An article published Online First and in a future edition of The Lancet reports that proton pump inhibitors (PPIs) do not interfere with the clinical benefit of the anticlotting drugs clopidogrel or prasugrel (thienopyridines) in patients after an acute coronary syndrome such as heart attack or unstable angina. PPIs are a commonly prescribed antacid medication. The article is the work of Dr Michelle O’Donoghue, Brigham and Women’s Hospital, Boston, MA, USA, and colleagues. These findings are quite the opposite of the conclusions of other recent studies that have confirmed that there is potential harm when these two classes of drugs are combined.

As part of a strategy that is authorized by current guidelines, PPIs are often administered with clopidogrel and prasugrel to help reduce the risk of gastrointestinal bleeding. However a number of studies have warned that PPIs could counteract the clinical benefit of clopidogrel. The authors studied the effects of PPIs in the TRITON-TIMI 38 trial, and one other smaller trial. A total 13,608 patients were enrolled in the TRITON-TIMI 38 trial. They had suffered a heart attack or unstable angina. They were randomly assigned them to clopidogrel or prasugrel. Findings showed that the use of a PPI in combination with these drugs did not increase the risk of cardiovascular events, including death, heart attack, or stroke.

The authors write in conclusion: “The current findings do not support the need to avoid concomitant use of proton pump inhibitors, when clinically indicated, in patients receiving clopidogrel or prasugrel.”

In an associated note, Dr Dirk Sibbing and Dr Adnan Kastrati, Technische Universität München, Munich, Germany, approve that patients with a risk profile comparable to those patients in the TRITON-TIMI 38 study can be safely treated with a proton pump inhibitor on top of clopidogrel or prasugrel. They remark: “Caution is however required when prescribing proton pump inhibitors in selected high risk patients with intrinsic reduced response to thienopyridines.”

“Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials”
Michelle L O’Donoghue, Eugene Braunwald, Elliott M Antman, Sabina A Murphy, Eric R Bates, Yoseph Rozenman, Alan D Michelson, Raymond W Hautvast, Peter N Ver Lee, Sandra L Close, Lei Shen, Jessica L Mega, Marc S Sabatine, Stephen D Wiviott
DOI: 10.1016/S0140-6736(09)61525-7
The Lancet

Written by Stephanie Brunner (B.A.)