Michelle L. O'Donoghue, M.D., of Brigham and Women's Hospital in Boston, and colleagues analyzed two trials: the PRINCIPLE-TIMI 44 trial, in which 201 patients undergoing elective percutaneous coronary intervention were randomly assigned to prasugrel or high-dose clopidogrel; and the TRITON-TIMI 38 trial, in which 13,608 patients with an acute coronary syndrome were randomly assigned to prasugrel or clopidogrel.
In the first trial, the researchers found that PPI use was associated with significantly lower inhibition of platelet aggregation after clopidogrel loading, but a more modest inhibition of platelet aggregation after prasugrel loading. In the second trial, they observed no association between PPI use and the primary end point -- a composite of cardiovascular death, myocardial infarction, or stroke -- for patients treated with clopidogrel or prasugrel (adjusted hazard ratios, 0.94 and 1.00, respectively).
"Although only a randomized trial of PPI use can definitively establish the clinical implications of combining a PPI with a thienopyridine, our findings do not support the need to avoid concomitant use of PPIs for gastric protection in patients receiving thienopyridine therapy who are at increased risk for gastrointestinal bleeding," the authors conclude.
Daiichi Sankyo and Eli Lilly sponsored the two trials; several co-authors reported financial relationships with the companies.
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