NEW ORLEANS, LA—The effect of a fixed-dose combination of naproxen and esomeprazole on cyclooxygenase-1 (COX-1) inhibition by low-dose aspirin was found to be noninferior to low-dose aspirin alone in healthy subjects, according to the results of a Phase 1 study presented today at ACC.11, the American College of Cardiology’s 60th Annual Scientific Session.
Patients with arthritis who are also at cardiovascular risk may use concomitant low-dose aspirin and nonsteroidal antiinflammatory drugs (NSAIDs). Evidence suggests that NSAIDs may interfere with low-dose aspirin platelet inhibition. To determine the effect of a fixed-dose combination of enteric-coated naproxen 500mg and immediate-release esomeprazole magnesium 20mg on the antiplatelet action of low-dose aspirin, Catherine Datto MD, and colleagues from the University of Florida College of Medicine in Jacksonville, conducted a Phase 1, single-center, double-blind, placebo-controlled, parallel-group study.
In this study, healthy adults aged 50–75 years received enteric-coated low-dose aspirin 81mg once daily on Days 1 to 5 and then subsequently were randomized to receive low-dose aspirin plus either naproxen/esomeprazole magnesium or placebo twice daily on Days 6 to 10. Levels of serum thromboxane B2 (TXB2), a specific marker of low-dose aspirin-induced effects on platelet COX-1 activity, were assessed on Days 1 and 6 (predose), and on Day 11, the investigators said.
Primary endpoint was percentage of TXB2 inhibition from Day 1 to Day 11. The primary analysis included subjects with ≥95% TXB2 inhibition at Day 6 vs. Day 1 and TXB2 data at day 11. Noninferiority was concluded if the lower limit of 90% confidence interval (CI) in percent inhibition exceeded 90%.
A total of 42 subjects were enrolled and 40 randomized with a mean age of 60±7 years; 32 were evaluable, 14 in the group treated with low-dose aspirin + naproxen/esomeprazole magnesium and 18 in the group treated with low-dose aspirin + placebo.
In the low-dose aspirin + naproxen/esomeprazole magnesium group, mean TXB2 concentration was 10127.6pg/mL at Day 1, 38.5pg/mL at Day 6, and 15.1pg/mL at Day 11; in the low-dose aspirin + placebo group, this concentration was 5644.9pg/mL, 21pg/mL, and 13.3pg/mL on Days1, 6, and 11, respectively.
Mean percent TXB2 inhibition from Day 1 to Day 6 in the low-dose aspirin + naproxen/esomeprazole magnesium group was 99.2% (90% CI 0.8; 98.8–99.6) and, in the low-dose aspirin + placebo group, 98.8% (90% CI 1.3; 98.2–99.3). The 90% CI lower limits around percent TXB2 inhibition from Day 1 to Day 11 exceeded 90% for both groups: 99.6% (90% CI 0.5; 99.4–99.8) for the low-dose aspirin + naproxen/esomeprazole magnesium group and 99.1% (90% CI 1.1; 98.7–99.6) for the low-dose aspirin + placebo group.