Rivaroxaban In Non-valvular Atrial Fibrillation Patients Research Articles

Clinical impact of switching or continuation of apixaban or rivaroxaban among patients with non-valvular atrial fibrillation

Abstract Background Numerous studies have demonstrated varied clinical outcomes with initiation of different direct oral anticoagulants (DOACs) among patients with non-valvular atrial fibrillation (NVAF). Although switching of DOACs either for medical or non-medical reasons occurs among some NVAF patients in real-world clinical practice, there has been a lack of evidence on the clinical outcomes of those switchers. Purpose Assess the risk of stroke/systemic embolism (SE) and major bleeding (MB) among NVAF patients who switched from apixaban therapy to rivaroxaban or switched from rivaroxaban therapy to apixaban. Methods This retrospective study identified NVAF patients who initiated the most commonly used DOACs (apixaban or rivaroxaban) between 01 Jan 2013 and 31 December 2021 using a large US administrative claims database (Optum’s de-identified Clinformatics® Data Mart Database) representing patients in commercial or Medicare Advantage insurance plans. Patients who switched from one DOAC to the other within 30 days before or 90 days after discontinuation of initial DOAC and patients who continued receiving the initial DOAC were included. For switchers, the switch date was the index date. For continuers, a hypothetic index date was randomly assigned based on the distribution of the time from initial DOAC prescription to the switch date in the switchers group. Two final cohorts (switchers and continuers) within apixaban initiators and rivaroxaban initiators were further propensity score matched (PSM) based on pre-index characteristics up to a 1:5 ratio. The risks of stroke/SE and MB after the index date were compared between patients who continued the initial DOAC and patients who switched to the other DOAC. Results There were 167,868 apixaban initiators and 65,888 rivaroxaban initiators. After PSM, 2,884 patients who switched from apixaban to rivaroxaban were matched to 14,296 patients who continued apixaban, and 2,853 patients who switched from rivaroxaban to apixaban were matched to 13,330 patients who continued rivaroxaban. Patient characteristics were balanced between the continuers and switchers for both apixaban and rivaroxaban initiators. Patients who switched from apixaban to rivaroxaban were associated with a higher risk of stroke/SE (Hazard Ratio (HR):1.54, 95% Confidence Interval (CI): 1.06-2.24) and MB (HR: 1.73, 95% CI: 1.40-2.14) than those who continued apixaban. Patients who switched from rivaroxaban to apixaban were associated with a similar risk of stroke/SE (HR:0.75, 95% CI: 0.45-1.24) and a lower risk of MB (HR:0.58, 95%CI: 0.44-0.76) compared to those who continued rivaroxaban. Conclusion Bleeding outcomes associated with switching or continuation of apixaban or rivaroxaban in NVAF patients were consistent with existing evidence supporting a better safety profile for apixaban vs rivaroxaban.

Effectiveness and Safety of Rivaroxaban Versus Warfarin among Nonvalvular Atrial Fibrillation Patients with Concomitant Obstructive Sleep Apnea

Background Obstructive sleep apnea (OSA) is associated with an increased incidence of atrial fibrillation (AF), hypertension, diabetes, heart failure, coronary heart disease, stroke, and death. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular AF (NVAF) patients with concomitant OSA. Methods This was an analysis of electronic health record (EHR) data from November 2010 to December 2021. We included adults with NVAF and OSA at baseline, newly initiated on rivaroxaban or warfarin, and with ≥12 months of prior EHR activity. Patients with valvular disease, alternative indications for oral anticoagulation, or who were pregnant were excluded. The incidence rates of developing stroke or systemic embolism (SSE) and bleeding-related hospitalization were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using propensity score-overlap weighted proportional hazards regression. Multiple sensitivity and subgroup analyses were performed. Results We included 21,940 rivaroxaban (20.1% at the 15 mg dose) and 38,213 warfarin (time-in-therapeutic range = 47.3 ± 28.3%) patients. Rivaroxaban was found to have similar hazard of SSE compared to warfarin (HR = 0.92, 95% CI = 0.82-1.03). Rivaroxaban was associated with a reduced rate of bleeding-related hospitalizations (HR = 0.85, 95% CI = 0.78-0.92) versus warfarin, as well as reductions in intracranial (HR = 0.76, 95% CI = 0.62-0.94) and extracranial (HR = 0.89, 95%CI = 0.81-0.97) bleeding. Upon sensitivity analysis restricting the population to men with a CHA 2 DS 2 VASc score ≥2 or women with a score ≥3, rivaroxaban was associated with a significant 33% risk reduction in SSE and 43% reduction in the risk of bleeding-related hospitalization. No significant interaction for the SSE or bleeding-related hospitalization outcomes was observed upon subgroup analyses. Conclusion Among patients with NVAF and OSA, rivaroxaban had similar SSE risk versus warfarin but was associated with reductions in any intracranial and extracranial bleeding-related hospitalizations. Rivaroxaban was associated with significant reductions in SSE and bleeding-related hospitalizations when the study population was restricted to patients with a moderate-to-high risk of SSE. These data should provide prescribers with additional confidence in selecting rivaroxaban in NVAF patients who have OSA at the time of anticoagulation initiation.

Effectiveness and safety of rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation and heart failure.

AimsHeart failure (HF) is a common co‐morbidity in non‐valvular atrial fibrillation (NVAF) patients and a potent risk factor for stroke, bleeding, and a decreased time‐in‐therapeutic range with warfarin. We assessed the real‐world effectiveness and safety of rivaroxaban and warfarin in NVAF patients with co‐morbid HF.Methods and resultsUsing US Truven MarketScan Commercial and Medicare supplemental database claims data from 11/2011 to 12/2016, we identified oral anticoagulant (OAC)‐naïve NVAF patients with HF (International Classification of Diseases, 10th Revision codes of I50 or I09.81) and ≥12 months of insurance coverage prior to the qualifying OAC dispensing. Rivaroxaban users (20 or 15 mg once daily) were 1:1 propensity score matched to warfarin users, with residual absolute standardized differences <0.1 being achieved for all covariates after matching. Patients were followed up until an event, OAC discontinuation/switch, insurance disenrolment, or end of follow‐up. Rates [events per 100 person‐years (PYs) of follow‐up] for stroke or systemic embolism and major bleeding (using the Cunningham algorithm) were compared between the matched cohorts using Cox proportion hazard regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). We matched 3418 rivaroxaban (32% receiving the reduced dose) and 3418 warfarin users with NVAF and HF with a median (interquartile range) available follow‐up of 1.4 (0.6, 2.5) years. Median age was 74 (63, 82) years, and median CHA2DS2‐VASc and HASBLED scores were 4 (3, 5) and 2 (2, 3). Common HF medications included beta‐blockers (64%), angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers (62%), loop diuretics (46%), digoxin (11%), and aldosterone receptor antagonists (10%). The hazard of developing stroke or systemic embolism (0.98 events/100PY vs. 1.28 events/100PY; HR = 0.82, 95% CI = 0.47–1.44), ischaemic stroke (0.70 events/100PY vs. 1.02 events/100PY; HR = 0.77, 95% CI = 0.41–1.46), or major bleeding (3.86 events/100PY vs. 4.23 events/100PY; HR = 0.98, 95% CI = 0.73–1.31) was not found to be different between rivaroxaban and warfarin users. Intracranial haemorrhage was infrequent in both cohorts and numerically less with rivaroxaban (0.27 events/100PY vs. 0.36 events/100PY; HR = 0.73, 95% CI = 0.25–2.08).ConclusionsEffectiveness and safety of rivaroxaban vs. warfarin are sustained in NVAF patients with co‐morbid HF treated in routine practice. The general consistency between this real‐world study and those from phase III randomized trial data of rivaroxaban should provide additional reassurance to clinicians regarding the use of rivaroxaban in NVAF patients with HF.

Study Design and Baseline Characteristics of the EXPAND Study: Evaluation of Effectiveness and Safety of Xa Inhibitor, Rivaroxaban for the Prevention of Stroke and Systemic Embolism in a Nationwide Cohort of Japanese Patients Diagnosed as Non-Valvular Atrial Fibrillation.

The use of rivaroxaban, a factor Xa inhibitor, has been increasing for prevention of ischemic stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) in Japan. We conducted the nationwide multicenter study, termed as the EXPAND Study, to address its effectiveness and safety in the real-world practice of patients with non-valvular AF in Japan. The EXPAND Study is a prospective, non-interventional, observational cohort study to evaluate the effectiveness and safety of rivaroxaban in non-valvular AF patients in a real-world clinical practice. A total of 7,178 patients with non-valvular AF were enrolled in 684 medical institutes between November 20, 2012 and June 30, 2014. As for the baseline demographic and clinical characteristics of 7,164 patients, the proportion of female patients was 32.2%, and those of patients with creatinine clearance < 50 mL/min and non-paroxysmal (persistent or permanent) AF were 21.8% and 55.1%, respectively. The proportions of patients complicated with hypertension, congestive heart failure, diabetes mellitus, and a history of ischemic stroke were 70.9%, 25.9%, 24.3%, and 20.2%, respectively. The proportions of patients with a CHADS2 score ≤ 1 and a CHA2DS2-VASc score ≤ 1 were 37.3% and 13.6%, respectively. They were followed up until March 31, 2016 for a mean follow-up period of approximately 2.5 years. The findings of the EXPAND Study will help to establish an appropriate treatment with rivaroxaban for Japanese patients with non-valvular AF.