Smaller prasugrel dose maintains protective benefits vs. standard ticagrelor dose in ACS
A reduced dose of prasugrel in patients with ACS maintained its anti-ischemic effect without elevated bleeding risk compared with patients treated with a standard dose of ticagrelor, regardless of age or weight, researchers found.
ISAR-REACT 5 trial
In the ISAR-REACT 5 randomized trial, Maurizio Menichelli, MD, head of cardiology at Fabrizio Spaziani Hospital in Frosinone, Italy, and colleagues analyzed data from 3,997 patients who were hospitalized for ACS and would undergo PCI or diagnostic coronary angiography if needed.
Original results from ISAR-REACT 5 were presented at the European Society of Cardiology Congress in 2019 and simultaneously published in The New England Journal of Medicine. As Healio previously reported, the rate of death, MI or stroke was significantly reduced at 1 year with prasugrel (Effient, Daiichi Sankyo/Eli Lilly) compared with ticagrelor (Brilinta, AstraZeneca) without an increase in major bleeding in patients with ACS with or without ST-segment elevation.
All patients were assigned ticagrelor or prasugrel. The ticagrelor group was given a loading dose of 180 mg after randomization, then 90 mg twice per day. Patients assigned prasugrel with were given a loading dose of 60 mg, then 10 mg once per day. In the prasugrel group, those with STEMI received their loading dose soon after randomization, while those with non-STEMI or unstable angina received their loading dose after diagnostic angiography but before PCI.
Patients were categorized as 75 years or older or with body weight less than 60 kg (n = 1,099) or as younger than 75 years with body weight of 60 kg or greater (n = 2,898).
The efficacy endpoint was a composite of MI, death or stroke 12 months after randomization. The safety endpoint was Bleeding Academic Research Consortium type 3 to 5 bleeding. Patients were followed up at 30 days, 6 months and 12 months.
For patients in the older or low-weight group, the efficacy endpoint occurred in 12.7% of patients in the prasugrel group and 14.6% of those in the ticagrelor group (HR = 0.82; 95% CI, 0.6-1.14). In the group of patients who were neither older nor had low weight, the efficacy endpoint was observed in 4.8% of patients assigned prasugrel vs. 7.3% of those assigned ticagrelor (HR = 0.65; 95% CI, 0.48-0.88; P for interaction > .2).
The bleeding endpoint in the older or low-weight group occurred in 8.1% of patients assigned prasugrel compared with 10.6% of those assigned ticagrelor (HR = 0.72; 95% CI, 0.46-1.12). When assessing patients who were neither old or had low weight, the bleeding endpoint occurred in 3.7% of patients assigned prasugrel and 3.8% in those assigned ticagrelor (HR = 0.98; 95% CI, 0.65-1.47; P for interaction > .2).
“These findings suggested that reduced dose of prasugrel is adequate in these two categories of patients because it may reduce the risk for bleeding while maintaining efficacy,” Menichelli and colleagues wrote. “Given the increased risk for bleeding in elderly patients or those with a low body weight, the use of a standard dose of prasugrel in [the] current study could have markedly increased bleeding events, minimizing the net clinical benefit in elderly patients or those weighing less than 60 kg.”
Need for better strategies
In a related editorial, David Conen, MD, MPH, associate professor of medicine (cardiology) at McMaster University in Hamilton, Ontario, Canada, and P.J. Devereaux, MD, PhD, director of the division of cardiology at McMaster University in Ontario, Canada, and scientific leader of the anesthesiology, perioperative medicine and surgical research group at the Population Health Research Institute in Hamilton, wrote, “Their current analyses suggest that the prasugrel dose reduction regimen for elderly or underweight patients with ACS is effective and safe. Nevertheless, these patients continue to have a higher risk for adverse events than younger and normal-weight patients, regardless of the treatment strategy. The presented data identify the need for even better strategies to reduce the risk in this growing patient population.”