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

Abstract

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.

Association of Parenteral Anticoagulation Therapy With Outcomes in Non–ST‐Segment Elevation Acute Coronary Syndrome Patients Without Invasive Therapy: Findings from the Improving Care for Cardiovascular Disease in China (CCC) project

“…Additionally, in patients managed with antiplatelet agents, thrombin generation was significantly inhibited, and the inhibition was more pronounced in those managed with DAPT than in those managed with a single antiplatelet agent 23–25 . Furthermore, most studies have failed to find any beneficial effect of new oral anticoagulation agents among patients with NSTE‐ACS in which DAPT was routinely used 26–28 . These findings add to the evidence supporting the reevaluation of the role of anticoagulation therapy in contemporary practice.…”

A systematic review and Bayesian network meta‐analysis of risk of intracranial hemorrhage with direct oral anticoagulants

“…This is because in coronary artery disease patients, studies were designed to compare DOACs (with background antiplatelet therapy) with placebo, which had the potential of overestimating the bleeding tendency of DOACs. This aspect was validated in former meta‐analyses . Similarly, in two trials of NVAF after PCI , DOACs with single or dual antiplatelet therapy (DAPT) were compared with triple therapy (warfarin plus DAPT).…”

Non-vitamin K oral anticoagulants for coronary or peripheral artery disease: a systematic review and meta-analysis of mortality and major bleeding

“…american Heart association, european Society of Cardiology) against or towards the use of NoaCs in this patient population. Published meta-analyses compared NoaCs to vitamin K antagonist drugs in atrial fibrillation, [7][8][9] investigated NoaCs in addition to single or dual antiplatelet therapy in acute coronary syndrome (aCS), 10 focused on patients with ischemic heart disease 11 and explored the role of rivaroxaban in Cad. 12 results are contradictory and there is lack of a comprehensive meta-analysis on this important field.…”