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Direct Xa inhibitors in addition to antiplatelet therapy in acute coronary syndrome: meta-analysis of randomized trials

Villablanca, Pedro A.a; Holmes, David Jrc; Mohananey, Divyanshud; Briceno, David F.a; Núñez Gil, Ivan J.g; Kargoli, Faraja; Gupta, Tanusha; Kizer, Jorge R.a,b; Bortnick, Anna E.a; Wiley, Josea; Menegus, Mark A.a; Pyo, Roberta; García, Marioa; Ramakrishna, Harishe; Mookadam, Faroukf

doi: 10.1097/MCA.0000000000000485
Original Research

Objective We carried out a meta-analysis summarizing the efficacy and safety of direct factor Xa inhibitor (DXI) in patients receiving guideline-based antiplatelet therapy (GBAT) after an acute coronary syndrome.

Background Randomized-controlled trials have shown that the addition of a DXI to GBAT after acute coronary syndrome can reduce ischemic events, the trade-off being an increase in major bleeding complications.

Methods PubMed, Central, Embase, The Cochrane Register, Google Scholar databases, and the scientific session abstracts were searched for eligible randomized trials from 1 January 1990 through 31 December 2016.

Results Nine randomized-controlled trials were included in this meta-analysis enrolling a total of 45651 patients. There was a significant reduction in major adverse cardiovascular events with DXIs/GBAT compared with GBAT alone [odds ratio (OR): 0.88; 95% confidence interval (CI): 0.82–0.94, number needed to treat=52]. There were also significant reductions in two individual components of major adverse cardiovascular events: myocardial infarction (OR: 0.89; 95% CI: 0.81–0.98) and stent thrombosis (OR: 0.73; 95% CI: 0.59–0.90), favoring the DXI/GBAT group. There was an increased risk of major bleeding (OR: 2.51; 95% CI: 1.82–3.46) and intracranial hemorrhage (OR: 3.47; 95% CI: 1.76–6.86) compared with GBAT.

Conclusion In acute coronary syndromes, the addition of a DXI to GBAT results in a significant reduction of major adverse cardiovascular events, myocardial infarction, and stent thrombosis, offset by an increased risk of bleeding.

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aDepartment of Medicine, Division of Cardiovascular Diseases, Montefiore Medical Center

bDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, New York

cDepartment of Medicine, Cardiovascular Division, Mayo Clinic College of Medicine, Rochester, Minnesota

dDepartment of Internal Medicine, Cleveland Clinic, Cleveland, Ohio

eDepartment of Anesthesiology and Perioperative Medicine, Division of Cardiovascular and Thoracic Anesthesiology

fDepartment of Medicine, Cardiovascular Division, Mayo Clinic College of Medicine, Scottsdale, Arizona, USA

gDepartment of Medicine, Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain

Correspondence to Pedro A. Villablanca, MD, MSc, Division of Cardiovascular Diseases, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street Bronx, New York, NY 10467, USA Tel: +1 773 456 6609; fax: +1 718 920 6798;e-mails:,

Received February 9, 2017

Received in revised form February 23, 2017

Accepted February 25, 2017

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