August 28, 2013
One Size Doesn’t Fit All Ages in ACS Therapy, Duke Researchers Say

Durham, NC—Age makes a difference in treatment for acute coronary syndromes (ACS), according to a new Duke University study that looks at the challenges in determining optimal dosages for older heart patients.

The report, publishing recently in the journal Circulation, notes that, for some patients older than age 75, a half-dose of the antiplatelet drug prasugrel works about as well as the typical dosage of clopidogrel. For the study, researchers looked at a substudy of the industry-supported TRILOGY-ACS Trial.

“As people live longer throughout the world, it’s increasingly important to establish appropriate treatments for conditions such as acute coronary syndromes that commonly occur later in life,” said lead author Matthew T. Roe, MD, MHS, associate professor of medicine at Duke. “These patients are very vulnerable to side effects, including bleeding, if therapies are not properly dosed. Additionally, existing practice guidelines have few specific recommendations for older patients with acute coronary syndromes as little evidence has been accrued from prior clinical trials in this population.”

While those older than age 75 are less than 10% of the U.S. population, they make up 35% of patients with ACS, according to background in the study. The authors write that different treatment modalities may be required for that group, as opposed to younger patients.

The report notes, for example, that an earlier study indicated that the platelet inhibitor prasugrel reduced the risk of adverse outcomes compared with clopidogrel in ACS patients undergoing coronary stent implantation. While those studies used a 60-mg initial dose followed by a 10-mg/day maintenance dose, patients older than age 75 at that dosage level had an increased risk of intracranial and fatal bleeding, as did younger patients weighing 132 pounds or less. The results led to warnings by the FDA and the European Medicines Agency about the use of the 10-mg/day maintenance dose of prasugrel in those populations; the groups said a reduced dose of 5 mg/day should be considered to mitigate bleeding complications.

To determine the effectiveness of the lower dosage in that group, researchers in the Duke study analyzed more than 2,000 older patients in the TRILOGY ACS trial that compared prasugrel with clopidogrel to manage ACS without coronary stent implantation or coronary bypass surgery. They determined that a smaller dosage of 5 mg/day of prasugrel presented no greater risk of bleeding problems than the commonly prescribed 75-mg dose of clopidogrel in the elderly population.

“The findings from our study indicate how difficult it is to identify the right dose of anti-clotting medications for the elderly, to improve outcomes after a heart attack,” said coauthor Magnus Ohman, MD, professor of medicine at Duke and chairman of the TRILOGY ACS study. “While a lower dose seemed intuitive, it was safe but not more effective. Future dedicated studies need to continue to find the right therapies for the vulnerable elderly patients.”

U.S. Pharmacist Social Connect