Effect of Proton Pump Inhibitors on Risks of Upper and Lower Gastrointestinal Bleeding among Users of Low-Dose Aspirin: A Population-Based Observational Study.

Luis A. García Rodríguez,Angel Lanas,Lucía Cea Soriano,Pareen Vora,Montse Soriano-Gabarró

doi:10.3390/jcm9040928

Abstract

Estimates of the effect of proton pump inhibitors (PPIs) on risks of upper and lower gastrointestinal bleeding (UGIB and LGIB) among low-dose aspirin users in routine clinical practice are variable (UGIB) or lacking (LGIB). We aimed to establish these risks in the same observational study population. Using UK primary care data, we followed 199,049 new users of low-dose aspirin (75–300 mg/day) and matched non-users at start of follow-up to identify incident UGIB/LGIB cases. In nested case–control analyses, adjusted odds ratios (ORs) were calculated for concomitant PPI use vs. past (discontinued) PPI use among current low-dose aspirin users. For UGIB (n = 987), ORs (95% CIs) were 0.69 (0.54–0.88) for >1 month PPI use and 2.65 (1.62–4.3) for ≤1 month PPI use. Among the latter group, ORs (95% CIs) were 3.05 (1.75–5.33) for PPI initiation after start of aspirin therapy, and 1.66 (0.63–4.36) for PPI initiation on/before start of aspirin therapy. For LGIB (n = 1428), ORs (95% CIs) were 0.98 (0.81–1.17) for >1 month PPI use and 1.12 (0.73–1.71) for ≤1 month PPI use. Among low-dose aspirin users, maintaining PPI use (>1 month) was associated with a significantly reduced UGIB risk. Neither short nor long-term PPI use affected LGIB risk.

Highlights

Low-dose aspirin is widely prescribed for the secondary prevention of cardiovascular disease (CVD) as this benefit is well established in outweighing the risk of major bleeding [1]
The main characteristics of upper gastrointestinal bleeding (UGIB)/lower gastrointestinal bleeding (LGIB) cases and controls are shown in Table 1; further characteristics can be found in Supplementary Table S1)
Interpreting the true effect of short-term pump inhibitors (PPIs) use is challenging in a non-randomized setting, results of our analyses separating out the timing of PPI initiation will help to elucidate the likely true effects of PPI co-prescription among low-dose aspirin users that are otherwise difficult to infer in observational studies when PPI use is grouped as single category

Summary

Introduction

Low-dose aspirin is widely prescribed for the secondary prevention of cardiovascular disease (CVD) as this benefit is well established in outweighing the risk of major bleeding [1]. The net value of low-dose aspirin among individuals without CVD is less certain because of concerns about the risks of major bleeding [1,2], the most common being that in the gastrointestinal tract. Decisions to prescribe low-dose aspirin to this patient population in clinical practice, requires a careful assessment of individual bleeding risks. Small clinical studies have shown that PPIs contribute to injury in the small bowel among low-dose aspirin users [15,16] yet whether this translates into a higher risk of lower gastrointestinal bleeding (LGIB) is unclear, as findings from the limited observational data on this topic have been mixed [5,17]

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