Patients with acute coronary problems are often given anti-clotting agents which carry a danger of gastro-intestinal bleeding. To alleviate this risk, a proton pump inhibitor may be prescribed, but a new study suggests that the anti-clotting agent clopidogrel may increase risk of re-hospitalization or even death.

 Summary

Prescription of clopidogrel and aspirin is common after acute heart problems requiring hospitalization. The drugs prevent clotting and further cardiac events but they also can cause stomach bleeding. Therefore, a proton pump inhibitor might be added to reduce this risk. A new study shows that the clopidogrel-proton pump inhibitor combination might pose some risks of its own.

Introduction

Following acute coronary syndrome (ACS) which includes unstable angina and heart attack, patients will often be prescribed aspirin or the antiplatelet drug clopidogrel to prevent further blood clots. However, anticlotting or antiplatelet medication can cause stomach bleeding and to offset this risk, a proton pump inhibitor (PPI) might be added. The PPIs reduce stomach acid and are commonly used in gastrointestinal problems. However, drugs can interact, to the detriment of the patient, and there have been some reports that PPIs can reduce the effectiveness of clopidogrel, which could therefore increase the risk of clotting again.

What was done

A comparison of outcomes for patients taking clopidogrel after ACS with and without PPIs has been carried out by researchers at Denver Medical Center. They recorded rates of all cause death and rehospitalization.

What was found

Of 8,205 patients prescribed clopidogrel after discharge from hospital for ACS, almost 64% were also taking a PPI. Death or rehospitalization occurred among 29.8% of those on clopidogrel and PPI and among 20.8% of those on clopidogrel alone. The researchers say that the use of clopidogrel and PPI at any time was linked to a 25% increase in the odds of death or rehospitalization compared to not taking a PPI.

What this study means

The researchers believe it is the interaction between clopidogrel and the PPI, rather than the PPI itself, which leads to the adverse outcomes seen with the combination. Therefore, PPIs should only be given with clopidogrel to those with a clear risk of gastrointestinal bleeding, rather than routinely. Other medications to protect the gastrointestinal tract might also be considered - more information about how these interact with clopidogrel is needed.

Source

Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome PM. Ho, TM. Maddox,  et al, Journal of the American Medical Association, March 4 2009, vol. 301, pp. 937--944