In ACS patients who undergo stenting, prasugrel does not increase serious bleeding compared with clopidogrel, according to an analysis of US clinical practice presented May 8, 2015, at the Society for Cardiovascular Angiography and Interventions Scientific Sessions in San Diego, CA. But the issue of whether the more potent antiplatelet drug—which is used predominantly in those at lower risk—reduces ischemic events remains clouded by likely confounding.

Investigators led by Usman Baber, MD, of Mount Sinai Hospital (New York, NY), looked at 19,914 ACS patients (mean age about 62 years; 31.7% women) who underwent stenting at 8 US centers from January 2010 through June 2013. Clinical presentation was unstable angina in 56% of patients, NSTEMI in 27%, and STEMI in 17%.

Overall, 20% received prasugrel (Effient; Daiichi Sankyo/Eli Lilly) and the rest received clopidogrel. Compared with the clopidogrel-treated patients, prasugrel-treated patients were implanted more often with at least 1 second-generation DES (81.2% vs 66.4%) and less often with a BMS (14.0% vs 24.8%; both P < .05).

Compared with patients receiving clopidogrel, prasugrel-treated patients were younger, more often male, and less likely to have renal dysfunction or anemia (all P < .0001). Conversely, prasugrel was more apt to be used in patients with STEMI or receiving longer stents.

Advantage of Prasugrel Canceled by Adjustment

At 90 days, the risks of MACE (all-cause death, MI, stroke, or unplanned revascularization; primary endpoint), all-cause death, MI, and clinically overt hemorrhage requiring hospitalization were all substantially reduced with prasugrel vs clopidogrel. After adjustment, however, only all-cause death remained lower with the more potent agent (table 1).

Table 1. Outcomes at 90 Days: Prasugrel vs Clopidogrel^a

^aAll adjustment performed via propensity-score stratification; other adjustment methods yielded similar results. 

In addition to the study’s observational design, Dr. Baber acknowledged other limitations, including a lack of information about medication adherence and the potential impact of crossover between therapies.

“Overall, we found substantial differences in the profiles [of patients] receiving prasugrel as compared to clopidogrel,” Dr. Baber said in a press release. “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.”

In fact, the absence of a difference in bleeding risk between prasugrel and clopidogrel after adjustment “may reflect selection of patients at very low risk for hemorrhagic complications,” he noted in his presentation.

Questions About Prasugrel Use Persist

In a press conference, Dr. Baber said the wide variability among medical centers in the pattern of antiplatelet prescription “probably reflects the real world, with some hospitals more comfortable in using prasugrel than others.”

Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital (Boston, MA), told TCTMD in a telephone interview that the heterogeneity suggests practitioners “still have a lot of questions about which patients should get which form of antiplatelet therapy.”

Dr. Bhatt said he did not give much weight to the head-to-head comparison between the drugs. With nonrandomized data, it is impossible to determine whether prasugrel really offers better outcomes, he noted. The fact that events were reduced by a large and “unrealistic” amount in unadjusted analyses but not after adjustment underscores the influence of confounding and “argues that there is no real difference,” he said.

On the other hand, prasugrel’s efficacy was likely diluted by its use in “unstable angina” patients who were troponin-negative and not truly at high risk, Dr. Bhatt observed. He explained that in randomized studies, the clearest benefit of prasugrel was seen in patients who were troponin-positive—especially those with STEMI or NSTEMI.

Feasible to Dovetail Use With Risk?

In his presentation, Dr. Baber suggested that “[r]ecalibrating ‘real-world’ use of prasugrel to better approximate a patient’s ischemic risk may yield a more appreciable therapeutic benefit. Broader use of prasugrel in eligible patients may achieve the therapeutic results seen in clinical trials.”

Better targeting of patients at high ischemic risk and low bleeding risk is an admirable goal, Dr. Bhatt agreed, but one that is challenging because both risks often coexist in individual patients.

In the end, Dr. Bhatt said, the data provide “a snapshot of… practice, but I wouldn’t do anything different based on them. All we can say is that there is a fair amount of variability in how doctors choose to use prasugrel or clopidogrel. This [study] cannot tell whether their choices are right or wrong.”

Perhaps the most important finding is the absence of excess bleeding with prasugrel, Dr. Bhatt suggested. Because patients who received the drug tended to be younger and healthier, it would have been “alarming” had they experienced more bleeding than those given clopidogrel, he noted. “It would have meant that the safety signal seen in the randomized trials was amplified in the real world. That this was not the case provides some reassurance.”

Note: Co-principal investigator Roxana Mehran, MD, is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.

Baber U. Clinical assessment of patients with acute coronary syndrome managed with percutaneous coronary intervention and treated with prasugrel or clopidogrel using academic center databases: the PROMETHEUS study. Presented at: Society for Cardiovascular Angiography and Interventions Scientific Sessions; May 8, 2015; San Diego, CA.

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• TRITON-TIMI 38: Prasugrel Better Than Clopidogrel for Preventing MI
• Prasugrel Inhibits Platelet Function Better Than Clopidogrel in ACS Patients