Direct oral anticoagulants (DOACs) provide additional benefit to antiplatelet therapy following acute coronary syndrome (ACS)—but only for ST-segment elevation myocardial infarction (STEMI)—according to a meta-analysis in JAMA Cardiology.

Some individual trials have shown DOACs, in addition to antiplatelet therapy (APT), to be effective in reducing recurrent ischemic events and cardiovascular mortality. But according to lead author Mauro Chiarito, MD, and colleagues, those trials also demonstrated an increased bleeding risk with this approach, and none evaluated outcomes based on the type of ACS at presentation.

To address this topic, the researchers studied 29,667 patients from six trials and evaluated the composite outcome of cardiovascular death, MI and stroke, in addition to major bleeding events. Nearly half of the individuals presented with STEMI while 50.7 percent had non-ST-segment elevation ACS (NSTE-ACS).

Chiarito and coauthors found:

• In the overall study population, patients treated with DOACs and APT showed a 15 percent reduction in the composite endpoint and a 3.17-fold risk of major bleeding when compared to APT alone.
• For STEMI patients with the combination therapy, the composite endpoint was reduced by 24 percent and major bleeding risk increased by a factor of 3.45.
• For NSTE-ACS, there was a nonsignificant 8 percent reduction in risk for cardiovascular death, MI and stroke associated with DOACs. The excess bleeding risk was 2.19-fold—enough to offset the marginal benefit in preventing ischemic outcomes, according to the authors.

“To our knowledge, these findings are the first evidence to support differential treatment effects of DOAC in addition to APT according to ACS baseline clinical presentation,” Chiarito et al. wrote. “In patients with NSTE-ACS, the risk-benefit profile of DOAC appears unfavorable. Conversely, DOAC in addition to APT might represent an attractive option for patients with STEMI.”

Despite the increased bleeding risk for STEMI patients taking DOACs, the authors found the reduction in ischemic events makes that treatment course worthwhile. Specifically, it would take 63 patients being treated with DOACs plus APT to prevent one occurrence of the primary endpoint. Conversely, 96 would need to be treated for one excess bleeding event to occur.

The benefit-risk ratio was almost 1:1 in the NSTE-ACS group—130 patients to prevent one ischemic event versus 137 to produce one additional bleeding event.

“The rationale for using DOAC in patients with ACS without an indication for oral anticoagulation, especially for those with STEMI, is linked to the pivotal role of thrombin in this clinical setting,” the researchers wrote. “After an acute MI, high thrombin levels are traceable for at least 6 months and thrombin generation is inversely correlated with recurrent cardiovascular events. Therefore, the higher thrombotic burden and coagulation cascade activation during and after STEMI compared with NSTE-ACS could help to explain, at least in part, our findings.”

Differences in clinical baseline characteristics and therapeutic strategies between STEMI and NSTE-ACS could also play a role in the results and warrant further investigation, the researchers wrote.

The researchers only included major bleeding as their primary safety endpoint, while others have also included minor bleeding and clinically relevant bleeding. In addition, the studies included in the meta-analysis had different definitions of major bleeding, which could have influenced the prevalence of this endpoint.