Proton pump inhibitors (PPIs) may reduce the benefits of aspirin in patients with coronary artery disease (CAD)

Proton pump inhibitors (PPIs) may reduce the benefits of aspirin in patients with coronary artery disease (CAD), researchers from Denmark report.

Previous research has suggested that concomitant PPI use might be responsible for the reduced aspirin efficacy seen in some patients.

“Aspirin is the mainstay of secondary antithrombotic treatment; accordingly, low-dose aspirin lowers the risk of vascular events by 32% in high-risk patients,” explain Anne-Mette Hvas (Aarhus University Hospital, Brendstrupgaardsvej) and colleagues in the journal Heart.

“However, platelet response to aspirin is variable and in some patients platelet aggregation is inhibited less than expected and these patients might be at an increased risk of cardiovascular events.”

PPIs exert their antacid effect by inhibiting an ATPase associated with gastric parietal cells and raising intragastric pH, which can greatly reduce the lipophilicity of aspirin and, therefore, potentially its efficacy.

To better understand the effects of PPIs on aspirin function, the investigators studied 418 patients with stable CAD, all of whom were taking aspirin 75 mg/day and 54 of whom were also taking PPIs.

Analysis revealed that platelet aggregation was significantly greater in patients taking aspirin as well as a PPI (180 units/min) than in those taking aspirin only (152 units/min).

Platelet activation, as assessed by levels of soluble serum P-selectin, was also significantly increased in those taking both aspirin and a PPI (88.5 ng/ml) than those taking aspirin only (75.4 ng/ml).

Importantly, these differences were not explained by differences in age, sex, body mass index, blood pressure, family history of ischemic heart disease, smoking, or diabetes, all of which factors were well balanced between patient groups.

Although the authors did not demonstrate a causal link between PPI use and reduced aspirin function, “these findings may nevertheless affect the clinical practice of antithrombotic treatment,” conclude the researchers.

“In view of the widespread use of PPIs, a randomised double-blind crossover study is needed to explore further the inhibitory effect of PPIs on aspirin,” the investigators recommend.