Prasugrel, Ticagrelor Give Similar Short-term Outcomes After Primary PCI: PRAGUE-18

ROME, Italy—The choice of prasugrel or ticagrelor for patients with acute MI undergoing primary PCI may make little difference, at least in the short term, suggest results from the PRAGUE-18 trial.

In the prematurely terminated and underpowered study, there were no differences between the antiplatelet drugs in terms of composite clinical outcomes through 7 or 30 days, Petr Widimsky, MD, PhD (Charles University, Prague, Czech Republic), reported here at the European Society of Cardiology Congress 2016. The findings were published simultaneously online in Circulation, with Zuzana Motovska, MD, PhD (Charles University), as lead author.

“Based on these results, probably both drugs are . . . almost equal or very similar,” Widimsky said. 

Keith Fox, MBChB (Edinburgh Centre for Cardiovascular Science, Scotland), who served as a discussant after Widimsky’s presentation, congratulated the investigators on performing a trial many thought would not be possible but urged caution in interpreting the results, pointing to issues surrounding futility assessments based on limited data and the lack of statistical power to definitively compare outcomes between the two drugs.

“A large trial would need to be conducted to answer the planned questions definitively,” he said. Fox added that he thinks such a trial can be completed using registry-based enrollment and follow-up facilitated by linking electronic medical records and national mortality registries, as was done in TASTE, for example.

“I think that there are great opportunities to carry this forward,” Fox said.

In their paper, the investigators acknowledge the need for confirmation in a larger trial, although Widimsky said, “for me, as a clinician, the answer is quite clear,” despite the trial’s limitations.

Lack of Head-to-Head Data

A randomized, head-to-head comparison of prasugrel (Effient; Eli Lilly) and ticagrelor (Brilinta; AstraZeneca) had never been performed, leaving it up to physician discretion which drug to choose. Both medications maintain equal footing in the guidelines, although there are recommendations against using prasugrel in patients with a history of stroke or transient ischemic attack.

To evaluate whether there are differences between the drugs in terms of outcomes, the researchers randomized patients with STEMI (or NSTEMI with ongoing ischemia) undergoing primary PCI to receive prasugrel 60 mg followed by 10 mg/day (5 mg/day if older than 75 or less than 60 kg) or ticagrelor 180 mg followed by 90 mg twice daily. Maintenance therapy was used for 1 year.

The target enrollment was 2,500 patients, although the trial was stopped prematurely for futility after only 1,230 patients were enrolled at 14 sites in the Czech Republic.

The primary endpoint (death, reinfarction, urgent TVR, stroke, serious bleeding requiring transfusion, or prolonged hospitalization) was assessed at 7 days or hospital discharge (whichever came first) to eliminate the impact of patients switching to clopidogrel after discharge. Widimsky explained that some patients chose to switch to clopidogrel because the costs of that drug—but not of prasugrel or ticagrelor—are fully covered within the healthcare system in the Czech Republic.

There was no difference in the rate of the primary endpoint between the prasugrel and ticagrelor groups (4.0% vs 4.1%; OR 0.98; 95% CI 0.55-1.73) and similarly, no difference in the key secondary endpoint of cardiovascular death, MI, or stroke at 30 days (2.7% vs 2.5%; OR 1.06; 95% CI 0.53-2.15).

Widimsky said the final 1-year results of the trial will be presented sometime next year and will include information about outcomes in patients who chose to start taking clopidogrel after discharge.

Source:

• Motovska Z, Hlinomaz O, Miklik R, et al. Prasugrel versus ticagrelor in patients with acute myocardial infarction treated with primary percutaneous coronary intervention: multicenter randomized PRAGUE-18 study. Circulation. 2016;Epub ahead of print.

Disclosures:

• Administrative costs for the study were covered by the Charles University Cardiovascular Research Program P35.
• Widimsky reports receiving honoraria from AstraZeneca, Eli Lilly, and Daiichi Sankyo.
• Motovska reports receiving speaking and advisory board fees from AstraZeneca and Eli Lilly.

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