Safety of an abbreviated duration of dual antiplatelet therapy (≤6 months) following second-generation drug-eluting stents for coronary artery disease: A systematic review and meta-analysis of randomized trials

Abstract

Background: Dual antiplatelet therapy (DAPT) is recommended for ≥12 months following coronary drug-eluting stents (DES) to reduce risk of major adverse ischemic events. Randomized trials suggest an abbreviated DAPT duration (≤6 months) is adequately protective. However, these trials are individually underpowered to detect differences in rare but serious events such as stent thrombosis (ST).

Objectives: We performed a meta-analysis of published randomized trials to define the impact of abbreviated DAPT (≤6 months) on death, myocardial infarction (MI), stent thrombosis (ST), and bleeding complications compared to standard-duration DAPT (≥12 months).

Methods: Seven randomized controlled trials comparing abbreviated vs. standard DAPT regimens following DES use were identified by two independent investigators. Study characteristics were reviewed and clinical endpoint data were abstracted and analyzed in aggregate using fixed and random-effects models.

Results: The seven trials included 15,874 randomized patients. Second-generation DES were used in most patients. Compared to standard-duration DAPT, abbreviated DAPT was not associated with an increase in mortality (OR 0.93; CI: 0.73 to 1.17; P = 0.52), MI (OR 1.14; CI: 0.89 to 1.45; P = 0.30) or ST (OR 1.25; CI: 0.81 to 1.93; P = 0.31). Abbreviated DAPT was associated with significantly fewer major bleeding complications (OR 0.52; CI: 0.34 to 0.82; P = 0.005). The results were consistent between fixed and random-effects models, with no heterogeneity. Sensitivity analyses adjusting for inclusion of bare metal stents, 1st generation DES and/or abbreviated DAPT regimens of 3 months resulted in similar conclusions.

Conclusions: In a meta-analysis of >15,000 patients primarily treated with second-generation DES, abbreviated-duration DAPT (≤6 months) was associated with a significant reduction in major bleeding complications with no evidence of a significant increase in risk of death, MI or ST. Accordingly, abbreviated DAPT should be strongly considered for patients receiving second generation DES.

Keywords: drug-eluting stents; dual antiplatelet therapy; meta-analysis; percutaneous coronary intervention.

Figure 1

Selection of trials for inclusion in meta-analysis.

Figure 2

Odds ratio for all-cause mortality (top) and cardiac mortality (bottom). Forest plots of unadjusted odds ratio (OR, with 95% CIs) for all-cause and cardiac mortality in patients receiving abbreviated- vs. standard-DAPT regimens. There was no significant difference in the odds of all-cause or cardiac mortality between the 2 groups (OR 0.93; CI: 0.73 to 1.17; P = 0.52 and OR 0.97; CI: 0.71 to 1.32; P = 0.83 respectively).

Figure 3

Odds ratio for stent thrombosis (ST). Forest plot of unadjusted odds ratio (OR, with 95% CIs) for definite or probable ST in patients receiving abbreviated- vs. standard-DAPT regimens. There was no significant difference in the odds of stent thrombosis between the 2 groups (OR 1.25; CI: 0.81 to 1.93; P = 0.31).

Figure 4

Odds ratio for major bleeding. Forest plot of unadjusted odds ratio (OR, with 95% CIs) for major bleeding in patients receiving abbreviated- vs. standard-DAPT regimens. There was a significant reduction in the estimated OR of major bleeding in patients treated with abbreviated DAPT (OR 0.52; CI: 0.34 to 0.82; P = 0.005).

Figure 5

Odds ratios and confidence intervals for major adverse outcomes according to the primary meta-analysis and the secondary analyses adjusting for important variations in study methodologies. Conclusions were consistent among all secondary analyses and similar to the primary analysis conclusions.