A month-by-month analysis of direct oral anticoagulants for secondary prevention of acute coronary syndrome

Direct oral anticoagulants in addition to antiplatelet therapy have been developed for secondary prevention of acute coronary syndrome (ACS), but it remains unclear how its effects change in the follow-up period.1 A previous meta-analysis evaluated six randomized controlled trials using direct oral anticoagulants for secondary prevention of ACS until 1 March 2017.1 Then we included three trials (Apixaban for Prevention of Acute Ischemic Events; ATLAS Anti-Xa Therapy to Lower cardiovascular events in addition to Aspirin with or without thienopyridine therapy in Subjects with Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction 46 [ACS-TIMI 46] and Anti-Xa Therapy to Lower cardiovascular events in Addition to standard therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51 [ATLAS ACS 2-TIMI 51]) reporting Kaplan–Meier curves and re-calculated their hazard ratios and 95% confidence intervals by month, according to a recent method.2–5 Apixaban was not effective in reducing the composite events of cardiovascular death, myocardial infarction and stroke in patients with ACS during the whole follow-up period (Figure 1). Rivaroxaban began to reduce the composite events from the third month, which lasted until the sixth month in the ATLAS ACS-TIMI 46 trial. In contrast, the effects of rivaroxaban were U-shaped in the ATLAS ACS 2-TIMI 51 trial, with its effects becoming insignificant from the eighth month to the fifteenth month. Considering the substantial increase of major bleeding and intracranial hemorrhage during the follow-up period, a twice-daily 2.5 mg dose of rivaroxaban may be cautiously used in the short term (≤6 months) in ACS patients with high ischemic risk and low bleeding risk.6 A month-by-month analysis of apixaban and rivaroxaban for reducing the composite endpoints of cardiovascular death, myocardial infarction and stroke in patients with acute coronary syndrome. APPRAISE: Apixaban for Prevention of Acute Ischemic Events; ATLAS ACS-TIMI 46: Anti-Xa Therapy to Lower cardiovascular events in addition to Aspirin with or without thienopyridine therapy in Subjects with Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction 46; ATLAS ACS 2-TIMI 51: Anti-Xa Therapy to Lower cardiovascular events in Addition to standard therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51; CI: confidence interval; ES: Effect size. In conclusion, short-term rivaroxaban in addition to antiplatelet therapy is effective in reducing the composite endpoints of cardiovascular death, myocardial infarction and stroke in ACS patients. Apixaban may not be an optimal choice for ACS patients. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The author(s) received no financial support for the research, authorship, and/or publication of this article.