ROCKET AF Substudy: Rivaroxaban Safe, Effective in East Asian Patients

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Patients of East Asian descent reap the same stroke-prevention benefit from rivaroxaban as others with nonvalvular atrial fibrillation (A-fib), according to a substudy of the ROCKET AF trial published online April 24, 2014, ahead of print in Stroke.

ROCKET AF, published in the New England Journal of Medicine in 2011, randomized 14,264 patients with nonvalvular A-fib to once daily rivaroxaban (20 or 15 mg) or dose-adjusted warfarin (target international normalized ratio [INR] 2.0-3.0). In the main efficacy analysis, the novel oral anticoagulant was noninferior to warfarin for the primary efficacy endpoint of stroke (ischemic or hemorrhagic) or systemic embolism.

For the secondary analysis, Ka Sing Lawrence Wong, MD, of Prince of Wales Hospital (Hong Kong, China), and colleagues compared the occurrence of the primary endpoint in the subgroup of 932 patients (6.5%) classified as East Asian vs the 13,322 patients who were not. East Asian patients were those originating from China (n = 496), Korea (n = 204), Taiwan (n = 159), or Hong Kong (n = 73). No patients from Japan were enrolled in ROCKET AF.

No Differences in Stroke, Major Bleeding

While the annual event rates for the primary efficacy endpoint were numerically higher in both the rivaroxaban and warfarin arms of the East Asian subgroup (2.6% and 3.4% per year, respectively) compared with the remaining ROCKET AF population (2.1% and 2.4% per year, respectively), there was no interaction between treatment and East Asian or non-East Asian status (interaction P = .666). In addition, there were no differences in rates of the 2 prespecified composite secondary efficacy endpoints (stroke, non-CNS systemic embolism, and vascular death and stroke, non-CNS systemic embolism, MI, and vascular death).

Compared with the remaining ROCKET AF population, there was a strong trend toward increased stroke or systemic embolism in the East Asian cohort irrespective of treatment assignment (HR 1.34; 95% CI 1.00-1.80; P = .053). Annual rates of all-cause stroke, hemorrhagic stroke, ischemic stroke, nondisabling stroke, and disabling stroke also were higher in the East Asian cohort. However, there was no interaction between East Asian or non-East Asian status, suggesting that the relative efficacy of rivaroxaban vs warfarin for those outcomes was consistent between the 2 cohorts.

The risk of major or nonmajor clinically relevant bleeding (the principal safety outcome) was also higher in East Asian patients than the rest of the population irrespective of treatment assignment (HR 1.42; 95% CI 1.25-1.62; P < .0001). However, there was no difference in major bleeding rates between those residing within vs outside East Asia irrespective of treatment assignment (HR 1.23; 95% CI 0.94-1.60; P =.14).

Importantly, compared with warfarin, rivaroxaban was associated with less critical organ bleeding (HR = 0.28; 95% CI 0.10-0.75) and intracranial hemorrhage (HR = 0.24; 95% CI 0.08-0.71) in the East Asian cohort, with a strong interaction between treatment and residence within or outside East Asia for intracranial hemorrhage (interaction P = .044).

Safety in East Asians Confirmed

In an accompanying editorial, Masahiro Yasaka, MD, PhD, of Kyushu Medical Center (Fukuoka, Japan), and Gregory Y.H. Lip, MD, of the University of Birmingham Centre for Cardiovascular Sciences (Birmingham, United Kingdom), say the results in the East Asian cohort of ROCKET AF are consistent with those seen in the Japanese Rivaroxaban Once Daily

Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (J ROCKET). Both trials, they say, “clearly demonstrated similar efficacy and safety of rivaroxaban versus warfarin among patients within and outside East Asia.”

Historically, vitamin K antagonists have been associated with higher risk for intracranial bleeding, major hemorrhage, and stroke, as well as difficulties in maintaining time in therapeutic range among Asian patients, they note. There has also been uncertainty over the optimal target INR range in Asians, which was perceived to be lower than the range typically recommended in non-Asians.

“In summary, Asians seem to do poorly on [vitamin K antagonists] with lower efficacy, poorer safety, and more intracranial bleeding when compared with non-Asians,” they write. “Therefore,

[novel oral anticoagulants], whether dabigatran, rivaroxaban, apixaban, or (when licensed) edoxaban would seem the best option for stroke prevention in treating Asian patients with nonvalvular [A-fib].”

Study Details

East Asian patients were younger and had lower body weight, creatinine clearance, and prior vitamin K antagonist use but higher prevalence of prior stroke at baseline than the non-East Asian cohort. They also had less congestive heart failure, hypertension, or previous MI.

 

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Sources:
1. Wong KSL, Hu DY, Oomman A, et al. Rivaroxaban for stroke prevention in East Asian patients from the ROCKET AF Trial. Stroke. 2014;Epub ahead of print.

2. Yasaka M, Lip GYH. Stroke prevention in Asian patients with atrial fibrillation [editorial]. Stroke. 2014;Epub ahead of print.

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