SPICE: Esomeprazole Reduces Antiplatelet Effect of Clopidogrel

SAN FRANCISCO, CA—Patients who have undergone percutaneous coronary intervention (PCI) may experience a decreased antiplatelet effect of clopidogrel if they are prescribed the proton pump inhibitor (PPI) esomeprazole, according to a randomized study presented November 9, 2011, at the annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium.

Previous trials have yielded conflicting results regarding the effects of both statins and PPIs on the antiplatelet activity of clopidogrel. Moreover, no previous randomized trials have addressed the impact of either rosuvastatin or esomeprazole, and there is very little data addressing whether CYP2C19*2 loss-of-function polymorphism status has an impact on the interaction of these 2 classes of drugs when given with clopidogrel.

For the SPICE (Evaluation of the influence of Statins and Proton-pump Inhibitors on Clopidogrel antiplatelet Effects) trial, Jean-Pierre Déry, MD, MSc, of Laval University School of Medicine (Quebec, Canada), and colleagues assigned 277 PCI patients to rosuvastatin (20 mg; n = 144) or atorvastatin (80 mg; n = 133). After CYP2C19*2 status was determined, patients received 80 mg aspirin and 75 mg maintenance clopidogrel.

At 30 days, platelet function testing was conducted using light transmittance aggregometry and vasodilator stimulated phosphoprotein (VASP). Maximal platelet aggregation > 46% and platelet reactivity index (PRI) > 50% were indicative of high on-treatment platelet reactivity.

The rosuvastatin and atorvastatin groups were further stratified by statin group and CYP2C19*2 genotype. They were then randomized to 1 of 4 gastroprotective agents:

• Esomeprazole
• Omeprazole
• Pantoprazole
• Ranitidine

Platelet function was assessed again at 60 days.

Statin Choice Not Critical

Baseline characteristics were similar between the atorvastatin and rosuvastatin arms, with the exception of a higher rate of previous CABG in the rosuvastatin group.

At 30 days, there were no effects of atorvastatin or rosuvastatin on the antiplatelet effects of clopidogrel. Of the gastroprotective agents, esomeprazole was associated with the greatest change in platelet reactivity as measured by both maximal platelet aggregation and PRI (figure 1).

On multivariate analysis, esomeprazole therapy (OR 2.9, 95% CI 1.1-7.7; P < 0.0001) and high platelet reactivity before PPI (OR 0.24, 95% CI 0.08-0.59; P < 0.0001) were independently associated with change in maximal platelet aggregation greater than 10%. Similarly, esomeprazole (OR 8.8, 95% CI 3.3-24.9; P < 0.0001), omeprazole (OR 3.0, 95% CI 1.2-8.1; P = 0.02) and high platelet reactivity before PPI therapy (OR 0.25 95% CI 0.12-0.52; P = 0.0002) were associated with change in PRI greater than 10%.

“Esomeprazole significantly reduces the antiplatelet effect of clopidogrel,” Dr. Déry said, adding that the PPI pantoprazole and the H2-receptor antagonist ranitidine have comparably small effects. In addition, rosuvastatin and atorvastatin have similar effects on clopidogrel’s platelet inhibition.

Source:

Déry JP. SPICE: A prospective, randomized trial of four antacid strategies in patients receiving clopidogrel. Presented at: Transcatheter Cardiovascular Therapeutics 2011; November 9, 2011; San Francisco, CA.

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