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Published on: February 26, 2013
Combination of antiplatelet and anticoagulant therapy, component network meta-analysis of randomized controlled
László Szapáry1, Dániel Tornyos1, Péter Kupó1
1Department of Interventional Cardiology, Heart Institute, Medical School, University of Pécs, Pécs, Hungary.
Background:
Despite numerous randomized clinical trials (RCT), data regarding the efficacy of antiplatelet and anticoagulant combinations are still conflicting. We aimed to analyze treatment options tested in various fields of cardiovascular prevention, regarding their efficacy and bleeding risk.
Methods:
Systematic searches of electronic databases were conducted until June 2022. A component network meta-analysis was performed in R. Risk estimates across trials were pooled using random-effects model selecting risk ratio (RR) with 95% confidence intervals (95% CIs) as summary statistics. The primary endpoint of interest was the rate of major cardiac adverse events (MACE). Major bleeding events were assessed as main safety endpoint. Secondary outcomes included cardiovascular- and overall mortality, myocardial infarction (MI), stent thrombosis, and stroke.
Results:
Fifteen studies randomizing 73,536 patients were identified. The MACE risk reflected heterogeneity among the anticoagulants with dabigatran and apixaban significantly reducing the risk of MACE (RR 0.56; 95% CI 0.39-0.80 and RR 0.75; 95% CI 0.58-0.98, respectively). Vitamin K antagonist (VKA), rivaroxaban, or edoxaban did not reduced of MACE while it was associated with a significant increase of bleeding risk (RR 1.66; 3.66, and 5.47, respectively). The direct anticoagulant (DOAC) dose reduction resulted in tendencies of fewer bleeding but higher MACE risk, while combination with aspirin was followed with increased risk for bleeding, however, remained non-significant in these cases.
Conclusion:
Our meta-analysis supports that the ischemic-bleeding balance is different among direct-acting oral anticoagulants (DOACs) while this is not significantly affected by the dose reduction approaches. Long-term aspirin treatment as part of the anticoagulant and dual antiplatelet regimen provides no ischemic benefit but may increase bleeding risk.
Systematic Review Registration:
[https://www.crd.york.ac.uk/prospero/], identifier [259703].
Insights
Direct-acting oral anticoagulants (DOACs) like dabigatran and apixaban reduce major adverse cardiac events (MACE) without increasing bleeding risk. Long-term aspirin with anticoagulants offers no ischemic benefit and may raise bleeding risk.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Conflicting data exist on antiplatelet and anticoagulant combinations for cardiovascular prevention.
- Efficacy and bleeding risks of various treatment options require further analysis.
Approach:
- A systematic literature search identified 15 randomized clinical trials (RCTs) involving 73,536 patients.
- A network meta-analysis pooled risk ratios (RR) with 95% confidence intervals (95% CIs) for major adverse cardiac events (MACE) and major bleeding.
Key Points:
- Dabigatran and apixaban significantly reduced MACE risk (RR 0.56; 0.75).
- Vitamin K antagonists, rivaroxaban, and edoxaban did not reduce MACE but increased bleeding risk.
- DOAC dose reduction showed trends toward less bleeding but higher MACE; aspirin combination increased bleeding risk.
Conclusions:
- The ischemic-bleeding balance varies among DOACs, unaffected by dose reduction.
- Long-term aspirin in dual regimens provides no ischemic benefit and may increase bleeding risk.
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