Low-Dose Prasugrel Results in Similar Efficacy, Reduced Bleeding vs Ticagrelor

July 21, 2020

A prespecified analysis of ISAR-REACT 5 is shedding light on the effectiveness and safety of age- and weight-adjusted prasugrel versus ticagrelor following ACS.

New research suggests a reduced dose of prasugrel was as effective and associated with less bleeding when compared against ticagrelor in low-weight or elderly patients.

An analysis of data from the ISAR-REACT 5 trial, results indicated a reduced dose of prasugrel was associated with similar efficacy and could protect against the excess risk for bleeding in elderly or low-weight patients presenting with acute coronary syndrome (ACS).

To examine the effects of age- and weight-adapted dose of prasugrel compared against a standard dose of ticagrelor in patients with ACS, ISAR-REACT 5 investigators designed the current study as a prespecified analysis. With this in mind, investigators defined the efficacy end point of their study as a composite of death, myocardial infarction, or stroke at 12 months. The main safety end point of the analysis was Bleeding Academic Research Consortium (BARC) type 3-5 bleeding.

Additionally, investigators also designed the analysis to assess BARC type 1-5 bleeding, incidence of the individual components of the efficacy end point, and the incidence of stent thrombosis at 12 months.

Of the original 3997 patients in ISAR-REACT 5, 1099 were 75 years of age or older or weighed less than 60 kg. Investigators pointed out final diagnosis and drug therapy at discharge did not differentiate between the groups.

At 1 year, the composite efficacy end point occurred in 148 patients in the elderly or low-weight group and 172 among patients in the neither elderly nor low-weight group (HR, 2.37; 95% CI, 1.90-2.96; P <.001). The safety end point of BARC type 3-5 bleeding occurred in 81 patients in the elderly or low-weight group compared to 93 among patients in the neither elderly nor low-weight group (HR, 2.82; 95% CI, 2.08-3.82; P <.001).

When assessing outcomes based on treatment group, investigators found the efficacy end point occurred in 68 patients randomized to prasugrel and 80 patients randomized to ticagrelor among those in the elderly or low-weight group—yielding cumulative incidence rates of 12.7% and 14.6% for the prasugrel and ticagrelor arms, respectively (HR, 0.82; 95% CI, 0.60-1.14; P >.2). Among those in neither the elderly nor low-weight group, the cumulative incidence rates for prasugrel and ticagrelor were 4.8% and 7.3%, respectively (HR, 0.65; 95% CI, 0.48-0.88; P=.006).

Among those classified into the elderly or low-weight group, the safety end point of BARC type 3-5 bleeding occurred in 8.1% of patients reaching prasugrel and 10.6% of patients receiving ticagrelor (HR, 0.72; 95% CI, 0.46-1.12; P=.146). In comparison, rates in the neither elderly nor low-weight group were 3.7% for prasugrel and 3.8% for ticagrelor (HR, 0.98; 0.65-1.47; P >.2).

In a related editorial, David Conen, MD, MPH, and P.J. Devereaux, MD, PhD, both of the Population Health Research Institute and McMaster University Hamilton, Ontario, commend the investigators for taking the deeper dive into the effects of ticagrelor and prasugrel in a direct head-to-head setting.

“We congratulate Menichelli and colleagues for their important contribution to the management of patients with ACS. Their current analyses suggest that the prasugrel dose reduction regimen for elderly or underweight patients with ACS is effective and safe,” the pair wrote. “Nevertheless, these patients continue to have a higher risk for adverse events than younger and normal-weight patients, regardless of the treatment strategy.”

This study, “Age and Weight Dose-Adapted Prasugrel Versus Standard-Dose Ticagrelor,” was published in the Annals of Internal Medicine.