Risk of major bleeding and major adverse cardiac events in patients with acute coronary syndrome after novel oral anticoagulants therapy: a meta-analysis

Abstract

Objective To systematically evaluate the risk of major bleeding and major adverse cardiac events(MACE) in patients with acute coronary syndrome(ACS) after combined use of novel oral anticoagulants (NOAC) and antiplatelet therapy. Methods Randomized controlled trials (RCTs) about NOAC treatment for ACS patients with basic antiplatelet therapy in related databases (up to July 2018) were searched. The outcome indicators included major bleeding events (safety indicators) and MACE (effectiveness indicators). Quality of methodology was evaluated using bias risk assessment tool of Cochrane collaboration networks. Meta-analysis was performed using RevMan 5.3 software. Results A total of 6 RCTs were entered, including comparative studies of single antiplatelet therapy (SAPT) or dual antiplatelet therapy (DAPT) combined with NOAC and combined with placebo or warfarin, involving 20 070 patients. Drugs used in the trial group included apixaban, rivaroxaban, and dabigatran etexilate. The quality evaluation showed that 4 of the 6 RCTs were with low risks of bias and 2 with high risks of bias. The meta-analysis showed that the risk of clinical major bleeding events in patients in the SAPT+ NOAC group was significantly higher than that in the SAPT+ placebo group [3.14% (44/1 402) vs. 1.07% (19/1 770), RR=3.47, 95%CI: 2.01-5.97, P 0.05 for both). Conclusions Combination of anticoagulants and SAPT or DAPT in ACS patients may all increase the risk of clinical major bleeding, but combination of SAPT and NOAC may reduce the risk of MACE, and should be used after weighing. For patients who must be treated with triple antithrombotic therapy, DAPT combined with NOAC can be chosen and warfarin should be avoided. Key words: Anticoagulants; Administration, oral; Acute coronary syndrome; Hemorrhage; Cardiovascular diseases; Meta-analysis; Randomized controlled trial