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Antithrombotic agents for secondary prevention after acute coronary syndromes: A systematic review and network
Alexander C Fanaroff1, Vic Hasselblad2, Matthew T Roe1
1Division of Cardiology, Duke University, Durham, NC, USA; Duke Clinical Research Institute, Duke University, Durham, NC, USA.
Insights
Few antithrombotic medication combinations significantly reduced mortality compared to aspirin monotherapy after acute coronary syndrome (ACS). Combination therapy with aspirin plus ticagrelor showed lower cardiovascular mortality, while triple therapy reduced all-cause mortality but increased bleeding risk.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Nine oral antithrombotic medications are available for secondary prevention post-acute coronary syndrome (ACS).
- Limited direct comparisons exist between medication combinations, and studies use varied comparator regimens.
Purpose of the Study:
- To systematically review and network meta-analyze randomized controlled trials (RCTs) of oral antithrombotic therapies.
- To compare co-primary outcomes of all-cause and cardiovascular mortality against placebo and aspirin monotherapy in patients with ACS or myocardial infarction (MI).
Main Methods:
- Systematic review and network meta-analysis of 47 RCTs involving 196,057 patients.
- Evaluated oral antithrombotic therapies for secondary prevention in ACS or prior MI.
- Compared outcomes against imputed placebo and aspirin monotherapy.
Main Results:
- Nearly all regimens reduced mortality versus placebo.
- Aspirin plus ticagrelor showed lower cardiovascular mortality than aspirin monotherapy (OR 0.80).
- Triple therapy (aspirin, clopidogrel, low-dose rivaroxaban) reduced all-cause mortality (OR 0.67) but significantly increased bleeding risk.
Conclusions:
- Few antithrombotic combinations demonstrated mortality reduction versus aspirin monotherapy.
- Balancing ischemic event reduction and bleeding risk is challenging with current composite endpoints.
- Future research should focus on fewer antithrombotic agents in combination trials.
Background:
Nine oral antithrombotic medications currently available in the United States and Europe have been studied in clinical trials for secondary prevention of cardiac events following acute coronary syndrome (ACS). Few combinations of these medications have been directly compared, and studies have used multiple different comparator regimens.
Methods:
We performed a systematic review and network meta-analysis of randomized controlled trials evaluating one or more available oral antithrombotic therapies in patients with ACS or prior myocardial infarction (MI). Co-primary outcomes were all-cause and cardiovascular mortality compared with imputed placebo and aspirin monotherapy.
Results:
Forty-seven studies (196,057 subjects) met inclusion criteria and were included in the systematic review. Almost all studies tested either aspirin monotherapy compared with placebo or a combination of antithrombotic agents that included aspirin. Nearly all regimens reduced all-cause and cardiovascular mortality compared with imputed placebo. However, compared with imputed aspirin monotherapy, only combination therapy with aspirin plus ticagrelor was associated with lower cardiovascular mortality (OR 0.80, 95% CI 0.68-0.93), and triple therapy with aspirin, clopidogrel, and very low dose rivaroxaban was associated with lower all-cause mortality (OR 0.67, 95% CI 0.49-0.90). Major bleeding was increased 45-95% with dual antithrombotic therapy, and 2-6-fold with triple therapy.
Conclusion:
Few combinations of antithrombotic therapy were associated with a reduction in mortality compared with aspirin monotherapy, highlighting the difficulty in clinical interpretation of composite ischemic endpoints. Future studies may need to focus on limiting the number of antithrombotic therapies tested in combination to best balance ischemic event reduction and bleeding.
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