New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis
Open accessAbstract
BACKGROUND: Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting. METHODS AND RESULTS: All seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7-14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59-0.84], but increased clinically significant bleeding (HR: 1.79; 1.54-2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80-0.95), but more than doubled the bleeding (HR: 2.34; 2.06-2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies. CONCLUSION: In patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with dual antiplatelet therapy.
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In patients without AF, the addition of a NOAC to antiplatelet therapy reduced recurrent ischaemic events only marginally.
“The addition of a NOAC increased the bleeding risk by 79-134%, while 1504 reducing recurrent ischaemic events only marginally in patients without AF.”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [519]
In patients without AF, the addition of a NOAC to antiplatelet therapy increased the bleeding risk by 79-134%.
“The addition of a NOAC increased the bleeding risk by 79-134%, while 1504 reducing recurrent ischaemic events only marginally in patients without AF.”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [519]
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2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
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- Authors
- Oldgren, J., Wallentin, L., Alexander, J. H., James, S., Jonelid, B., Steg, G., & Sundstrom, J.
- Affiliations
- Uppsala University (SE)
- Duke Medical Center (US)
- Corresponding author
- Oldgren, J.
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-03-06
- Volume
- 34
- Issue
- 22
- Pages
- 1670-1680
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- PMC
- PMC3675388
- OpenAlex
- W2029400346
- Cited by
- 198
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 8 · 2021: 9 · 2020: 5 · 2019: 8 · 2018: 23 · 2017: 28 · 2016: 23 · 2015: 26 · 2014: 35 · 2013: 21
- FWCI
- 5.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- European Heart Journal (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- CSL Behring
- Ablynx
- Amarin Corporation
- Medicines Company
- Regado Biosciences
- Institut National de la Santé et de la Recherche Médicale (U-698)
- Daiichi-Sankyo
- Eisai
- Hjärt-Lungfonden (20041151, grant 20041151)
- Vetenskapsrådet
- Astellas Pharma
- Servier
- National Institutes of Health
- School of Medicine, New York University
- Janssen Pharmaceuticals
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- direct oral anticoagulants, acute coronary syndrome, antiplatelet therapy, aspirin, clopidogrel, direct thrombin inhibitors, factor Xa inhibitors, apixaban, dabigatran, rivaroxaban, ximelagatran, major adverse cardiovascular events, bleeding risk, combination therapy
- MeSH terms
- Administration, Oral, Aged, Anticoagulants, Drug Combinations, Female, Hemorrhage, Humans, Male, Middle Aged, Platelet Aggregation Inhibitors, Randomized Controlled Trials as Topic, Treatment Outcome, Clinical Trials, Phase I as Topic, Clinical Trials, Phase II as Topic, Acute Coronary Syndrome
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