ESC: Effects of Combining PPIs and Thienopyridines Examined

Coadministration of PPI with clopidogrel or prasugrel may not increase heart risks

03 sept 2009-- In patients receiving clopidogrel or prasugrel, use of proton-pump inhibitors (PPIs) is not associated with an increased risk of cardiovascular events, according to a study published online Sept. 1 in The Lancet and presented at the European Society of Cardiology Congress 2009, held from Aug. 29 to Sept. 2 in Barcelona, Spain.

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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