Related Experiment Video
Updated: May 18, 2026
The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation
Published on: February 28, 2012
Coronary and mortality risk of novel oral antithrombotic agents: a meta-analysis of large randomised trials
1Mak Heart Clinic, 6 Napier Road, #08-13, Singapore, Singapore, 258499.
Insights
Novel antithrombotic agents like dabigatran showed increased myocardial infarction risk, while rivaroxaban and apixaban demonstrated lower coronary event risk. All-cause mortality was reduced across these anticoagulants.
Area of Science:
- Cardiology
- Pharmacology
- Thrombosis Research
Background:
- Oral direct thrombin and anti-Xa inhibitors are effective for venous thromboembolism and atrial fibrillation.
- Recent data suggest dabigatran may increase myocardial infarction (MI) risk.
- Coronary risk associated with other novel oral anticoagulants remains unclear.
Purpose of the Study:
- To determine and compare the coronary risk among four novel oral antithrombotic agents: ximelagatran, dabigatran, rivaroxaban, and apixaban.
- Evaluate the impact of these agents on myocardial infarction or acute coronary syndrome (MI/ACS), major bleeding, and all-cause mortality.
Main Methods:
- A mixed-treatment comparison meta-analysis was conducted.
- Data were sourced from 28 randomized controlled trials (RCTs) including 138,948 participants, identified through PubMed and scientific meetings.
- A random-effects model was employed to assess outcomes.
Main Results:
- Dabigatran was associated with a significantly higher risk of MI/ACS (OR 1.30), while rivaroxaban showed a significantly lower risk (OR 0.78).
- Ximelagatran indicated a non-significant increase in MI/ACS risk, whereas apixaban demonstrated a non-significant decrease.
- Major bleeding rates varied, but all agents were linked to lower all-cause mortality without significant heterogeneity.
Conclusions:
- The risk of coronary events is significantly elevated with dabigatran and not significantly with ximelagatran, but lower with anti-Xa inhibitors (rivaroxaban, apixaban).
- Novel oral anticoagulants, including direct thrombin and anti-Xa inhibitors, reduce all-cause mortality.
- These findings aid in selecting appropriate anticoagulants for specific patient populations.
Objective:
Oral direct thrombin and anti-Xa inhibitors have been shown to be efficacious in the prevention and treatment of venous thromboembolism, and prevention of embolic events in atrial fibrillation. Recent studies showed that dabigatran may be associated with increased rates of myocardial infarction (MI). Coronary risk for the other agents was unclear. The aim of the study is to determine the coronary risk among four novel antithrombotic agents.
Design:
Mixed treatment comparison meta-analysis.
Data Sources And Study Selection:
Randomised controlled trials (RCTs) on ximelagatran, dabigatran, rivaroxaban and apixaban were obtained from PubMed search (February 2012) and major scientific meeting in 2011. The random-effects model was used to evaluate the effect of these agents on MI or acute coronary syndrome (MI/ACS), major bleeding complication and all-cause mortality.
Results:
From 28 RCTs (n=138 948), the risk for MI/ACS was higher for dabigatran (OR 1.30; 95% CI 1.04 to 1.63; p=0.021) but lower for rivaroxaban (OR 0.78; 95% CI 0.69 to 0.89; p<0.001). Ximelagatran showed a higher risk for MI/ACS, which was not statistically significant, while apixaban demonstrated a non-significant lower likelihood. Among the RCTs for MI/ACS among the four agents, only those pertaining to ximelagatran showed heterogeneity. Major bleeding complication rates varied considerably among different agents. Importantly, these agents were associated with a lower all-cause mortality, without heterogeneity among the studies.
Conclusions:
The risk for coronary events was significantly higher for dabigatran but not significantly higher for ximelagatran. Conversely, this risk was lower among anti-Xa inhibitors. All-cause mortality was lower among those receiving novel antithrombotic agents. This information may be useful in selecting agents for specific subsets of patients requiring anticoagulation.
Related Concept Videos
01:18Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:27Coronary Artery Disease V: Interprofessional Care
01:26Coronary Artery Disease IV: Preventive Measures
01:25Antianginal Drugs: Calcium Channel Blockers and Ranolazine
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...