Stent patients who take Sanofi-Aventis/Bristol-Myers Squibb’s bloodthinner blockbuster Plavix with proton pump inhibitors such as AstraZeneca’s Prilosec and Nexium or Wyeth’s Protonix face an increased risk of serious cardiovascular events.

This is the claim of a study funded by the USA’s pharmacy benefit manager Medco Health Solutions and presented at the American Heart Association meeting in New Orleans. Researchers tracked 16,690 patients who had undergone a percutaneous coronary intervention such as stent placement or balloon angioplasty, and had started taken Plavix (clopidogrel) as maintenance therapy; 9,862 patients were taking clopidogrel alone and 6,828 were on Plavix and a PPI and were tracked for a year, using medical and pharmacy claims data.

Medco describes the results as “striking”, noting that the relative risk of a major adverse cardiovascular event was 50% higher, and the risk of a heart attack specifically was 74% higher, in patients taking both medications together. The incidence of a major cardiovascular event within 12 months of starting clopidogrel was 25% for patients taking both medications concurrently.

Plavix is the second best-selling drug in the world after Pfizer’s Lipitor (atorvastatin), with global sales of $7.3 billion in 2007, while combined Nexium (esomeprazole) and Prilosec (omeprazole) sales were not far behind, at over $6.4 billion

The researchers claimed that since PPIs mimic the effect of a variant gene, which also renders Plavix ineffective, this study further suggests a potential role for genetic testing. Robert Epstein, lead study author and chief medical officer at Medco, said that “considering the widespread use of these two medications, this important research adds to a growing body of evidence raising questions about their concurrent use and suggests further research is needed".

He added that “with this research in hand, we intend to open a dialogue with the major clinical organisations to advance the discussion around the guidelines that govern the use of Plavix." Medco said it will pass the findings onto the US Food and Drug Administration as part of their recently-announced pharmacogenomics collaboration.

AstraZeneca, which markets Nexium and Prilosec said its ongoing monitoring programme, plus a comprehensive review of clinical trial data and reports from marketed use, have not raised safety concerns to date on the use of its products in conjunction with Plavix. B-MS noted that the safety and efficacy of its drug have been established in trials including over 100,000 patients.

Other observers have questioned the approach adopted by Medco and questioned the concept of retrospective analyses as opposed to rigourous clinical data.