Key result
Shorter DAPT after DES cuts bleeding-related death ~35% vs prolonged therapy, reducing overall mortality.
Why the study?
The mechanistic underpinnings of the potential association between prolonged dual-antiplatelet therapy (DAPT) and increased mortality after drug-eluting stent implantation remained unclear.
Does shorter dual-antiplatelet therapy duration reduce all-cause and bleeding-related mortality compared to longer dual-antiplatelet therapy in patients undergoing drug-eluting stent implantation?
Meta-Analysis
Does shorter dual-antiplatelet therapy duration reduce all-cause and bleeding-related mortality compared to longer dual-antiplatelet therapy in patients undergoing drug-eluting stent implantation?
Shorter DAPT duration after drug-eluting stent placement reduces all-cause mortality primarily by decreasing bleeding-related deaths, as post-stenting bleeding strongly predicts 1-year mortality.
May heighten caution on DAPT prolongation after stenting; hypothesis-generating and leaves optimal duration open for research.
Background Although some randomized controlled trials (RCTs) and meta-analyses have suggested that prolonged dual-antiplatelet therapy (DAPT) may be associated with increased mortality, the mechanistic underpinnings of this association remain unclear. Objectives The aim of this study was to analyze the associations among bleeding, mortality, and DAPT duration after drug-eluting stent implantation in a meta-analysis of RCTs. Methods RCTs comparing different DAPT durations after drug-eluting stent placement were sought through the MEDLINE, Embase, and Cochrane databases and the proceedings of international meetings. Deaths were considered possibly bleeding related if occurring within 1 year of the episodes of bleeding. Primary analysis was by intention-to-treat. Secondary analysis was performed in a modified intention-to-treat population in which events occurring when all patients were on DAPT were excluded. Results Individual patient data were obtained for 6 RCTs, and aggregate data were available for 12 RCTs. Patients with bleeding had significantly higher rates of mortality compared with those without, and in a time-adjusted multivariate analysis, bleeding was an independent predictor of mortality occurring within 1 year of the bleeding episode (hazard ratio: 6.93; 95% confidence interval: 4.53 to 10.60; p < 0.0001). Shorter DAPT was associated with lower rates of all-cause death compared with longer DAPT (hazard ratio: 0.85; 95% confidence interval: 0.73 to 1.00; p = 0.05), which was driven by lower rates of bleeding-related deaths with shorter DAPT compared with prolonged DAPT (hazard ratio: 0.65; 95% confidence interval: 0.43 to 0.99; p = 0.04). Mortality unrelated to bleeding was comparable between the 2 groups. Similar results were apparent in the modified intention-to-treat population. Conclusions Bleeding was strongly associated with the occurrence of mortality within 1 year after the bleeding event. Shorter compared with longer DAPT was associated with lower risk for bleeding-related death, a finding that may underlie the lower all-cause mortality with shorter DAPT in the RCTs of different DAPT durations after DES.
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Palmerini et al. (2017) conducted a meta-analysis in Coronary artery disease treated with drug-eluting stent implantation. Shorter dual-antiplatelet therapy (DAPT) vs. Longer/prolonged dual-antiplatelet therapy (DAPT) was evaluated on Bleeding-related death (death occurring within 1 year of a bleeding episode) (HR 0.65, 95% CI 0.43-0.99, p=0.04). Shorter DAPT after DES reduced bleeding-related death vs prolonged DAPT (HR 0.65; 95% CI 0.43-0.99; p=0.04), driving lower all-cause mortality (HR 0.85; 95% CI 0.73-1.00; p=0.05).
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