Coronary Artery Disease
Meta-Analysis of the Safety and Efficacy of the Oral Anticoagulant Agents (Apixaban, Rivaroxaban, Dabigatran) in Patients With Acute Coronary Syndrome

https://doi.org/10.1016/j.amjcard.2017.10.035Get rights and content

The significance of adding new oral anticoagulants (NOACs) to antiplatelet therapy in patients with acute coronary syndrome (ACS) is unclear. We conducted a meta-analysis to assess the safety and efficacy of adding NOACs (apixaban, rivaroxaban, and dabigatran) to single antiplatelet agent (SAP) or dual antiplatelet therapy (DAPT) in patients with ACS. Seven randomized controlled trials were selected using PubMed or MEDLINE, Scopus, and Cochrane library (inception to August 2017). The summary measure was random effects hazard ratio (HR) with 95% confidence interval (CI). The primary safety outcome was clinically significant bleeding. The secondary efficacy outcome was major adverse cardiovascular events (MACE; composite of myocardial infarction, stroke, and all-cause mortality). In 31,574 patients, addition of NOAC to SAP did not increase the risk of clinically significant bleeding (HR 0.82, 95% CI 0.56 to 1.20, p = 0.31); however, the risk of clinically significant bleeding was significantly increased with NOAC plus DAPT (HR 2.24, 95% CI 1.75 to 2.87, p < 0.001). NOACs had no statistically beneficial effect on MACE when used with SAP (HR 0.82, 95% CI 0.66 to 1.04, p = 0.10); however, a modest reduction in MACE was observed when NOACs were combined with DAPT (HR 0.86, 95% CI 0.78 to 0.93, p < 0.001). In conclusion, in patients with ACS, the addition of NOAC to DAPT resulted in increased risk of clinically significant bleeding, whereas only a modest reduction in MACE was achieved. The addition of NOACs to SAP did not result in significant reduction of MACE or increase in clinically significant bleeding.

Section snippets

Methods

The present meta-analysis is conducted according to Cochrane Collaboration guidelines and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses report.11, 12 The following inclusion criteria were set: (1) randomized clinical trials (phase II and III) investigating commonly prescribed NOACs (apixaban, rivaroxaban, and dabigatran) in patients with ACS, (2) included studies had to report outcomes of interest (see below) in adult population (aged ≥18 years), and

Results

In the selected trials, APPRAISE, APPRAISE-2, 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 trial 46), ATLAS ACS-TIMI 51, and REDEEM (Dabigatran vs placebo in patients with ACS on DAPT: a randomized, double-blind, phase II trial) investigated the effects of NOACs in patients with recent ACS, whereas both PIONEER AF and RE DUAL PCI

Discussion

The cardiologists should continue to engage in efforts to encounter the risk of recurrent ischemia in patients with ACS. The professional guidelines are clear about the parenteral anticoagulants during the acute care of ACS; however, their role is not clearly defined after hospital discharge. In the recent times, there is an ongoing effort to assess the effects of NOACs in this regard. We have combined all the phase II and III clinical trials of commonly used NOACs, which have investigated

Disclosures

Dr. Kaluski is a speaker and consultant for Bristol-Myers Squibb, Pfizer, Janssen, and Daiichi-Saknyo. The authors have not received any funding for this project.

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