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Expert consensus document offers suggestions on concomitant PPI, antiplatelet drug use
Abraham N. J Am Coll Cardiol. 2010;doi:10.1016/j.jacc.2010.09.010.
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The American College of Cardiology, American College of Gastroenterology and the American Heart Association have jointly released an expert consensus document supporting an individualized approach to determine whether concomitant use of proton pump inhibitors and thienopyridines is appropriate in patients with acute coronary syndromes.
“The magnitude of [antiplatelet drug] benefits and risks in individual patients varies depending on their characteristics,” Neena S. Abraham, MD, chair of the document’s writing committee, and fellow colleagues wrote. “The challenge for health care providers is to determine the risk/benefit balance for individual patients or subsets of the target population.”
Among the evidence presented in the consensus document included data from pharmacokinetic and pharmacodynamic studies, which suggested that concomitant use of a proton pump inhibitor (PPI) and clopidogrel reduces the antiplatelet effects of clopidogrel.
Other observational studies and a single randomized clinical trial, the investigators said, have shown inconsistent effects on CV outcome when thienopyridines are taken with PPIs. In the latter case, however, “a clinically important interaction cannot be excluded, particularly in certain subgroups, such as poor metabolizers of clopidogrel,” they wrote. “Clinical decisions regarding concomitant use of PPIs and thienopyridines must balance overall risks and benefits, considering both CV and gastrointestinal complications.”
According to the document, factors that raise the risk for gastrointestinal bleeding with antiplatelet therapy and that should guide suggestions of concomitant use of PPIs include advanced age, Helicobacter pylori infection and concomitant use of warfarin, steroids or NSAIDs. However, PPI use was not recommended for patients at lower risk for upper gastrointestinal bleeding or who have much less potential to benefit from prophylactic therapy.
For physicians assessing the clinical interaction between PPIs and thienopyridines, the investigators said to keep four considerations in mind: the strength of the association, which in observational studies was small to moderate (HR<2); the consistency of the association across different samples; the existence of a biologically plausible mechanism of action, such as the vitro testing, which suggests that PPIs may inhibit CYP2C19 metabolism, a factor shown to increase CV event rate; and the supportive experimental evidence, including pharmacodynamic studies.
The investigators said addressing the many gaps in knowledge that still remain involving gastrointestinal bleeding in patients prescribed thienopyridines are areas for future research.
“There is considerable variation among patients in response to antiplatelet therapy, so the potential role of laboratory testing in individualization of therapy should be a high priority for research,” Abraham and colleagues wrote. “Either pharmacogenomic testing for CYP2C19 variants or platelet function testing might be used to tailor therapy by guiding the choice of drug (thienopyridines, PPIs, H2 receptor antagonists), the choice of drug dose or both.”
Although the concept of individually tailored therapy is rational and attractive, they said, empirical evidence for this approach is sparse, necessitating clinical studies and randomized trials comparing guided therapy with usual care.
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