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Mortality of Escalation and Modulation Antithrombotic Therapy in Coronary Artery Disease Patients: A Meta-analysis of Randomized Controlled TrialsFunding This project was funded by the National Key Research and Development Program of China (2017YFC0908800, to Yu-Jie Zhou), the Beijing Municipal Administration of Hospitals' Mission plan (SML20180601, to Yu-Jie Zhou), the China Postdoctoral Science Foundation (2021M692253, to Xiao-Teng Ma), the Beijing Postdoctoral Research Foundation (2021-ZZ-023, to Xiao-Teng Ma), the National Natural Science Foundation of China (81670391, to Zhi-Jian Wang).
Background The net clinical benefit of antithrombotic therapy (ATT) reflects the concomitant effects of bleeding and ischemic events.
Objectives We sought to assess the overall effect of the modulation or escalation of ATT on all-cause mortality as well as ischemic and bleeding events.
Methods We performed a meta-analysis of randomized controlled trials comparing escalation or modulation of ATT versus standard ATT in patients with coronary artery disease. A total of 32 studies with 160,659 subjects were enrolled in this analysis.
Results Neither escalation nor modulation of ATT has significant effect on all-cause mortality (escalation: relative risk [RR]: 0.94, 95% confidence interval [CI]: 0.85–1.04; modulation: RR: 0.90; 95% CI: 0.81–1.01). Compared with standard ATT therapy, escalation of ATT was associated with lower risk of myocardial infarction (MI; RR: 0.84, 95% CI: 0.76–0.94), but had a higher risk of major or minor bleeding (RR: 1.38, 95% CI: 1.15–1.66). Modulation of ATT was associated with a similar risk of MI (RR: 1.07, 95% CI: 0.96–1.19), but a reduced risk for major or minor bleeding (RR: 0.58, 95% CI: 0.51–0.66). Meta-regression combining both escalation and modulation studies found that the heterogeneity of all-cause mortality was mainly attributed to the heterogeneity of major or minor bleeding (adjusted R-squared = 100.00%, p = 0.004), but not to MI.
Conclusion Either escalation or modulation of ATT has little benefit in all-cause mortality. The variability of the treatment effects on all-cause mortality was mainly attributed to the variability of major or minor bleeding, but not to MI.
All authors contributed to study concept and design; Q.Y.S. and X.T.M. contributed to acquisition of data; Z.J.W. and Q.Y.S. did the statistical analysis; Q.Y.S. drafted the report; Z.J.W. contributed to critical revision of the manuscript for important intellectual content. All authors read and approved the final draft of the manuscript.
Ethics Committee Approval
This study was approved by the institutional review board of Beijing Anzhen Hospital, Capital Medical University.
Received: 03 March 2022
Accepted: 02 August 2022
Article published online:
07 November 2022
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