I am interested in your opinions about the result of the ISAR-REACT 5 trial, which was published in 2019 (N Engl J Med. 2019 Oct 17;381(16):1524-1534).
ISAR-REACT 5 randomized more than 4.000 patients to receive either Prasugrel or Ticagrelor after an acute coronary syndrome. The primary endpoint was the composite of death, myocardial infarction or stroke at 1 year.
The sample size calculation was based on the following assumptions:
- the incidence of the primary endpoint would be 10.0% in the ticagrelor group
- the incidence of the primary endpoint would be 12.9% in the prasugrel group
- 80% power to detect a relative risk that was lower by 22.5% in the rate of the primary end point in the ticagrelor group as compared with the prasugrel group
- two-sided alpha level of 0.05
The result of the trial was a hazard ratio of 1.36 with a 95% confidence interval ranging from 1.09 to 1.70 in favor for prasugrel. This is in contrast to the assumptions of the sample size calculation.
The authors concluded “Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor […]”.
Bittl et al just recently published an editorial on a substudy of the ISAR-REACT 5 trial (JACC Cardiovasc Interv. 2020 Oct 12;13(19):2248-2250). The authors of the editorial proposed that “[…] the findings in ISAR-REACT 5 […] were statistical false positives” because “[…] the ISAR-REACT 5 investigators believed that ticagrelor would have been superior. If they thought that there was only a 10% prior probability (i.e., 1:9 odds) that prasugrel could outperform ticagrelor, the “significant” outcome in favor of prasugrel has only a 64% chance of being a true positive, […]”. This statement is followed by a calculation leading the chance of 64%.
What do you thing about this? Is it okay to conclude from the ISAR-REACT 5 trial that Prasugrel is superior over Ticagrelor from a statistical point of view?
I would be happy to read your thoughts!