Fewer Major Bleeds, Same Strokes, on Dabigatran vs Rivaroxaban for AF: Medicare Cohort

By Reuters Staff

October 04, 2016

NEW YORK (Reuters Health) - In elderly patients with nonvalvular atrial fibrillation (AF), dabigatran and rivaroxaban provide comparable protection against thromboembolic stroke but dabigatran is safer, according to a new analysis.

Compared with dabigatran 150 mg twice daily, rivaroxaban 20 mg once daily was associated with statistically significant increases in intracranial hemorrhage (ICH) and major extracranial bleeding, including major GI bleeding, the researchers, led by Dr. David Graham of the Center for Drug Evaluation and Research at the Food and Drug Administration, reported October 3rd in JAMA Internal Medicine.

Non-vitamin K oral anticoagulants (NOACs) are increasingly being prescribed and this study offers "valuable information for those choosing between NOACs," write Dr. Anna Parks and Dr. Rita Redberg of the University of California, San Francisco, in an editor's note.

"This study offers real-world data adding a large number of the multimorbid, older patients that constitute the rising tide of the atrial fibrillation population. The additional information should lead us to prescribe dabigatran over rivaroxaban for patients with atrial fibrillation," they conclude.

In a retrospective new-user cohort study, Dr. Graham and colleagues compared the risks of thromboembolic stroke, ICH, major extracranial bleeding and mortality in 118,891 Medicare enrollees with nonvalvular AF who initiated treatment with either dabigatran or rivaroxaban from November 2011 through the end of June 2014.

A total of 52,240 dabigatran-treated patients contributed 15,524 person-years of on-treatment follow-up, and 66,651 rivaroxaban-treated patients contributed 20,199 person-years of on-treatment follow-up. During this time, 2,537 primary outcome events occurred, including 306 thromboembolic strokes, 176 intracranial bleeding events, 1,209 major extracranial bleeding events of which 108 were GI, and 846 deaths.

Patients on rivaroxaban and dabigatran had equivalent reductions in thromboembolic stroke risk. However, rivaroxaban was associated with a statistically significant increase in ICH (hazard ratio 1.65) and major extracranial bleeding (HR 1.48), including GI bleeds (HR 1.40). There was also a statistically nonsignificant increase in death with rivaroxaban (HR 1.15).

The excess rate of ICH with rivaroxaban exceeded its reduced rate of thromboembolic stroke, the researchers report.

"Our results," they write, "are consistent with a recently published small study from Denmark that reported no difference in stroke risk but increased bleeding and mortality risks with rivaroxaban 20 mg once daily compared with dabigatran 150 mg twice daily in patients with AF."

Dr. Graham and colleagues say it's important to note that the study was restricted to patients aged 65 years or older and the comparative effects of dabigatran and rivaroxaban treatment could be different in younger populations. Also, the study examined warfarin-naive first-time users of dabigatran or rivaroxaban for stroke prevention in AF and the results could differ in patients switching from warfarin to a NOAC.

"This study represents a milestone in the next phase of NOAC research and highlights the need for more comparative effectiveness studies in this area," write Dr. Parks and Dr. Redberg.

"The current regulatory environment adds alternative anticoagulant drugs to the market without data comparing them with the current alternatives. The Patient-Centered Outcomes Research Institute can play a key role in filling in these needed data. Our choices for anticoagulation must be informed by knowledge of which agents best balance the benefits of stroke prevention with the harms of bleeding for each patient," they conclude.

The study was performed as part of the SafeRx project, a joint initiative of the Centers for Medicare & Medicaid Services (CMS) and the FDA, and was funded through an interagency agreement. The authors report no conflicts of interest.

SOURCE: http://bit.ly/2dr72e0 and http://bit.ly/2cYeEpj

JAMA Intern Med 2016.