I would submit for starters that drug-drug interaction issues are one of the most vexing, often substantiated by competing claims rooted in plausible pharmacokinetic mechanisms. Nevertheless, each one of us has to find our own version of the truth.

Regarding this issue there unfortunately isn’t an absolute one. This realization manifests on how we practice and what we advise our patients. Well, then this blog should get all of you out there to respond with pithy comments on your take of the evidence presented so far publicly. Also, how justifiable is the position FDA has adopted? Another important question is, are most PPI prescriptions for patients on dual anti-platelet therapy (DAPT) justified?

One of the most publicized studies from Ho et al, published in JAMA 2009, reported PPI use in 64% clopidogrel treated patients post-acute coronary syndrome (ACS). Concomitant use of clopidogrel and a PPI was associated with a 25% greater risk of death or re-hospitalization for ACS, the primary end point. Interestingly, only 8% patients had a history of GI bleed and 25% had an in-hospital or after discharge bleed, making most PPI prescriptions empiric! The heavily confounded registry data from this and other similar studies is not supported by the evidence from randomized trials like COGENT-1.

However, in my view the availability of omeprazole (most frequently prescribed) over the counter (OTC) since 2006 raises an important public safety issue, and though the debate over the strength of the evidence behind the warning issued by FDA is legitimate, the justification for recommending caution is not. I support the FDA’s position in light of the fact that PPI are available OTC and the actual use of this drug along with clopidogrel may be grossly underestimated, and so the associated potential risk. The answer lies in selective and thoroughly justifiable use of PPI in patients on DAPT with clopidogrel. The recommendation for a PPI with clopidogrel is currently reserved for high-risk patients at an increased risk of bleeding. It may however be reasonable to avoid omeprazole, along with a commonsense recommendation of taking clopidogrel or a PPI at least a few hours apart to minimize the potential for any interaction.

Moreover, the extreme publicity and awareness about this interaction has just come ahead of Prasugrel launch and clopidogrel becoming generic. Is this a mere coincidence? Prasugrel and Ticagrelor (not yet approved) are devoid of this interaction; however does this imply that we use them routinely over generic clopidogrel? Are there any takers for the strategy of routine testing for the cytochrome-P450 reduction/loss of function genetic polymorphisms that could potentially predict a greater impact of a clopidogrel-PPI interaction and hence for selective use of Prasugrel or Ticagrelor.

We are currently engaged in evaluating one of the nation’s largest Veteran Affairs datasets regarding medication prescriptions, especially in patient’s post-coronary stent implantations. This is the group of patients for whom this interaction may hold the greatest risk of serious complications. These data would be presented at the upcoming national scientific meetings.

In conclusion, I believe in careful evaluation of each PPI prescription at the initial or follow-up visits and critical assessment of the need for a PPI prescription in patients on clopidogrel. I am eager to learn all your comments and suggestions.

Dr Subhash Banerjee is a board certified Interventional Cardiologist and Endovascular specialist. He is the Chief of cardiology at VA North Texas Health Care System and an Associate Professor of medicine UT Southwestern Medical Center in Dallas, Texas. Dr Banerjee serves as a national proctor, teaching physicians the techniques of endovascular therapy for coronary and peripheral interventions. Dr Banerjee leads an active clinical research program focused on anti-platelet therapy, DES, and peripheral interventions.