. Study endpoints, including ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding, were identified from inpatient diagnostic codes. Multivariable Cox models were used to assess associations between type of anticoagulant and outcomes.ResultsThe analysis included 44,340 rivaroxaban users matched to 89,400 warfarin and 16,957 dabigatran users (38% female, mean age 70) with 12 months of mean follow-up. Anticoagulant-naïve rivaroxaban initiators, but not those switching from warfarin, had lower risk of ischemic stroke [hazard ratio (HR) (95% confidence interval (CI)): 0.75 (0.62, 0.91)] and ICB [HR (95%CI): 0.55, (0.39, 0.78)] than warfarin users. In contrast, anticoagulant-experienced rivaroxaban initiators had higher risk of GI bleeding than warfarin users [HR (95%CI): 1.55 (1.32, 1.83)]. Endpoint rates were similar when comparing anticoagulant-naïve rivaroxaban and dabigatran initiators, with the exception of higher GI bleeding risk in rivaroxaban users [HR (95%CI) 1.28 (1.06, 1.54)]. There were no significant differences in the risk of MI among the comparison groups.ConclusionIn this large real-world sample of NVAF patients, effectiveness and risks of rivaroxaban versus warfarin differed by prior anticoagulant status, while effectiveness of rivaroxaban versus dabigatran differed in GI bleeding risk.

BackgroundWarfarin is commonly used as a secondary prevention of stroke in patients with atrial fibrillation (AF). However, limitations have been observed even with the use of this medication. Recently, several newer direct oral anticoagulants (DOACs) have been approved for use by the food and drug administrations. Unfortunately, these newer drugs have seldom been compared directly with each other. Therefore, this study aimed to compare the bleeding events associated with rivaroxaban and dabigatran in patients treated for non-valvular AF.MethodsEMBASE, Medline (National Library of Medicine) and the Cochrane Central Registry of Controlled Trials were searched for studies comparing rivaroxaban with dabigatran using the terms ‘rivaroxaban, dabigatran and atrial fibrillation’. Primary endpoints were: any bleeding outcomes, intracranial bleeding and gastro-intestinal (GI) bleeding. Secondary outcomes included stroke/systemic embolism (SE)/transient ischemic attack (TIA), venous thromboembolism and mortality. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated. The pooled analyses were carried out with RevMan 5.3 software. All the authors had full access to the data and approved the manuscript as written.ResultsA total number of 4895 patients were included. This analysis showed that rivaroxaban was not associated with a significantly higher bleeding event when compared to dabigatran (OR: 1.28, 95% CI: 0.95–1.72; P = 0.11). GI bleeding was similarly manifested between these two DOACs (OR: 0.98, 95% CI: 0.43–2.25; P = 0.97). Even if intracranial bleeding was higher with the use of rivaroxaban, (OR: 2.18, 95% CI: 0.51–9.25; P = 0.29), the result was not statistically significant. Moreover, stroke/SE/TIA and venous thromboembolism were also not significantly different (OR: 0.81, 95% CI: 0.53–1.23; P = 0.32) and (OR: 2.06, 95% CI: 0.73–5.82; P = 0.17) respectively. However, even if mortality favored dabigatran (OR: 1.42, 95% CI: 0.99–2.06; P = 0.06), this result only approached statistical significance.ConclusionHead to head comparison showed that rivaroxaban was not associated with significantly higher bleeding events compared to dabigatran. Intracranial bleeding, GI bleeding, stroke/SE/TIA, venous thromboembolism and mortality were also not significantly different between these two DOACs. However, due to the limited number of patients analyzed, and which were mainly obtained from observational studies, this hypothesis might only be confirmed in future randomized trials. Furthermore, the CHADS2-VASC and HAS-BLED score which might play an important role in predicting bleeding risks should also not be ignored.

Introduction: The choice of anticoagulant for patients with non-valvular atrial fibrillation (AF) in the setting of active cancer has not been well studied given only a minority of patients with cancer included in clinical trials. Hypothesis: Cancer patients will have similar rates of stroke (CVA), gastrointestinal bleeding (GIB), and intracranial hemorrhage (ICH) when treated with direct oral anticoagulants (DOAC) compared to warfarin (VKA) for AF. Methods: A retrospective study was performed at MD Anderson Cancer Center on patients with cancer and AF being treated with VKA or DOAC. The outcomes assessed were overall mortality, CVA, GIB, or ICH and patients were censored at 5 years. 1:1 propensity score matching was conducted to select comparable patients receiving VKA versus DOAC. Multivariable Cox proportional hazards regression models were fitted for each outcome. Results: A total of 1133 patients were included in the dataset with mean age of 72 years, 42% women, and 74% received DOAC (57% received apixaban). At 5 year follow up, mortality occurred in 145, CVA in 59, GIB in 59, and ICH in 6 patients. The baseline risk scores were higher for those on VKA compared to DOAC (CHADSVASC 3.5±1.6 vs 3.3±1.7 p=0.04, HASBLED 2.0 ± 1.1 vs 1.8 ± 1.0 p<0.01). After propensity score matching 210 patients were included in each anticoagulant group. Survival analysis showed higher GIB free survival in the DOAC group however no difference was observed for composite GIB, CVA, or ICH (Figure). On multivariate analysis the risk of GIB was higher in the VKA group (HR 3.1, 95% CI 1.3-7.3); however, risk of mortality (HR 1.1, 95% CI 0.7-1.8), CVA (HR 0.9, 95% CI 0.4-1.8), ICH (HR 0.3, 95% CI 0.0-2.2), and composite of GIB, CVA, or ICH (HR 1.3, 95% CI 0.8-2.3) were not different comparing VKA to the DOAC propensity matched group. Conclusion: Patients with active cancer have higher risk of GIB but similar overall survival and risk for composite stroke and bleeding when treated with VKA compared to DOAC for AF.

Risk factors and comorbidities can complicate management of non-valvular atrial fibrillation. We describe and compare real-world safety and effectiveness of direct oral anticoagulants (DOACs; apixaban, rivaroxaban, dabigatran) and vitamin K antagonists (VKAs) in subgroups of patients with non-valvular atrial fibrillation at high risk for gastrointestinal (GI) bleeding, utilizing data from a national quasi-exhaustive French database. Anticoagulant-naïve adults with non-valvular atrial fibrillation with ≥1 gastrointestinal bleeding risk factor, initiating anticoagulant treatment January 2016-December 2019, and covered by the French national health data system were eligible. The following subgroups were evaluated: patients age ≥75 years, receiving concomitant medications, HAS-BLED score ≥3, and chronic kidney disease stage 3-4. Outcomes included major bleeding and stroke/systemic embolism. Patient characteristics were balanced using propensity score matching. A total of 314,184 patients were identified; characteristics were similar for propensity score-matched subgroups in VKA/DOAC and DOAC/DOAC comparisons. DOACs showed lower risk of major bleeding versus VKAs in all subgroups evaluated (p<0.0001 for all). Apixaban showed lower risk of major bleeding and gastrointestinal bleeding versus rivaroxaban in all subgroups (p≤0.05 for all) and versus dabigatran in elderly patients, patients with HAS-BLED score ≥3, and those receiving concomitant medications (p<0.05 for all). Stroke/systemic embolism risk was lower with apixaban versus rivaroxaban in elderly patients, those with HAS-BLED ≥3, and those receiving concomitant medications; risks were similar for other comparisons. DOACs were associated with improved safety and effectiveness when compared to VKAs among subgroups of non-valvular atrial fibrillation patients at high risk of gastrointestinal bleeding. Apixaban was associated with lower risks of major bleeding, gastrointestinal bleeding, and stroke/systemic embolism versus rivaroxaban as well as lower risk of major bleeding, gastrointestinal bleeding bleed and similar risk of stroke/systemic embolism versus dabigatran among several of these patient subgroups.

Introduction: Dronedarone (DR), a P-gp and CYP 3A4 inhibitor may increase exposure and the risk of bleeding when combined with direct oral anticoagulants (DOACs). Objective: To examine the association between concomitant use of DR and the DOACs, apixaban (A), dabigatran (D), and rivaroxaban (R), and risk of bleeding compared to DOAC monotherapy in patients with atrial fibrillation (AF). Methods: A retrospective cohort study using a U.S. claims database, Truven Health MarketScan identified new users of A, D, and R in patients with AF ≥18 years from Jan 1, 2007 to Sep 30, 2017. Bleeding was defined as hospitalization or emergency room visit with a primary diagnosis of gastrointestinal (GI) bleeding, intracranial hemorrhage (ICH), or bleeding at other sites. Risk of overall and by type of bleeding was examined in concomitant users of DOAC and DR compared to patients using DOAC alone after adjusting for covariates of interest and applying propensity score (PS) trimming via Cox proportional hazards modeling. Results: Among concomitant users of DR and A (1,932), D (3,117), and R (2,395), crude incidence rates of bleeding per 1,000 person-years were 17.2, 37.8, 61.8, respectively versus 26.8, 31.3, and 44.9 in users of A (51,420), D (42,312), and R (57,300) alone. Incidence rates stratified by PS showed higher bleeding incidence in concomitant users of DR with D or R, but not with A. No increased bleeding risk was associated with use of DR and A vs A alone [Adjusted Hazard ratio (aHR): 0.69 (95% CI: 0.40, 1.17), p=0.16]. A modestly increased risk of GI bleeding but not overall bleeding was associated with combined use of DR and D vs D alone [aHR bleeding: 1.18 (95% CI: 0.89, 1.56), p=0.26; aHR GI bleeding: 1.40 (95% CI: 1.01, 1.93); p=0.04]. An increased risk of overall bleeding, driven by GI bleeding, was associated with combined use of DR and R vs R alone [aHR bleeding:1.31 (95% CI: 1.01, 1.69); p=0.04; aHR GI bleeding:1.39 (95% CI: 0.98, 1.95); p=0.06]. There was no increase in the risk of ICH associated with combined use of DR and any DOAC. Conclusions: Concomitant treatment with DR and A showed no increased risk of bleeding, but DR increased the risk of GI bleeding when given with D or R, and of overall bleeding only with R. Concomitant treatment with DR and any DOAC did not increase ICH risk.

Background: Edoxaban and rivaroxaban for stroke prevention in non-valvular atrial fibrillation (NVAF) patients with CHADS 2 ≥2 have been evaluated in pivotal trials versus warfarin. This study assessed the cost-effectiveness of once-daily edoxaban (60 mg/30 mg dose-reduced) regimen versus rivaroxaban (20 mg/15 mg dose-reduced) for stroke prevention in patients with NVAF patients from a US health plan perspective. Methods: A Markov model simulated lifetime risk and treatment of stroke, systemic embolism, major bleeding, clinically relevant non-major bleeding, myocardial infarction, and death in NVAF patients treated with edoxaban or rivaroxaban. Efficacy and safety data were from a network meta-analysis using data from patients enrolled in ENGAGE AF-TIMI 48 and ROCKET-AF that were presented previously. 2015 wholesale acquisition cost (WAC) was used for edoxaban and rivaroxaban in the analysis. Healthcare cost and utility data were from published sources. Incremental cost-effectiveness ratios of &lt;$50,000, $50,000-$150,000, and &gt;$150,000 per quality-adjusted life year (QALY) gained were used as thresholds for highly cost-effective, cost-effective, and not cost-effective treatment option per guidance from the AHA/ACC statement on cost/value methodology in clinical practice guidelines and performance measures. Results: Edoxaban was dominant relative to rivaroxaban, such that it was associated with lower total healthcare cost and better effectiveness in terms of QALYs in the base case analysis (Table). Results were supported by probabilistic sensitivity analyses that showed edoxaban as either dominant or a highly cost-effective alternative (ICER&lt;$50,000) to rivaroxaban 88.4% of the time. Conclusions: These results showed that once-daily edoxaban (60mg/30mg dose-reduced) regimen is a highly cost-effective treatment relative to rivaroxaban (20mg/15mg dose-reduced) for stroke prevention in NVAF patients.

ImportanceIt remains unclear whether dabigatran etexilate mesylate is associated with higher risk of bleeding than warfarin sodium in real-world clinical practice.ObjectiveTo compare the risk of bleeding associated with dabigatran and warfarin using Medicare data.Design, Setting, and ParticipantsIn this retrospective cohort study, we used pharmacy and medical claims in 2010 to 2011 from a 5% random sample of Medicare beneficiaries. We identified participants as those newly diagnosed as having atrial fibrillation from October 1, 2010, through October 31, 2011, and who initiated dabigatran or warfarin treatment within 60 days of initial diagnosis. We followed up patients until discontinued use or switch of anticoagulants, death, or December 31, 2011.ExposuresDabigatran users (n = 1302) and warfarin users (n = 8102).Main Outcomes and MeasuresWe identified any bleeding events and categorized them as major and minor bleeding by anatomical site. Major bleeding events included intracranial hemorrhage, hemoperitoneum, and inpatient or emergency department stays for hematuria, gastrointestinal, or other hemorrhage. We used a propensity score weighting mechanism to balance patient characteristics between 2 groups and Cox proportional hazards regression models to evaluate the risk of bleeding. We further examined the risk of bleeding for 4 subgroups of high-risk patients: those 75 years or older, African Americans, those with chronic kidney disease, and those with more than 7 concomitant comorbidities.ResultsDabigatran was associated with a higher risk of bleeding relative to warfarin, with hazard ratios of 1.30 (95% CI, 1.20-1.41) for any bleeding event, 1.58 (95% CI, 1.36-1.83) for major bleeding, and 1.85 (95% CI, 1.64-2.07) for gastrointestinal bleeding. The risk of intracranial hemorrhage was higher among warfarin users, with a hazard ratio of 0.32 (95% CI, 0.20-0.50) for dabigatran compared with warfarin. Dabigatran was consistently associated with an increased risk of major bleeding and gastrointestinal hemorrhage for all subgroups analyzed. The risk of major bleeding among dabigatran users was especially high for African Americans and patients with chronic kidney disease.Conclusions and RelevanceDabigatran was associated with a higher incidence of major bleeding (regardless of the anatomical site), a higher risk of gastrointestinal bleeding, but a lower risk of intracranial hemorrhage. Thus, dabigatran should be prescribed with caution, especially among high-risk patients.

AimsWe aimed to evaluate bleeding risk in clinical practice in patients with atrial fibrillation (AF) being prescribed dabigatran, rivaroxaban, or apixaban compared with warfarin.MethodsUsing nationwide registries (Norwegian Patient Registry and Norwegian Prescription Database), we identified AF patients with a first prescription of oral anticoagulants between January 2013 and June 2015. Patients were followed until discontinuation or switching of oral anticoagulants, death, or end of follow-up. The primary endpoint was major or clinically relevant non-major (CRNM) bleeding.ResultsIn total 32 675 AF patients were identified (58% men, median age 74 years): 11 427 patients used warfarin, 7925 dabigatran, 6817 rivaroxaban, and 6506 apixaban. After a median follow-up of 173 days (25th, 75th percentile 84, 340), 2081 (6.37%) patients experienced a first major or CRNM bleeding. Using a Cox proportional hazard model adjusting for baseline characteristics, use of apixaban [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.61–0.80, P < 0.001] and dabigatran (HR 0.74, 95% CI 0.66–0.84, P < 0.001) were associated with a lower risk of major or CRNM bleeding compared with warfarin whereas use of rivaroxaban was not (HR: 1.05, 95% CI 0.94–1.17, P = 0.400). Use of dabigatran and rivaroxaban were associated with higher risk of gastrointestinal bleeding, whereas use of apixaban and dabigatran were associated with lower risk of intracranial bleeding, compared with warfarin.ConclusionIn this nationwide cohort study in AF patients, apixaban and dabigatran were associated with a lower risk of major or CRNM bleeding compared with warfarin. The risk of gastrointestinal bleeding was higher with rivaroxaban and dabigatran compared with warfarin.

Introduction: The utilization of direct oral anticoagulant (DOAC) agents for atrial fibrillation (AF) in individuals with end-stage renal disease (ESRD) has increased despite a lack of robust supportive data from randomized controlled trials. We planned to assess the outcomes associated with rivaroxaban versus warfarin in the ESRD population with AF. Methods: We utilized the TriNetX Global Collaborative Network, which includes 114 Healthcare organizations to perform a propensity-score matched retrospective cohort study. We used ICD-10 codes to identify individuals with ESRD and AF, over 18 years of age, excluding those with prosthetic valves and apixaban or edoxaban use. Data were collected from 2011 to 2024. We evaluated the incidence of ischemic stroke (I63), intracranial hemorrhage (I62.9), cardiac arrest (I46), mortality, gastrointestinal (GI) hemorrhage (K92.2), systemic embolism and thrombosis (I74.3, I74.2), and other cardiac arrythmias (I49). We performed propensity-score matching (PSM) on age, sex, race, BMI, hypertension, diabetes mellitus, tobacco use, heart failure, stroke, or acute myocardial infarction. Results: We identified 25,092 individuals in the warfarin group and 2,391 individuals in the rivaroxaban group. After PSM, 2,381 individuals remained in each group. The average age was 72.9, predominantly male (59.8%), with 62.9% white, 14.7% African American, and 6.5% Hispanic individuals. Compared to those treated with warfarin, individuals treated with rivaroxaban demonstrated a lower risk of a composite outcome (Infarct, intracranial hemorrhage, mortality) (RR 0.823, 95% CI 0.765-0.885), mortality (RR 0.830, 95% CI 0.775-0.888), GI hemorrhage (RR 0.566, 95% CI 0.439-0.730), and cardiac arrest (RR 0.696, 95% CI 0.531-0.911). We found no significant difference in the risk of ischemic stroke (RR 1.024, 95% CI 0.744-1.408), intracranial hemorrhage (RR 0.587, 95% CI 0.270-1.280), systemic embolism (RR 0.828 (95% CI 0.512-1.339), or other cardiac arrythmias (RR 0.973, 95% CI 0.804-1.179). Conclusion: In individuals with AF and ESRD the use of rivaroxaban, in comparison to warfarin, was associated with a reduction in the risk of mortality, gastrointestinal hemorrhage, and cardiac arrest. We found no difference in other clinically relevant outcomes, including ischemic stroke. These findings suggest an extension of the safety benefits previously observed with DOACs to the ESRD population, however further research is needed to guide management.

Comparing Major Bleeding Risk in Outpatients With Atrial Fibrillation or Flutter by Oral Anticoagulant Type (from the National Cardiovascular Disease Registry's Practice Innovation and Clinical Excellence Registry)

Rivaroxaban Versus Warfarin in African American Patients with Nonvalvular Atrial Fibrillation

To compare outcomes of patients who underwent left atrial appendage occlusion (LAAO) for nonvalvular atrial fibrillation (NVAF) and contraindication to anticoagulants due to history of either gastrointestinal (GI) or intracranial (IC) bleeding. Patients with NVAF that underwent LAAO for GI or IC bleeding from seven centers were included in this observational study. Baseline characteristics, procedural features, and follow-up data were collected, and compared between the two groups. The primary outcomes were incidence of ischemic and hemorrhagic events at 12-month. Six hundred twenty-eight patients were included, 57% with previous GI-bleeding, and 43% with previous IC-bleeding. Median CHA 2 DS 2-VASc score was 4 (interquartile range[IQRs]: 3-5) for both GI-bleeding and IC-bleeding patients, while GI-bleeding patients had a higher HAS-BLED score (4 [IQRs: 3-4] vs. 3 [IQRs]: 2-3]; p = 0.001). At 12-month follow-up, relative risk reduction for stroke was similar between the two groups. The GI-bleeding group had more hemorrhagic events compared to IC-bleeding group (any bleeding 8.4% vs. 3.2%; p = 0.012; major bleeding BARC 3-5: 4.3% vs. 1.8; p = 0.010). At multivariate analysis history of GI bleeding was an independent predictor of hemorrhagic events (adjusted HR: 2.39, 95% confidence interval:1.02-5.63; p = 0.047). Outcomes after LAAO may be affected by the different indications for the procedure. In our study,GI-bleeding and IC-bleeding as indication to LAAO differ in their baseline characteristics. LAAO confirms its efficacy in ischemic risk reduction in both groups, while GI bleeding seems to be an independent predictor of bleeding recurrence at 12 months behind the antithrombotic regimen.

Dabigatran and rivaroxaban are non-vitamin K oral anticoagulants approved for stroke prevention in patients with nonvalvular atrial fibrillation (AF). There are no randomized head-to-head comparisons of these drugs for stroke, bleeding, or mortality outcomes. To compare risks of thromboembolic stroke, intracranial hemorrhage (ICH), major extracranial bleeding including major gastrointestinal bleeding, and mortality in patients with nonvalvular AF who initiated dabigatran or rivaroxaban treatment for stroke prevention. Retrospective new-user cohort study of 118 891 patients with nonvalvular AF who were 65 years or older, enrolled in fee-for-service Medicare, and who initiated treatment with dabigatran or rivaroxaban from November 4, 2011, through June 30, 2014. Differences in baseline characteristics were adjusted using stabilized inverse probability of treatment weights based on propensity scores. The data analysis was performed from May 7, 2015, through June 30, 2016. Dabigatran, 150 mg, twice daily; rivaroxaban, 20 mg, once daily. Adjusted hazard ratios (HRs) for the primary outcomes of thromboembolic stroke, ICH, major extracranial bleeding including major gastrointestinal bleeding, and mortality, with dabigatran as reference. Adjusted incidence rate differences (AIRDs) were also estimated. A total of 52 240 dabigatran-treated and 66 651 rivaroxaban-treated patients (47% female) contributed 15 524 and 20 199 person-years of on-treatment follow-up, respectively, during which 2537 primary outcome events occurred. Rivaroxaban use was associated with a statistically nonsignificant reduction in thromboembolic stroke (HR, 0.81; 95% CI, 0.65-1.01; P = .07; AIRD = 1.8 fewer cases/1000 person-years), statistically significant increases in ICH (HR, 1.65; 95% CI, 1.20-2.26; P = .002; AIRD = 2.3 excess cases/1000 person-years) and major extracranial bleeding (HR, 1.48; 95% CI, 1.32-1.67; P < .001; AIRD = 13.0 excess cases/1000 person-years), including major gastrointestinal bleeding (HR, 1.40; 95% CI, 1.23-1.59; P < .001; AIRD = 9.4 excess cases/1000 person-years), and with a statistically nonsignificant increase in mortality (HR, 1.15; 95% CI, 1.00-1.32; P = .051; AIRD = 3.1 excess cases/1000 person-years). In patients 75 years or older or with CHADS2 score greater than 2, rivaroxaban use was associated with significantly increased mortality compared with dabigatran use. The excess rate of ICH with rivaroxaban use exceeded its reduced rate of thromboembolic stroke. Treatment with rivaroxaban 20 mg once daily was associated with statistically significant increases in ICH and major extracranial bleeding, including major gastrointestinal bleeding, compared with dabigatran 150 mg twice daily.

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