Oral anticoagulants and antiplatelets compared for risk of recurrent VTE, major bleeds

All oral anticoagulants and antiplatelet agents reduced recurrence of venous thromboembolism (VTE) compared with placebo, with aspirin reducing risk the least and vitamin K antagonists reducing it the most, a meta-analysis found.

Researchers conducted a meta-analysis of 12 randomized, controlled studies from the published literature. Results were published online Aug. 30 by BMJ.

In the efficacy study population of 11,999 patients, all treatments reduced the risk of recurrent VTE. Vitamin K antagonists, given at a standard adjusted dose, defined as a target international normalized ratio of 2.0 to 3.0, showed the highest risk difference (odds ratio [OR], 0.07; 95% credible interval [CrI], 0.03 to 0.15) and aspirin showed the lowest risk difference (OR, 0.65; 95% CrI, 0.39 to 1.03) compared with placebo or observation groups.

Risk of major bleeding was higher with a standard adjusted dose of vitamin K antagonists (OR, 5.24; 95% CrI, 1.78 to 18.25) compared to placebo or observation groups. Also, among the 12,167 patients evaluated for safety, there was an increased risk of major bleeding associated with rivaroxaban and low-intensity vitamin K antagonists compared with placebo or observation.

Apixaban, 5 mg twice daily, had the highest probability (69%) of being the best treatment for reducing the risk of major bleeding events among all treatments. That regimen was associated with a reduction in major bleeding compared with standard adjusted-dose vitamin K antagonists, dabigatran, rivaroxaban (OR, 0.01; 95% CrI, 0.00001 to 0.4), and low-intensity vitamin K antagonists (OR, 0.04; 95% CrI, 0.0009 to 0.53).

After one trial was excluded, 16 (0.13%) of 12,090 patients had a fatal recurrent VTE; of these, nine had received placebo or observation. Five (0.04%) of 11,765 patients had a fatal bleeding episode; of these, four had received placebo or observation. There were no differences among treatments in fatal recurrent VTE or fatal bleeding events.

The researchers noted that risks for recurrent VTE and major bleeding are key pieces of information when doctors consider agents for secondary prevention. They wrote, “The rates of recurrent VTE and major bleeding events should be taken into account when assessing the efficacy and safety of different treatment strategies for secondary prevention for VTE. Other factors—including individual patient risk factors, case fatality, costs, lifestyle modifications, burden of laboratory monitoring, and patient values and preferences—should also be considered when making recommendations to patients regarding anticoagulant treatment.”