https://immattersacp.org/weekly/archives/2013/12/10/6.htm

New oral anticoagulants may slightly decrease all-cause mortality when compared to warfarin, meta-analysis suggests

In patients with atrial fibrillation, the advantages of all 4 new oral anticoagulants over warfarin seem to outweigh the risks, a new meta-analysis found.


In patients with atrial fibrillation, the advantages of all 4 new oral anticoagulants over warfarin seem to outweigh the risks, a new meta-analysis found.

Researchers searched Medline between Jan. 1, 2009, and Nov. 19, 2013, for phase 3 trials of atrial fibrillation patients who were randomized to take new oral anticoagulants (n=42,411) or warfarin (n=29,272). Included trials also reported both safety and efficacy outcomes. The new oral anticoagulants were dabigatran (110 mg and 150 mg), rivaroxaban, apixaban and edoxaban (30 mg and 60 mg). The main outcomes were stroke and systemic embolic events, hemorrhagic stroke, ischemic stroke, myocardial infarction, major bleeding, gastrointestinal bleeding, intracranial hemorrhage, and all-cause death. Results were published online Dec. 4 by Lancet.

Patients who took the new drugs had 19% fewer strokes or systemic embolic events than those who took warfarin (relative risk [RR], 0.81; 95% CI, 0.73 to 0.91; P<0.0001). This result was due in large part to a reduction in hemorrhagic stroke (RR, 0.49; 95% CI, 0.38 to 0.64; P<0.0001). Patients who took the new oral anticoagulants also had less all-cause mortality (RR, 0.90; 95% CI, 0.85 to 0.95; P=0.0003) and intracranial hemorrhage (RR, 0.48; 95% CI, 0.39 to 0.59; P<0.0001); however, they had greater gastrointestinal bleeding (RR, 1.25; 95% CI, 1.01 to 1.55; P=0.04). Patients on the 2 low-dose new anticoagulant regimens had a better bleeding profile but more ischemic strokes than those taking warfarin, and their overall reduction in stroke or systemic embolic events wasn't significantly different from warfarin (RR, 1.03; 95% CI, 0.84 to 1.27; P=0.75).

This meta-analysis “support(s) the premise that compared with warfarin, new oral anticoagulants, as a class, reduce all-cause mortality by about 10% …,” the authors wrote. The analysis doesn't answer the question of which new drug is best, an editorial noted, suggesting that “ultimately, the drug could be fitted to the patient, or the patient to the drug, dependent on a focus on safety or efficacy, and on other patient factors, such as renal function and drug compliance.”

Researchers in a second study sought to determine the long-term safety and efficacy of edoxaban compared to warfarin in 21,105 patients with moderate- to high-risk atrial fibrillation and followed patients for a median of 2.8 years. They found that both drugs didn't differ significantly in terms of stroke or systemic embolism but that edoxaban was associated with significantly lower rates of major bleeding (3.43% with warfarin vs. 2.75% with high-dose edoxaban and 1.61% with low-dose edoxaban; hazard ratios, 0.80 and 0.47; P<0.001 for both comparisons). Edoxaban patients also had lower mortality from cardiovascular causes (3.17% vs. 2.74% and 2.71%; hazard ratios, 0.86 and 0.85; P=0.01 for both comparisons). The study was published Nov. 28 by the New England Journal of Medicine.

A third study reported additional results from the ROCKET AF trial (which found that rivaroxaban and warfarin carried similar risks for stroke/systemic embolism and major/nonmajor clinically relevant bleeding). The new analysis focused on factors that placed patients at greater risk for major bleeding, regardless of whether they took rivaroxaban or warfarin. The risk factors were older age, current or prior smoking, male sex, mild anemia, diastolic blood pressure of at least 90 mm Hg, prior gastrointestinal bleeding, and aspirin use at baseline. The study was published online Dec. 4 by the Journal of the American College of Cardiology.