The first head-to-head comparison of prasugrel and ticagrelor shows similar efficacy and safety of the two antiplatelet agents in patients with ST segment elevation MI (STEMI) undergoing primary PCI.

Findings of the PRAGUE-18 trial, presented at the European Society of Cardiology (ESC) Congress 2016, showed no difference in rates of the primary composite endpoint of death, reinfarction, stroke, urgent target vessel revascularization, serious bleeding requiring transfusion, or prolonged hospitalization at 7 days between patients treated with prasugrel or ticagrelor (4.0 vs 4.1 percent; p=0.935). [Circulation 2016, doi: http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024823]

The rate of the key secondary endpoint of cardiovascular death, nonfatal MI or stroke at 30 days also did not differ significantly between prasugrel and ticagrelor recipients (2.7 vs 2.5 percent; p=0.864).

“Our results offer clinicians greater freedom in the selection of antiplatelet agent for patients with STEMI who receive dual antiplatelet therapy,” said investigator Dr. Petr Widimsky of the Cardiocenter of Charles University in Prague, Czech Republic.

However, others suggested that the design and power of the study made it difficult to draw firm conclusions.

The PRAGUE-18 trial was a purely academic study that included 1,230 patients with STEMI recruited from 14 Czech centres. Upon arrival at the PCI centre, the patients were randomized immediately to receive prasugrel 60 mg followed by 10 mg/day (5 mg/day if age >75 years or body weight <60 kg) for 1 year, or ticagrelor 180 mg followed by 90 mg twice daily for 1 year.

“As per local healthcare regulations, patients had to cover the costs of prasugrel or ticagrelor after hospital discharge. Thus, some patients decided to switch to clopidogrel, which is fully covered by local healthcare, after hospital discharge,” said Widimsky.

Among 634 patients randomized to receive prasugrel, 28 switched to clopidogrel before day 7, while 135 switched between days 7 and 30. In the ticagrelor group (n=596), 29 patients switched to clopidogrel before day 7, while 185 switched between days 7 and 30. “Prasugrel and ticagrelor were continued beyond day 30 or until death in 74 and 64 percent of the patients, respectively,” noted Widimsky.

“Furthermore, the trial was underpowered by design. The planned number of patients was 2,500. However, to show a 25 percent difference between the two arms with a 4 percent event rate and 90 percent power, a total of 14,190 patients would be required,” pointed out discussant Dr Keith Fox of the Edinburgh Centre for Cardiovascular Science in Scotland.

“Also, the trial was terminated prematurely for futility after only 1,230 patients were randomized. No confidence bounds were presented, and the confidence bounds would likely be very wide due to the lack of statistical power,” Fox continued. “Therefore, I do think we need to be cautious about the investigators’ conclusion.”