PROMETHEUS Data Compare Use of Prasugrel and Clopidogrel in Real-World Practice

May 8, 2015—Results of the PROMETHEUS study were presented as a late-breaking clinical trial at the Society for Cardiovascular Angiography and Interventions (SCAI) 2015 scientific sessions being held May 6–9 in San Diego, California.

SCAI announced that the presentation titled “90-Day Effectiveness and Safety of Prasugrel Versus Clopidogrel as Used in Clinical Practice in Patients with Acute Coronary Syndrome (ACS) Undergoing Percutaneous Coronary Intervention (PCI): Initial Findings from the PROMETHEUS Study” was delivered by coprincipal investigator Usman Baber, MD. Dr Baber is Assistant Professor of Cardiology at Mount Sinai Hospital in New York, New York.

According to SCAI, as newer antiplatelet medications become available, little is known about the actual use of the drugs in clinical practice. Prasugrel (Effient; Eli Lilly and Company and Daiichi Sankyo Company, Ltd) was approved by the US Food and Drug Administration in 2009 to treat ACS patients undergoing PCI. Compared to clopidogrel, studies showed prasugrel reduces the risk of thrombotic events but is associated with an increased risk of bleeding. 

As summarized by SCAI, the PROMETHEUS investigators reviewed data in 19,914 heart disease patients undergoing PCI with stenting at eight academic medical centers in the United States between January 2010 and June 2013. For patients receiving either prasugrel or clopidogrel, the investigators reviewed data on major adverse cardiac events (MACE; including death, heart attack, stroke, or unplanned revascularization) and bleeding requiring hospitalization within 90 days of PCI. 

In the press release, Dr. Baber commented, “Data examining the use, safety, and efficacy of these drugs in ‘real-world’ patients not enrolled in randomized trials remains limited. Results from our study provide insight on both clinical decision-making and the risk/benefit profile surrounding prasugrel use at the time of PCI in ACS patients.”

In PROMETHEUS, 4,058 patients (20.4%) received prasugrel at the time of PCI. These patients tended to be younger, more often male, and had less renal dysfunction and anemia than patients receiving clopidogrel (n = 15,856). However, the prasugrel patients also were more likely to present with ST-elevation myocardial infarction and to receive longer stents. 

After 90 days, patients receiving prasugrel had lower rates of adverse events than patients receiving clopidogrel (9.6% vs 5.7%; P < .001), translating to a large (42%) relative reduction favoring prasugrel. After adjusting for baseline differences, however, this reduction was attenuated to a more modest and nonsignificant 11% benefit. Analogously, adjusted bleeding rates were not significantly different between groups. 

“Overall we found substantial differences in patient profiles receiving prasugrel as compared to clopidogrel. Risk factors for both ischemic and hemorrhagic complications were much lower in prasugrel-treated patients. Used in this manner, the benefit of prasugrel in lowering ischemic events was attenuated while harm in terms of bleeding risk was also minimized,” concluded Dr. Baber in the SCAI press release.