Background: Whether high-dose clopidogrel may improve early clinical outcome has been debated. We compared the efficacy and safety of high-dose (600mg) vs. moderate-dose (300mg) clopidogrel loading in patients with Non-ST-elevation acute coronary syndrome [ACS] or stable angina who receive drug-eluting stents, and clarify treatment effects in several clinical and anatomic subgroups.
Methods: Among 2645 patients enrolled in the ZEST trial, we evaluated 1612 patients with eligible data regarding clopidogrel loading dose and who not on chronic clopidogrel therapy: 300mg (N=1399) or 600mg (N=213) loading. Primary outcome was an incidence of major adverse cardiac event (MACE: death, myocardial infarction [MI], target-lesion revascularization) at 30 day. We evaluated treatment effect in several subgroups according to age, sex, and the presence or absence of diabetes, ACS, acute MI, multivessel disease, long lesion, or small vessel.
Result: At 30 days, MACE occurred 5.8% in 300mg group and 4.2% in 600mg group (p=0.35). After multivariable-adjustment, there was no difference of risk of MACE between the groups (odd ratio 0.79, 95% CI 0.39-1.61, p=0.51). This trend was consistent in several subgroups (figure). Additionally, the incidence of major and minor bleeding was similar in 300mg and 600mg groups (major: 0.3% vs. 0.0%, p=1.0 and minor: 0.7% vs. 0.0%, p=0.38).
Conclusion: In patient with Non-ST-elevation ACS and stable angina, high-dose (600mg) clopiodgrel loading did not significantly reduce early major cardiac event compared with moderate-dose (300mg). Our findings should be refuted or confirmed in large randomized trial.