New Oral Anticoagulants in Addition to Dual Anti-platelet Therapy After an Acute Coronary Syndrome: A Systematic Review of Randomized Controlled Trials

BACKGROUND: Despite important advances in the treatment of acute coronary syndrome (ACS), the risk of recurrent ischemic events remains high. This generates interest for improved antithrombotic therapy in addition to the current standard management of dual anti-platelet therapy. OBJECTIVES: This study aimed to evaluate randomized controlled trials on the efficacy and safety of new oral anticoagulants (NOACs) compared with placebo in patients receiving dual anti-platelet therapy after an ACS. METHODS: An engine search using Pub Med database, Cochrane Central Registry of Controlled trials and Clinicaltrials.gov was conducted to search for randomized, placebo-controlled trials evaluating the efficacy and safety of NOACs in addition to dual anti-platelet therapy after ACS. Included studies were included in a meta-analysis, evaluating the effect of NOACs on the following endpoints: recurrence of myocardial infarction and severe ischemia; cardiovascular death; ischemic stroke; stent thrombosis; and bleeding based on Thrombolysis in Myocardial Infarction scheme. RESULTS: Six randomized-placebo controlled trials were included in the analysis, involving 31,264 patients. Compared with placebo, addition of NOACs to dual anti-platelet therapy after ACS was associated with a statistically significant decrease in the recurrence of myocardial infarction and severe ischemia (RR 0.90; 95% CI 0.82-1.00; p=0.041); stent thrombosis (RR 0.71; 95% CI 0.56-0.91; p=0.007); and ischemic stroke (RR 0.79; 95% CI 0.64-0.97; p=0.025). There was also a trend towards decreased cardiovascular death (RR 0.86; 95% CI 0.74-1.00; p=0.057). However, a significantly increased bleeding rate was noted (RR 2.26; CI 2.03-2.50, p<0.001). CONCLUSION: The addition of NOACs on top of dual anti-platelet therapy in patients with ACS was associated with a significant decrease in ischemic event, stent thrombosis and ischemic stroke, with a trend towards lesser incidence of cardiovascular death. However, its efficacy was limited by higher bleeding episodes.