ROCKET AF: Heart Failure Does Not Weaken the Case for Rivaroxaban

Download this article's Factoid (PDF & PPT for Gold Subscribers)

In patients with nonvalvular atrial fibrillation (A-fib), rivaroxaban stands as a valid alternative to warfarin regardless of heart failure status, according to findings derived from the ROCKET AF trial, published online May 30, 2013, ahead of print in Circulation: Heart Failure.

ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation), published in the New England Journal of Medicine in 2011, randomized 14,264 patients to fixed-dose rivaroxaban (20 mg daily or 15 mg daily) or dose-adjusted warfarin (target international normalized ratio 2.0-3.0). The study’s main efficacy analysis of the per-protocol population found rivaroxaban to be noninferior to warfarin for the primary endpoint of stroke or systemic embolism.

For the current analysis, Sean van Diepen, MD, MSc, of the University of Alberta Hospital (Edmonton, Canada), examined outcomes for the trial’s 9,033 patients (63.7%) with a history of heart failure or low ejection fraction (< 40%). Among them, 50.1% were randomized to rivaroxaban and 49.9% to warfarin; within the warfarin group, the mean time in therapeutic range (TTR) was 53% in patients with heart failure and 59% in those without.

Regardless of drug assignment, heart failure patients had similar levels of persistent A-fib, ejection fraction < 40%, previous vitamin K antagonist use, and concurrent aspirin use as well as similar mean CHADS₂ scores.

Heart Failure Worsens Outcomes Across the Board

Heart failure patients tended to be younger, more likely to have persistent A-fib, and have higher mean CHADS₂ scores compared with their peers without heart failure. Overall, patients with heart failure had higher risks of all-cause death, vascular death, and the composite of stroke, systemic embolism, or vascular death—but not stroke and systemic embolism—compared with their peers who lacked the condition.

Irrespective of whether patients did or did not have heart failure, however, the combined rate of stroke and systemic embolism (primary efficacy analysis) by intention-to-treat was equivalent for rivaroxaban and warfarin as was major/nonmajor clinically relevant bleeding (primary safety analysis; table 1).

Table 1. Outcomes by Heart Failure/Treatment Arm: Events per 100 Person-Years

Among heart failure patients, hemorrhagic stroke was reduced with rivaroxaban vs. warfarin (0.16 vs. 0.43 events per 100-person years; adjusted HR 0.38; 95% CI 0.19-0.76). While patients without heart failure saw no such benefit, the interaction between heart failure and treatment arm failed to reach statistical significance for this endpoint (P for interaction = 0.067).

Subgroup analyses in the heart failure cohort showed consistent efficacy for rivaroxaban that did not depend on LVEF, New York Heart Association Class, or CHADS₂ score.

Rivaroxaban Fills a Need

According to Dr. van Diepen and colleagues, both A-fib and heart failure guidelines recommend the use of vitamin K antagonists to reduce thromboembolic risk. Yet heart failure is known to reduce TTR with such drugs, and as a consequence, patients receiving vitamin K antagonists “may be predisposed to reduced efficacy and increased bleeding.

“Rivaroxaban, an oral factor Xa inhibitor, has a predictable pharmacokinetic profile and dual clearance pathways, renal and hepatic,” they continue, noting that the novel anticoagulant “represents a theoretically attractive alternative” in A-fib and heart failure patients. With increasing prevalence of both conditions, a growing number of patients will require thromboembolic prophylaxis, the researchers add.

Importantly, they say, subgroup analyses indicate that “the benefit of rivaroxaban over warfarin extends to [heart failure] patients with [A-fib] irrespective of the definition of [heart failure], severity of symptoms, or thromboembolic risk.”

 

---

Source:
van Diepen S, Hellkamp AS, Patel MR, et al. Efficacy and safety of rivaroxaban in patients with heart failure and nonvalvular atrial fibrillation: Insights from ROCKET AF. Circ Heart Fail. 2013;Epub ahead of print.

 

Related Stories:

• Updated Guidelines Support New Antithrombotics as Warfarin Alternatives in A-fib
• ROCKET AF: Stopping Rivaroxaban or Warfarin Equally Harmful in A-fib Patients
• ROCKET AF Published: Rivaroxaban Matches Warfarin in Treating A-Fib Patients