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Meta-Analysis
. 2018 Mar 1;3(3):234-241.
doi: 10.1001/jamacardio.2017.5306.

Direct Oral Anticoagulants in Addition to Antiplatelet Therapy for Secondary Prevention After Acute Coronary Syndromes: A Systematic Review and Meta-analysis

Mauro Chiarito  1   2 , Davide Cao  1   2 , Francesco Cannata  1   2 , Cosmo Godino  3 , Corrado Lodigiani  2 , Giuseppe Ferrante  1   2 , Renato D Lopes  4 , John H Alexander  4 , Bernhard Reimers  1   2 , Gianluigi Condorelli  1   2 , Giulio G Stefanini  1   2
Affiliations
Meta-Analysis

Direct Oral Anticoagulants in Addition to Antiplatelet Therapy for Secondary Prevention After Acute Coronary Syndromes: A Systematic Review and Meta-analysis

Mauro Chiarito et al. JAMA Cardiol. .

Erratum in

  • Errors in Figure 3 and Affiliations.
    [No authors listed] [No authors listed] JAMA Cardiol. 2018 May 1;3(5):445. doi: 10.1001/jamacardio.2018.0643. JAMA Cardiol. 2018. PMID: 29590285 Free PMC article. No abstract available.

Abstract

Importance: Patients with acute coronary syndrome (ACS) remain at high risk for experiencing recurrent ischemic events. Direct oral anticoagulants (DOAC) have been proposed for secondary prevention after ACS.

Objective: To evaluate the safety and efficacy of DOAC in addition to antiplatelet therapy (APT) after ACS, focusing on treatment effects stratified by baseline clinical presentation (non-ST-segment elevation ACS [NSTE-ACS] vs ST-segment elevation myocardial infarction [STEMI]).

Data sources: PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched from inception to March 1, 2017.

Study selection: Randomized clinical trials on DOAC after ACS were evaluated for inclusion. Overall, 473 studies were screened, 19 clinical trials were assessed as potentially eligible, and 6 were included in the meta-analysis.

Data extraction and synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used to abstract data and assess quality and validity. The risk of bias tool, version 2.0 (Cochrane) was used for risk of bias assessment. Data were pooled using random-effects models.

Main outcomes and measures: The prespecified primary efficacy end point was the composite of cardiovascular death, myocardial infarction, and stroke. The prespecified primary safety end point was major bleeding.

Results: Six trials that included 29 667 patients were identified (14 580 patients [49.1%] with STEMI and 15 036 [50.7%] with NSTE-ACS). The primary efficacy end point risk was significantly lower in patients who were treated with DOAC as compared with APT alone (odds ratio [OR], 0.85; 95% CI, 0.77-0.93; P < .001). This benefit was pronounced in patients with STEMI (OR, 0.76; 95% CI, 0.66-0.88; P < .001), while no significant treatment effect was observed in patients with NSTE-ACS (OR, 0.92; 95% CI, 0.78-1.09; P = .36; P for interaction = .09). With respect to safety, DOACs were associated with a higher risk of major bleeding as compared with APT alone (OR, 3.17; 95% CI, 2.27-4.42; P < .001), with consistent results in patients with STEMI (OR, 3.45; 95% CI, 1.95-6.09; P < .001) and NSTE-ACS (OR, 2.19; 95% CI, 1.38-3.48; P < .001; P for interaction = .23).

Conclusions and relevance: To our knowledge, these findings are the first evidence to support differential treatment effects of DOAC in addition to APT according to ACS baseline clinical presentation. In patients with NSTE-ACS, the risk-benefit profile of DOAC appears unfavorable. Conversely, DOAC in addition to APT might represent an attractive option for patients with STEMI.

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Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Stefanini reports receiving a research grant from Boston Scientific and speaker/consulting fees from B. Braun, Biosensors, Boston Scientific, and Edwards Lifesciences. Dr Alexander reports receiving grants from Bristol-Myers Squibb, Boehringer Ingelheim, the US Food and Drug Administration, the National Institutes of Health, Tenax Therapeutics, and Sanofi; personal fees from Pfizer, Cempra, Merck, Novo Nordisk, Portold Pharmaceuticals, the Veterans Affairs Cooperative Studies Program, VasoPrep Surgical, and Zafgen; and grants and personal fees from CryoLife and CSL Behring. Dr Lopes reports receiving personal fees from Bayer, Boehringer Ingleheim, Daiichi Sankyo, Merck, and Portola and grants and personal fees from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, and Pfizer. No other disclosures are reported.

Figures

Figure 1.
Figure 1.. Flowchart of the Study Selection Process
DOAC indicates direct oral anticoagulant; PCI, percutaneous coronary intervention.
Figure 2.
Figure 2.. Risk of the Primary Efficacy End Point and the Primary Safety End Point With Direct Oral Anticoagulant (DOAC) in Addition to Antiplatelet Therapy (APT) as Compared With APT Alone, Overall and Stratified by Acute Coronary Syndrome Type
A, Efficacy end point. B, Safety end point. Only studies that reported outcomes stratified for the index event are included. Weights are from a random-effects analysis. APPRAISE indicates Apixaban for Prevention of Acute Ischemic Events; ATLAS ACS TIMI 46, Rivaroxaban versus Placebo in Patients With Acute Coronary Syndromes; CV death, cardiovascular death; MI, myocardial infarction; NSTE-ACS, non–ST-segment elevation myocardial infarction; OR, odds ratio; STEMI, ST-segment elevation myocardial infarction.
Figure 3.
Figure 3.. Number Needed to Prevent an Ischemic Event and Cause a Bleeding Event
Overall and in patients with ST-segment elevation myocardial infarction (STEMI) and non–ST-segment elevation acute coronary syndromes (NSTE-ACS).
See this image and copyright information in PMC

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