ACC 2013: New systematic review highlights conflicting evidence between randomized trials and observational studies

March 10, 2013 – Researchers hoped to provide a clear recommendation to keep the existing FDA warning in place or modify it, but there was no clear consensus about what is best for patients.

Although the U.S. Food and Drug Administration (FDA) has issued a warning about a potential reduction in the anti-clotting effect of clopidogrel when taken in conjunction with a proton pump inhibitor (PPI, such as Prilosec), studies offer conflicting evidence. Some studies have indicated that taking a PPI with dual antiplatelet therapy (clopidogrel and aspirin) does not affect patient outcomes, whereas other studies have indicated an increased risk of heart attacks, strokes, and other serious complications.

In a new systemic review presented at the American College of Cardiology Scientific Sessions in San Francisco, CA, researchers analyzed all relevant studies to assess the safety and effectiveness of dual antiplatelet therapy combined with a PPI. They hoped to provide a clear recommendation to keep the existing FDA warning in place or modify it, but there was no clear consensus about what is best for patients. Lead author Chiara Melloni, MD, presented the results.

When patients with coronary artery disease are prescribed a regimen of clopidogrel and aspirin to prevent blood clots, it is common for clinicians to also prescribe a PPI. Antiplatelet medications increase the risk of bleeding, and PPIs are used to lower the risk of upper gastrointestinal bleeding and to protect the gastrointestinal tract.

For the systematic review, researchers identified 32 studies conducted between 1995 and 2012, assessed the quality of each study, and graded the strength of the evidence. Only four of the studies were randomized clinical trials; the rest were observational studies. The sample sizes in the randomized trials were small. The largest of the randomized trials was stopped before it reached its target enrollment of 5000 patients, so the trial suffers from the potential of being underpowered for events. The observational studies found that the use of PPIs were associated with worse clinical outcomes, but the randomized trials showed no significant difference in the rate of events for patients who received Prilosec compared with placebo.

“With 32 studies done to date and we can’t draw a strong conclusion about the safety and effectiveness of combining PPIs with dual antiplatelet therapy, we clearly still have work to do in this area,” said Dr. Melloni. “We are going to continue to analyze the data we compiled to see if we can learn more, but we believe more randomized trials are warranted in this area. For now, I would be selective when prescribing PPIs with dual antiplatelet therapy, and only recommend PPIs for patients with a higher risk of bleeding complications.”

Other DCRI researchers involved with the review included Schuyler Jones, MD; Sharif Halim, MD; Stephanie Mayer, MD; Brooke Heidenfelder; and Rowena Dolor, MD, who was the senior author.