The results of the Clopidogrel Medco Outcomes Study presented today during SCAI’s Annual Scientific Sessions found that patients taking both clopidogrel and a proton pump inhibitor (PPI) experienced a 50% increase in the combined risk of hospitalization for heart attack, stroke, unstable angina, or repeat revascularization. Specifically, patients who took a PPI faced a 70% increase in the risk of heart attack or unstable angina, a 48% increase in the risk of stroke or stroke-like symptoms, and a 35% increase in the need for a repeat coronary procedure. The study included 16,690 patients taking clopidogrel for a full year following coronary stenting.
- The study examined outcomes of patients taking pantoprazole (Protonix), esomeprazole (Nexium), omeprazole (Prilosec), and lansoprazole (Prevacid). It did not review outcomes in patients taking any of the newer PPIs, such as rabeprazole (Aciphex) or dexlansoprazole (Kapidex).
- Patients enrolled in the study took PPIs for an average of nine months.
- This is the largest trial to date to examine the outcomes of patients who are taking clopidogrel and a PPI.
- Two smaller, earlier studies examining adverse effects in patients taking both medications showed conflicting results. The first study, a database analysis, found an increase in cardiac events in patients taking clopidogrel and a PPI, while the CREDO study found no adverse effect when clopidogrel was taken with a PPI.
Take Away Message for Health Care Providers
The main take away from the data set is as follows: the overall event rate for the cohort without PPIs was 17.9% (a composite of risk of hospitalization for heart attack, stroke, unstable angina or repeat revascularization). The entire cohort taking the different PPIs had a 50% increase over the control group. The event rates for the individual PPIs are lansoprazole (Prevacid) 24.3%, esomeprazole (Nexium) 24.9%, omeprazole (Prilosec) 25.1% and pantoprazole (Protonix) 29.2%, all statistically significant compared to the no-PPI control group at 17.9%.
For patients who have received a stent, PPIs are often prescribed for a short duration following stenting to prevent gastrointestinal side effects of dual-antiplatelet therapy (nausea, dyspepsia). Some patients are also prescribed PPIs either before they undergo stenting or afterward, for indications unrelated to their dual antiplatelet therapy, such as peptic ulcer disease or gastrointestinal reflux. These patients may be taking a PPI for an extended period.
While more research is needed on this topic, SCAI urges health care providers who are treating post-stenting patients on dual-antiplatelet therapy to consider prescribing a histaminergic (H2) blocker (such as Zantac or Tagamet) or antacids instead of a PPI considering the high risk for adverse events shown in this study. H2 blockers are not metabolized by the CYP enzyme system that is responsible for activating the pro-drug, clopidogrel, into the active metabolite of clopidogrel that has antiplatelet actions. Therefore, there is no inhibition of the antiplatelet effect of clopidogrel by H2 blockers.
In cases in which the patient needs medication to treat gastrointestinal conditions unrelated to their cardiac disease or its treatment with a stent, the interventional cardiologist is advised to contact the patient’s primary care provider or gastroenterologist to discuss treatment alternatives to PPIs.