Proton pump inhibitors are appropriate in patients who have multiple risk factors for gastrointestinal bleeding and who require antiplatelet therapy, according to an updated expert consensus report published online Nov. 8 simultaneously by the American College of Cardiology Foundation, the American College of Gastroenterology, and the American Heart Association.
The last consensus report, released in 2008, recommended the use of PPIs to prevent GI bleeding events in patients taking antiplatelet agents, but subsequent clinical experience and research raised concerns about an adverse interaction between the two classes of drugs. Since then, "it has been difficult for practitioners to assimilate this flood of information and to develop optimal treatment strategies for managing patients who might benefit from antiplatelet therapy, yet who might suffer from GI bleeding," said Dr. Neena S. Abraham, chair of the report’s writing committee, and her associates.
"Our goal was to carefully evaluate recent studies that suggested a potential dangerous interaction between PPIs and thienopyridines, in order to provide clinicians with a pragmatic, evidence-based approach for safer prescribing of antiplatelet drugs, especially among patients in whom the risk-benefit ratio requires a careful assessment," Dr. Abraham, a gastroenterologist at the Michael E. DeBakey VA Medical Center and associate professor of medicine at Baylor College of Medicine, both in Houston, said in a press statement accompanying the consensus document.
The 2010 report "summarizes the best evidence and incorporates the expert clinical viewpoints of both cardiologists and gastroenterologists, who face this dilemma on a daily basis," she noted.
Dr. Neena S. Abraham
Among the new consensus statement’s findings are the following:
• PPIs are recommended to reduce GI bleeding in patients with a history of such bleeding, as well as in those with multiple risk factors for GI bleeding, such as a history of peptic ulcer disease; advanced age; use of anticoagulants, steroids, or NSAIDs; and Helicobacter pylori infection.
• Routine use of PPIs is not recommended for patients who are at lower risk of GI bleeding and have much less potential to benefit from prophylactic therapy.
• Clinical decisions regarding combined therapy must balance overall risks and benefits, considering both cardiovascular and gastrointestinal complications.
• Research suggests that concomitant use of clopidogrel in particular and a PPI reduces clopidogrel’s antiplatelet effects. However, it has not been established whether the changes in surrogate end points, such as platelet assays, used in these studies translate into clinically meaningful differences.
• Observational studies and one randomized clinical trial have shown inconsistent effects on cardiovascular outcomes when thienopyridines and PPIs are combined. It is possible that a clinically important interaction does occur, particularly in certain subgroups such as patients who metabolize clopidogrel poorly.
• Pharmacogenomic testing (for example, to identify patients with impaired metabolism of antiplatelet drugs) and platelet function testing might prove to be helpful in managing combined therapy, but that has not yet been established.
• Drug interactions might be minimized by separating the dosing of the two agents, but as of now there is no solid evidence to recommend such dosing alterations.
Overall, PPIs should be prescribed in tandem with antiplatelet drugs for only one indication: to reduce the increased risk of GI complications caused by antiplatelet drugs, the report concludes (J. Am. Coll. Cardiol. 2010 Nov. 8 [doi:10.1016/j.jacc.2010.09.010]).
Dr. Mark A. Hlatky, vice chair of the consensus statement’s writing committee and a cardiologist at Stanford (Calif.) University, said in the press statement that the combined use of PPIs and antiplatelet drugs "must be individualized, not done as a matter of routine."
"The risk of GI bleeding varies among individuals, as does the risk of cardiac events," he noted.
The work of the consensus document writing committee was supported exclusively by the American College of Cardiology Foundation, with no industry support.