| Summary: | Background Recent guidelines on dual antiplatelet therapy (DAPT) duration after percutaneous coronary intervention (PCI) balance the subsequent risks of major bleeding with ischemic events. Although generally favoring shorter DAPT duration with second‐generation drug‐eluting stents, the effects on long‐term outcomes in the wider population are uncertain. Methods and Results We tracked all patients having PCI with second‐generation drug‐eluting stents in the Veterans Affairs Healthcare System between 2006 and 2016 for death, myocardial infarction, stroke, and major bleeding up to 13 years. We compared these outcomes with 4 DAPT durations of 1 to 5, 6 to 9, 10 to 12, and 13 to 18 months after the index PCI using hazard ratios (HRs) and 95% CIs from Cox proportional hazards models adjusted by inverse probability weighting. A total of 40 882 subjects with PCI were followed up for a median of 4.3 (25%–75%: 2.4–6.5) years. DAPT discontinuation was rare early after PCI (5.8% at 1–5 months and 6.3% at 6–9 months) but increased (19% and 44%) >9 months. The risk of cardiovascular and noncardiovascular death was higher (HR, 2.03–3.41) with DAPT discontinuation <9 months, likely reflecting premature cessation from factors related to early death. DAPT discontinuation after 9 months following PCI was associated with lower risks of death (HR, 0.93 [95% CI, 0.88–0.99]), cardiac death (HR, 0.79 [95% CI, 0.70–0.90]), myocardial infarction (HR, 0.75 [95% CI, 0.69–0.82]), and major bleeding (HR, 0.82 [95% CI, 0.74–0.91]). Results were similar with an index PCI for an acute coronary syndrome. Conclusions Stopping DAPT after 9 months is associated with lower long‐term risks of adverse ischemic and bleeding events and supports recent guidelines of shorter duration DAPT after PCI with second‐generation drug‐eluting stents.
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