Abstract
Objectives To investigate outcomes with selective, clopidogrel-based therapies versus conventional
treatment in patients undergoing percutaneous coronary intervention (PCI), especially
for acute coronary syndrome.
Background Safety and efficacy of alternative, selective, clopidogrel-based therapies after
PCI are not robustly established.
Methods We performed a study-level meta-analysis on six randomized trials investigating selective
clopidogrel-based therapies (three on unguided de-escalation, N = 3,473; three on guided clopidogrel therapy, N = 7,533). Control groups received ticagrelor or prasugrel treatment. Main endpoints
were major bleeding, any bleeding, major adverse cardiovascular events (MACE), and
net clinical endpoint.
Results The incidence of major bleeding and MACE was similar in the selective, clopidogrel-based
therapy versus the conventional treatment arm (odds ratio [OR]: 0.72, 95% confidence
interval [CI]: 0.51–1.01, p = 0.06; OR: 0.93, 0.72–1.20, p = 0.58; respectively). The rates of any bleeding were lower in the selective, clopidogrel-based
therapy versus conventional treatment group (OR: 0.57, 95% CI: 0.40–0.80, p = 0.001); this greater safety was significant for unguided de-escalation (OR: 0.43,
95% CI: 0.32–0.58, p = 0.00001) and nonsignificant for guided clopidogrel therapy (OR: 0.72, 95% CI: 0.51–1.02,
p = 0.07; p for interaction: 0.03). The incidence of the net clinical endpoint was fewer in the
selective, clopidogrel-based therapy versus the conventional treatment arm (OR: 0.59,
95% CI: 0.41–0.85, p = 0.004); this benefit was significant for unguided de-escalation (OR: 0.50, 95%
CI: 0.39–0.64, p < 0.00001) and nonsignificant for guided clopidogrel therapy (OR 0.85, 95% CI: 0.62–1.16,
p = 0.30; p for interaction: 0.01).
Conclusion As compared with prasugrel/ticagrelor treatment, alternative, selective, clopidogrel-based
approaches provide a similar protection from cardiovascular events, reduce the risk
of any bleeding, and are associated with a greater net benefit. These beneficial effects
were prevalent with unguided de-escalation to clopidogrel.
Keywords
acute coronary syndrome - percutaneous coronary intervention - de-escalation - guided
clopidogrel therapy - MACE
