Myocardial Infarction Risk after Discontinuation of Thienopyridine Therapy in the Randomized DAPT Study
Background—Thienopyridine plus aspirin beyond one year after coronary stenting (PCI) reduces myocardial infarction (MI) risk and increases bleeding risk compared with aspirin alone. The hazard associated with late thienopyridine discontinuation and risk factors for MI after discontinuation are poorly defined.
Methods—In the Dual Antiplatelet Therapy (DAPT) Study, after PCI and 12 months of thienopyridine (clopidogrel or prasugrel) plus aspirin, eligible patients remained on aspirin and were randomized to continued thienopyridine vs. placebo for 18 months. At 30 months, patients stopped study drug and were observed for 3 months. Cumulative incidence of MI was assessed over 3 months after randomization (months 12-15) and 3 months after study drug discontinuation (months 30-33). The MI hazard for each of these periods was assessed across randomized treatment arms and by DAPT Score values < or ≥2.
Results—Among the 11648 randomized patients, the monthly cumulative incidence of MI was lower with continued thienopyridine vs. placebo at 12-15 months (0.12% vs. 0.37%, p<0.001 in all patients; 0.13% vs. 0.27%, p=0.02, in patients not treated with paclitaxel-eluting stents, PES), and higher at 30-33 months (0.30% vs. 0.15%, p=0.013, in all patients; in patients without PES, 0.18% vs. 0.17%, p=0.91). The majority of MIs in both time periods (74% and 76%) were not related to stent thrombosis (ST). After multivariable adjustment, treatment arm independently predicted MI at months 12-15 (p<0.001) and 30-33 (p=0.011). During months 12-15, patients with DAPT Scores < or ≥2 both had lower rates of MI with continued thienopyridine (MI monthly incidence 0.16% vs. 0.51%, p<0.001, for scores ≥2; 0.08% vs. 0.24%, p=0.012, for scores<2, interaction p=0.064).
Conclusions—Discontinuing thienopyridine after either 12 or 30 months is associated with an early increase in MI risk, mainly unrelated to ST; the magnitude of risk is highest in the earlier time frame, and lower in patients not treated with PES. While higher DAPT Scores identify patients with greater absolute ischemic benefit (relative to bleeding harm) with continued thienopyridine therapy, discontinuation at 12 months increases MI hazard regardless of DAPT score group.
Clinical Trial Registration— https://clinicaltrials.gov Identifier: NCT00977938
- Received September 5, 2016.
- Revision received February 6, 2017.
- Accepted February 13, 2017.