December 06, 2013
5 min read

New oral anticoagulants show favorable safety, efficacy vs. warfarin

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A large meta-analysis indicated a favorable risk-benefit profile for the new oral anticoagulants and significant reductions in stroke, intracranial hemorrhage and mortality as compared with warfarin.

The new oral anticoagulants were associated with similar major bleeding as with warfarin, but more gastrointestinal bleeding, according to the report.

The meta-analysis included the 71,683 participants included in the RE-LY study of dabigatran (Pradaxa, Boehringer Ingelheim), ROCKET AF study of rivaroxaban (Xarelto, Janssen Pharmaceuticals), ARISTOTLE study of apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) and ENGAGE AF-TIMI 48 study of edoxaban (Lixiana, Daiichi Sankyo). Edoxaban is not yet approved by the FDA.

The researchers’ goal was to assess the safety and efficacy of the drugs vs. warfarin for the prevention of stroke in patients with atrial fibrillation. Median follow-up in the trials ranged from 1.8 to 2.8 years. The primary outcomes were incidence of stroke and systemic embolic events, MI, major and GI bleeding, intracranial hemorrhage and all-cause mortality.

Overall, 42,411 participants received an oral anticoagulant and 29,272 received warfarin.

The oral anticoagulants were associated with significant reductions in the incidence of stroke or systemic embolic events (RR=0.81; 95% CI, 0.73-0.91), which was driven primarily by a reduction in hemorrhagic stroke (RR=0.49; 95% CI, 0.38-0.64). Both all-cause mortality (RR=0.9; 95% CI, 0.85-0.95) and intracranial hemorrhage (RR=0.48; 95% CI, 0.39-0.59) were also significantly reduced among recipients of the oral anticoagulants. However, GI bleeding was increased with the oral anticoagulants (RR=1.25; 95% CI, 1.01-1.55).

Subgroup analysis according to age, sex, diabetes status, stroke history, creatinine clearance and time in the therapeutic range yielded similar results to the main analysis, with the exception that patients who achieved a center-based time in therapeutic range below 66% had a greater relative reduction of major bleeding than those with time above 66%.

A separate meta-analysis of low-dose oral anticoagulant regimens in two studies indicated similar reductions in stroke or systemic embolic events compared with warfarin (RR=1.03; 95% CI, 1.03-0.84) as well as a favorable bleeding risk profile (RR=0.65; 95% CI, 0.43-1). However, ischemic ischemic stroke was increased with low-dose oral anticoagulants (RR=1.28; 95% CI, 1.02-1.6).

“This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation,” the researchers concluded. “The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population.”

Disclosure: See the full study for a list of the researchers’ relevant financial disclosures.