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

Aims: Heart 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 Results: Using 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 CHA DS -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).

Conclusions: Effectiveness 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.