Recent prospective trials have shown that concomitant use of clopidogrel and proton-pump inhibitors (PPIs) is not associated with significant adverse cardiovascular outcomes (JW Gastroenterol Oct 16 2009). Despite such findings, warnings that these agents should not be used in combination persist from government authorities such as the U.S. Food and Drug Administration and the European Medicines Agency).
To further examine outcomes associated with concurrent use of these drugs, investigators conducted a retrospective cohort study of 20,596 patients (age, ![≥]()
30) who received clopidogrel after being hospitalized for myocardial infarction, coronary revascularization, or unstable angina; of these patients, 7593 (37%) received concurrent PPI therapy. The primary endpoints were hospitalization for gastrointestinal (GI) bleeding or serious cardiovascular disease complications (myocardial infarction or sudden cardiac death, stroke, or other cardiovascular-related death) during the 7-year study period.
The adjusted incidence of hospitalization for GI bleeding was lower for patients who received clopidogrel with PPI therapy than for those who received clopidogrel without PPI therapy (hazard ratio, 0.50; 95% confidence interval, 0.39–0.65). Also, concurrent PPI therapy was not associated with significant excess risk for adverse cardiovascular effects. Of note, for patients considered to be at highest risk for GI bleeding, concurrent PPI therapy was associated with an absolute reduction of 28.5 (95% CI, 11.7–36.9) hospitalizations for bleeding per 1000 patient-years.
Comment: Although limited by its retrospective design, this study provides further evidence that the combined use of PPIs and clopidogrel is safe and effective for patients with heart disease who are deemed to be at high risk for GI complications and is not associated with potentially more-formidable cardiovascular complications. Even though all PPIs were analyzed for potential risk-associated events, the majority of patients (62%) received pantoprazole. Given the small event rates for the other PPIs, weighted recommendations for specific PPIs would not be appropriate.
— David A. Johnson, MD
Published in Journal Watch Gastroenterology April 2, 2010
