Proton-Pump Inhibitor Therapy Effective Even With Low-Dose Aspirin in Coronary Artery Disease

pills, aspirin
pills, aspirin
Researchers used data from the COGENT trial to test proton-pump inhibitor therapy in patients taking low- and high-dose aspirin.

Gastroprotection with proton-pump inhibitor (PPI) therapy can be used appropriately in patients with coronary artery disease (CAD) requiring dual antiplatelet therapy (DAPT), even if they take low-dose aspirin, according to data published in the Journal of the American College of Cardiology.

The COGENT trial (Clopidogrel and the Optimization of Gastrointestinal Events Trial) showed that PPIs safely reduce rates of gastrointestinal (GI) events for patients requiring DAPT, although appropriate use of prophylactic PPI is suboptimal.

Researchers used data from the trial to investigate the safety and efficacy of PPI therapy in patients receiving DAPT in low- and high-dose aspirin groups.

“COGENT represented an ideal setting to examine optimal gastroprotection approaches by aspirin dosing given that the trial: 1) represented the only large, randomized placebo-controlled experience examining PPI use in this setting; 2) included robust global participation, potentially capturing regional variation in aspirin dosing; and 3) specifically adjudicated GI and cardiovascular events,” the authors wrote.

A total of 3752 patients from the COGENT trial were divided into low- (≤100 mg) and high-dose (>100 mg) aspirin groups. The primary GI end point was composite upper GI events, and the primary cardiovascular end point was any major adverse cardiac event.

Patients were followed for a median duration of 110 days. Those who took low-dose aspirin (n=2480) were more likely older, female, and had higher rates of peripheral artery disease, stroke, and hypertension. Whereas, those who took high-dose aspirin (n=1272) had higher rates of hyperlipidemia, more likely had smoked, and more likely had history of percutaneous coronary interventions.

Patients taking high-dose aspirin had similar Kaplan-Meier estimates  of adjudicated GI events at 180 days as those taking low-dose aspirin (1.7% vs 2.1%; adjusted hazard ratio [HR]: 0.88; 95% confidence interval [CI]: 0.46-1.66) as well as major adverse cardiac events (4.8% vs 5.5%; adjusted HR: 0.73; 95% CI: 0.48-1.11).

Randomization to PPI therapy reduced Kaplan-Meier estimated events at 180 days of GI events among patients taking low-dose (1.2% vs 3.1%; P=.003) and high-dose aspirin (0.9% vs 2.6%; P=.05). To prevent 1 major composite upper GI event, the corresponding needed-to-treat estimated was 52 in the low-dose aspirin group and 58 in the high-dose group. PPI therapy did not adversely affect cardiovascular events for either group (low-dose=5.6% vs 5.5%; P=.95; high-dose=4.2% vs 5.5%; P=.92).

However, it should be noted that the COGENT trial was not specifically powered to detect differences in safety and efficacy of PPI therapy by aspirin dosing. “Comparisons of clinical outcomes between different aspirin dosing regimens were nonrandomized and thus may be subject to residual confounding by indication,” researchers wrote. “The point estimates for GI and cardiovascular risks by aspirin dosing should be interpreted with caution, given the wide CIs.”

They concluded that more investigation is necessary to evaluate GI bleeding risks and the effectiveness of protective strategies that use alternative drug combinations with DAPT.


Vaduganathan M, Bhatt DL, Cryer BL, et al. Gastrointestinal events regardless of aspirin dose in patients requiring dual antiplatelet therapy. J Am Coll Cardiol. 2016; doi: 10.1016/j.jacc.2015.12.068.