Elderly Patients with ACS: Clopidogrel or Reduced-Dose Prasugrel?

Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome (ACS), and display higher platelet reactivity under clopidogrel when compared to younger patients. A 5-mg dose of prasugrel would provide more predictable platelet inhibition than clopidogrel in elderly populations, without the risk of bleeding entailed by the full 10-mg dose.

Such was the hypothesis of this study that will be published soon in Circulation. However, no difference was observed as regards the primary endpoint, which warranted an early stop for study futility after an interim analysis.

Patients >74 years with acute coronary syndrome and undergoing angioplasty were randomized to a 5-mg dose of prasugrel vs. a 75-mg dose of clopidogrel. The primary endpoint was a composite of death, infarction, disabling stroke, and re-hospitalization for cardiovascular causes or bleeding within one year from the index procedure. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel, but enrolment was interrupted after 1443 patients (40% women, mean age 80 years old) had been recruited, when the interim analysis showed no difference in terms of efficacy.

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The primary endpoint occurred in 17% of all elderly patients who received prasugrel vs. 16.6% of those who received clopidogrel (hazard ratio [HR]: 1.007; confidence interval [CI]: 0.78 to 1.3; p = 0.95).

Definite/probable stent thrombosis rates were 0.7% for the prasugrel arm vs. 1.9% for the clopidogrel arm (odds ratio [OR]: 0.36; CI: 0.13-1.00; p = 0.06). The occurrence of bleeding cases considered as Bleeding Academic Research Consortium types ≥2 was 4.1% with prasugrel vs. 2.7% with clopidogrel (OR: 1.52; CI: 0.85-3.16; p = 0.18).

Conclusion

In elderly patients undergoing acute coronary syndrome, reduced-dose prasugrel (5 mg) treatment offers no benefit in terms of efficacy or safety when compared with standard-dose clopidogrel.

Original title: A Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients with Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization.

Reference: Savonitto S et al. Circulation. 2018. Epub ahead of print.

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