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      Triple Therapy Versus Dual Antiplatelet Therapy for Patients with 
Atrial Fibrillation and Acute Coronary Syndromes: A Systematic 
Literature Review

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          Abstract

          Background:

          Patients with acute coronary syndromes (ACS) and a history of atrial fibril-lation (AF) have indications for both dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC). Triple therapy (TT), the combination of DAPT and OAC, is recommended in guidelines. We examined studies comparing clinical outcomes on DAPT versus TT for patients with AF and ACS.

          Methods:

          We searched Medline, Medline pending, EMBASE and Evidence-Based Medicine Re-views databases for studies published between January 2000 to December 2016 in AF patients with ACS that compared DAPT and TT that reported ischaemic and/or bleeding outcomes. Studies that were not purely an AF population were excluded.

          Results:

          Ten studies were included in the review, all of which were observational, 8 of which were retrospective. None of the studies detailed the specifics of treatment allocation. All but one were of AF patients with a mix of stable coronary disease and ACS patients. TT was associated with in-creased bleeding when compared to DAPT, with adjusted odds ratios ranging from 1.25 to 6.84. While the largest study reported a reduction in stroke associated with TT (odds ratio 0.67), two other studies reported non-significant increases in stroke with TT. Variable composite ischaemic endpoints were reported, none showing a statistical significant difference between DAPT and TT.

          Conclusion:

          In patients with ACS and AF, TT is likely to be associated with increased risk of bleed-ing, without a clear reduction in ischaemic endpoints. The quality of the evidence to support current guidelines for this patient group was generally poor.

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          Most cited references33

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          2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.

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            Predictors of hospital mortality in the global registry of acute coronary events.

            Management of acute coronary syndromes (ACS) should be guided by an estimate of patient risk. To develop a simple model to assess the risk for in-hospital mortality for the entire spectrum of ACS treated in general clinical practice. A multivariable logistic regression model was developed using 11 389 patients (including 509 in-hospital deaths) with ACS with and without ST-segment elevation enrolled in the Global Registry of Acute Coronary Events (GRACE) from April 1, 1999, through March 31, 2001. Validation data sets included a subsequent cohort of 3972 patients enrolled in GRACE and 12 142 in the Global Use of Strategies to Open Occluded Coronary Arteries IIb (GUSTO-IIb) trial. The following 8 independent risk factors accounted for 89.9% of the prognostic information: age (odds ratio [OR], 1.7 per 10 years), Killip class (OR, 2.0 per class), systolic blood pressure (OR, 1.4 per 20-mm Hg decrease), ST-segment deviation (OR, 2.4), cardiac arrest during presentation (OR, 4.3), serum creatinine level (OR, 1.2 per 1-mg/dL [88.4- micro mol/L] increase), positive initial cardiac enzyme findings (OR, 1.6), and heart rate (OR, 1.3 per 30-beat/min increase). The discrimination ability of the simplified model was excellent with c statistics of 0.83 in the derived database, 0.84 in the confirmation GRACE data set, and 0.79 in the GUSTO-IIb database. Across the entire spectrum of ACS and in general clinical practice, this model provides excellent ability to assess the risk for death and can be used as a simple nomogram to estimate risk in individual patients.
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              Rivaroxaban in patients with a recent acute coronary syndrome.

              Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Since factor Xa plays a central role in thrombosis, the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome. In this double-blind, placebo-controlled trial, we randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. The primary efficacy end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban significantly reduced the primary efficacy end point, as compared with placebo, with respective rates of 8.9% and 10.7% (hazard ratio in the rivaroxaban group, 0.84; 95% confidence interval [CI], 0.74 to 0.96; P=0.008), with significant improvement for both the twice-daily 2.5-mg dose (9.1% vs. 10.7%, P=0.02) and the twice-daily 5-mg dose (8.8% vs. 10.7%, P=0.03). The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes (2.7% vs. 4.1%, P=0.002) and from any cause (2.9% vs. 4.5%, P=0.002), a survival benefit that was not seen with the twice-daily 5-mg dose. As compared with placebo, rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting (2.1% vs. 0.6%, P<0.001) and intracranial hemorrhage (0.6% vs. 0.2%, P=0.009), without a significant increase in fatal bleeding (0.3% vs. 0.2%, P=0.66) or other adverse events. The twice-daily 2.5-mg dose resulted in fewer fatal bleeding events than the twice-daily 5-mg dose (0.1% vs. 0.4%, P=0.04). In patients with a recent acute coronary syndrome, rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding. (Funded by Johnson & Johnson and Bayer Healthcare; ATLAS ACS 2-TIMI 51 ClinicalTrials.gov number, NCT00809965.).
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                Author and article information

                Journal
                Curr Cardiol Rev
                Curr Cardiol Rev
                CCR
                Current Cardiology Reviews
                Bentham Science Publishers
                1573-403X
                1875-6557
                November 2017
                November 2017
                : 13
                : 4
                : 325-333
                Affiliations
                [1 ]Department of Surgery & Anaesthesia, University of Otago , Wellington, , New Zealand;
                [2 ] Wellington Cardiovascular Research Group , Wellington, , New Zealand;
                [3 ]Department of Cardiology, Wellington Hospital , Wellington, , New Zealand
                Author notes
                [* ]Address correspondence to this author at the University of Otago, Wellington. 23A Mein St, Newtown, Wellington, New Zealand, 6242.; Tel/Fax: 04 3855541; E-mail: aimee.fake@ 123456postgrad.otago.ac.nz
                Article
                CCR-13-325
                10.2174/1573403X13666170927121808
                5730966
                28969538
                0c38aa32-9476-44c7-9965-d8ac6cbef3e4
                © 2017 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 17 July 2017
                : 12 September 2017
                : 20 September 2017
                Categories
                Article

                Cardiovascular Medicine
                atrial fibrillation,acute coronary syndrome,triple therapy,dual antiplatelet therapy,systematic literature review

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