Safety and Efficacy of Direct Oral Anticoagulant in Addition to Antiplatelet Therapy After Acute Coronary Syndrome: A Systemic Review and Meta-analysis of 53,869 Patients

Introduction: Significant progress has been made in the management of patients with acute coronary syndrome (ACS) during the past few decades. However, the role of direct oral anticoagulants (DOACs) in post-ACS prophylactic therapy remains unknown. This study aims to assess the efficacy and safety of DOACs plus antiplatelet treatment (APT) after ACS.

Methods: A systematic literature search was conducted to identify randomized clinical trials comparing DOACs plus APT with APT alone after ACS. The primary efficacy end points were cardiovascular mortality, myocardial infarction, all-cause mortality, and stroke and systemic embolization (SSE). The primary safety end point was major bleeding. The random-effects model was used to calculate relative risk (RR) and corresponding 95% CIs.

Results: Nine trials with a total of 53,869 patients were identified, with 33,011 (61.2%) in the DOACs plus APT group and 20,858 (38.8%) in the APT alone group. The use of DOACs did not decrease the risk of cardiovascular death (RR = 0.87; 95% CI, 0.75-1.01; P = 0.08; I² = 0%) or myocardial infarction (RR = 0.90; 95% CI, 0.80-1.02; P = 0.10; I² = 6%). However, the risk of SSE was significantly lower in patients who received DOACs plus APT compared with APT alone (RR = 0.67; 95% CI, 0.50-0.90; P = 0.008). Moreover, all-cause mortality was significantly lower in the DOACs plus APT group (RR = 0.83; 95% CI, 0.71-98; P = 0.03; I² = 0%). However, the risk of major bleeding was significantly higher in patients treated with DOACs plus APT compared with APT alone (RR = 2.53; 95% CI, 1.96-3.26; P < 0.01; I² = 0%), as was the risk of nonmajor bleeding (RR = 2.27; 95% CI, 1.51-3.41; P < 0.01).

Implications: DOACs plus APT for the prevention of left ventricular thrombus in patients with ACS were associated with a lower risk of SSE and all-cause mortality but increased the risk of major and nonmajor bleeding. The benefits and risks of this approach should be weighed based on a patient's individual clinical characteristics.