A reduced dose of prasugrel compared with the standard dose of ticagrelor was associated with maintained anti-ischemic efficacy and safety in elderly or low-weight patients with acute coronary syndrome (ACS), according to a study published in the Annals of Internal Medicine.1

This was an analysis of the data of 3997 patients with ACS enrolled in a multicenter, randomized study (Intracoronary Stenting and AntiThrombotic Regimen: Rapid Early Action for Coronary Treatment 5 [ISAR-REACT 5]; ClinicalTrials.gov Identifier: NCT01944800). The participants were randomly assigned to receive a standard dose of ticagrelor or prasugrel (reduced dose in the elderly or low-weight group; standard dose for other participants).

In this cohort, 1099 patients were ≥75 years (ie, elderly) or weighed <60 kg (ie, low-weight).  The efficacy end point was a composite of death, myocardial infarction, or stroke at 12 months after randomization. The safety end point was Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding.

The efficacy end point occurred in 12.7% of patients who received prasugrel and in 14.6% of patients who received ticagrelor (hazard ratio [HR], 0.82; 95% CI, 0.60-1.14) in the elderly or low-weight group. The efficacy end point occurred in 4.8% of patients who received prasugrel and in 7.3% of patients who received ticagrelor (HR, 0.65; 95% CI, 0.48-0.88; P for interaction >.2) in the neither elderly nor low-weight group.


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In the elderly or low-weight group, BARC type 3 to 5 bleeding occurred in 8.1% of patients who received prasugrel and in 10.6% of those who received ticagrelor (HR, 0.72; 95% CI, 0.46-1.12), and in 3.7% and 3.8% of patients who received prasugrel and ticagrelor, respectively, in the neither elderly nor low-weight group (HR, 0.98; 95% CI, 0.65 to 1.47; P for interaction >.2).

Study limitations include the fact that the results are based on a subgroup analysis, and that there was no formal stratification for age and weight characteristics during randomization.

“Consistent with the results of the primary trial, in younger patients aged (<75 years) with a body weight of 60 kg or more, prasugrel at a maintenance dose of 10 mg was associated with significantly lower risk for ischemic complications at 1 year after enrollment in the trial compared with ticagrelor,” noted the study authors. “With respect to all bleeding events, there was a treatment effect-by-study group interaction, suggesting that the reduced dose of prasugrel prevented the excess risk for bleeding previously observed with the full dose of prasugrel in patients aged 75 years or older or with a body weight less than 60 kg, which might have been a disadvantage compared with ticagrelor.”

The results of the ISAR-REACT 5 trial “clearly underscore how indirect comparisons across different trials may be misleading, highlighting the importance of adequately powered, randomized, head-to-head comparisons to define effective and safe treatment strategies,” noted the authors of an accompanying editorial.2 “The presented data identify the need for even better strategies to reduce the risk in this growing patient population.”

Disclosures: Some of the study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.

References

1. Menichelli M, Neumann F-J, Ndrepepa G, et al. Age- and weight-adapted dose of prasugrel versus standard dose of ticagrelor in patients with acute coronary syndromes: Results from a randomized trial [published online July 21, 2020]. Ann Intern Med. doi:10.7326/M20-1806

2. Conen D, Devereaux PJ. The value of large randomized trials of two active interventions to define the optimal treatment in patients with acute coronary syndrome [published online July 21, 2020]. Ann Intern Med. doi:10.7326/M20-4770