One-year Outcomes of Prasugrel Versus Ticagrelor In Acute Myocardial Infarction Treated With Primary Angioplasty: The PRAGUE-18 Study
Selected in Journal of the American College of Cardiology by F. Costa
Zuzana Motovska, Ota Hlinomaz, Petr Kala, Milan Hromadka, Jiri Knot, Ivo Varvarovsky, Jaroslav Dusek, Jiri Jarkovsky, Roman Miklik, Richard Rokyta, Frantisek Tousek, Petra Kramarikova, Michal Svoboda, Bohumil Majtan, Stanislav Simek, Marian Branny, Jan Mrozek, Pavel Cervinka, Jiri Ostransky, Petr Widimsky and PRAGUE-18 Study Group
LinkRead the abstract
Why this study – the rationale/objective?
Antiplatelet treatment is of paramount importance in the setting of acute MI. Clinical trials and international guidelines support the higher efficacy of both prasugrel and ticagrelor, as compared to clopidogrel, in patients undergoing primary PCI. Yet, wether there is a difference in the efficacy/safety profile of prasugrel vs. ticagrelor in this setting is still unknown.
How was it executed – the methodology?
The PRAGUE 18 trial was a randomized, open-label, multicenter clinical trial which included patients undergoing primary PCI in Czech Republic. Patients with acute MI treated with primary PCI were randomly assigned to prasugrel (60 mg initial dose and a maintenance dose of 10 mg daily, or 5 mg daily for those older than 75 years of age or those who weighed less than 60 kg) or to ticagrelor (180 mg initial dose and a maintenance dose of 90 mg twice daily). The study enrollment phase was terminated prematurely for futility. In the current analysis the authors presented the results for the 12 months follow-up.
What is the main result?
A total of 34.1% of patients randomized to prasugrel, and 44.4% to ticagrelor discontinued the study drug switching to clopidogrel (median time of the switching was 8 days). In the intention-to-treat analysis, the incidence of the primary efficacy endpoint at 12 months (cardiovascular death, non-fatal MI, or stroke) was 6.6% in the prasugrel group and 5.7% in the ticagrelor group (P=0.503). No significant differences for the single elements of the primary endpoint were observed. Bleeding events occurred in 10.9% of patients in the prasugrel group and in 11.1% in the ticagrelor group (P=0.930).
Critical reading and the relevance for clinical practice
This is the first investigator-initiated study which provides a face-to-face comparison of prasugrel vs. ticagrelor in patients undergoing primary PCI. The study ultimately failed to show any significant difference in efficacy/safety among the two treatments. Yet, due to multiple limitations of the study, rushing to the conclusion that there is an equipose between the two agents might be misleading for three reasons: first, the study was initially powered to detect an absolute difference of 2.5% for the primary endpoint with a power of 80%, an estimate that, even if correct, might ignore smaller clinically significant differences. Second, the study was prematurely stopped, reducing all conclusions to hypotheses. Third, a large proportion of patients did not adhere to the study medication, and this divergence occurred early during the trial, further reducing the capacity of the study to detect any difference among two antiplatelet agents.