SCAI.15: In practice, prasugrel use may not mimic trials

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 - Medication Management

Cardiologists in real-world practice may not be optimizing the benefit of prasugrel in patients undergoing PCI but they also don’t appear to be putting them in harm’s way, according to results released May 8 at the Society for Cardiovascular Angiography and Interventions (SCAI) 2015 scientific sessions in San Diego.

“The therapeutic benefit is more modest in terms of reducing [thrombotic risk] compared to what we have seen in randomized data,” said Usman Baber, MD, MS, an assistant professor of cardiology at Mount Sinai Hospital in New York, at a press briefing for late-breaking clinical trials. “However, simultaneously we see no significant increased risk of bleeding when used in this manner.”

Baber presented findings from PROMETHEUS, a registry-based study that compared the use of prasugrel (Effient, Daiichi Sankyo) and clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) in patients with acute coronary syndrome (ACS) who received PCI at eight academic centers in the U.S. from 2010 and 2013. To participate, the centers needed to have a database with baseline clinical, procedural and outcome data that could be extracted and confirmed using a questionnaire.

The FDA approved prasugrel as an antiplatelet agent in 2009 to treat ACS patients undergoing PCI. The agency based its decision on randomized trials that evaluated the safety and efficacy of prasugrel compared with clopidogrel (Plavix) in reducing ischemic events. Prasugrel reduced the risk of thrombotic events but increased the risk of bleeding.

PROMETHEUS was designed to clarify how these drugs were being used in clinical practice.

The PROMETHEUS researchers provided data on almost 20,000 patients. Of those, 20 percent received prasugrel and the rest clopidogrel. Compared with the clopidogrel group, prasugrel patients as a whole were younger, more likely to be male, and less likely to have diabetes, hypertension, dyslipidemia, previous cerebrovascular disease, chronic kidney disease or anemia. They also were more likely to present with STEMI and non-STEMI.     

In unadjusted analyses, the 90-day rate of major adverse cardiovascular events—a composite of all-cause mortality, unplanned revascularization, stroke or MI—was 5.7 percent with prasugrel vs. 9.6 percent with clopidogrel. But after adjustments, the 42 percent relative reduction with prasugrel was reduced to 11 percent.

“For bleeding, we also found that prasugrel was paradoxically associated with a reduction in bleeding in unadjusted analyses,” Baber said. “But again, with the baseline differences, we found no statistical differences in bleeding rates between the two groups.”

Registry studies such as PROMETHEUS help identify practice patterns and gaps going forward, Baber said. “What we are learning from these types of registry studies is that we need to develop appropriate risk stratification models” to pinpoint who gains the greatest benefit or faces the most risk with this therapy. “We don’t know quite yet how to do that, but the data from these types of registries will help inform those kinds of decisions.”