Proton-Pump Inhibitors Reduce GI Events in Low- and High-Dose Aspirin Therapy

Study Questions:

What is the safety and efficacy of proton-pump inhibitor (PPI) therapy in patients receiving dual antiplatelet therapy (DAPT) in low- and high-dose aspirin subsets?


This was a post hoc analysis of the COGENT (Clopidogrel and the Optimization of Gastrointestinal [GI] Events Trial) study. COGENT was a global, prospective, phase III, randomized, placebo-controlled, double-blind, double-dummy clinical trial of a fixed combination of clopidogrel 75 mg and omeprazole 20 mg compared with clopidogrel 75 mg alone. Daily enteric-coated aspirin was administered to all study patients in open-label fashion, but specific dosing was left to the treating clinician. Randomized patients with available aspirin dosing information were divided into “low-dose” (≤100 mg) and “high-dose” (>100 mg) aspirin groups. The primary GI and cardiovascular endpoints were composite upper GI events and major adverse cardiac events (MACE), respectively.


A total of 3,752 (99.8%) patients had available aspirin dosing information; 66.1% of patients received low-dose aspirin. Median follow-up was 110 days. High-dose aspirin was associated with similar 180-day Kaplan-Meier estimates of adjudicated composite GI events and MACE, compared with low-dose aspirin. Randomization to PPI therapy reduced 180-day Kaplan-Meier estimates of the primary GI endpoint in low-dose (1.2% vs. 3.1%; p = 0.003) and high-dose aspirin subsets (0.9% vs. 2.6%; p = 0.05), and did not affect the primary cardiovascular endpoint in either group. The corresponding number needed to treat estimated to prevent one major composite upper GI event with 6 months of PPI therapy was 52 in the low-dose aspirin subset and 58 in the high-dose aspirin subset.


Among patients receiving DAPT with clopidogrel and aspirin, PPI therapy reduced upper GI events in both low- and high-dose aspirin patient subsets without adversely affecting cardiovascular endpoints.


This is an important post hoc analysis of the COGENT trial. The findings offer continued reassurance that the potential interaction between PPIs and clopidogrel does not translate into adverse cardiovascular outcomes. Furthermore, the authors offer continued evidence that about one-third of patients on DAPT continue to receive high-dose aspirin. Last, the authors draw attention to the benefits of GI protection with PPI therapy in patients receiving even low-dose aspirin therapy. The merits of this approach of GI protection, do not, however, account for any of the consequences or side effects of prolonged PPI therapy. Nonetheless, a GI protective strategy may be beneficial in appropriately selected patients, including those on low-dose aspirin and especially those at escalated risk for upper GI events.

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