, Volume 28, Issue 2, pp 223-230

Confounding in the Association of Proton Pump Inhibitor Use With Risk of Community-Acquired Pneumonia

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ABSTRACT

BACKGROUND

Use of proton pump inhibitors (PPIs) is associated with community-acquired pneumonia (CAP), an association which may be confounded by unobserved patient and prescriber characteristics.

OBJECTIVE

We assessed for confounding in the association between PPI use and CAP by using a ‘falsification approach,’ which estimated whether PPI use is also implausibly associated with other common medical conditions for which no known pathophysiologic link exists.

DESIGN

Retrospective claims-based cohort study.

SETTING

Six private U.S. health plans.

SUBJECTS

Individuals who filled at least one prescription for a PPI (N = 26,436) and those who never did (N = 28,054) over 11 years.

INTERVENTIONS

Multivariate linear regression of the association between a filled prescription for a PPI and a diagnosis of CAP in each 3-month quarter. In falsification analyses, we tested for implausible associations between PPI use in each quarter and rates of osteoarthritis, chest pain, urinary tract infection (UTI), deep venous thrombosis (DVT), skin infection, and rheumatoid arthritis. Independent variables included an indicator for whether a prescription for a PPI was filled in a given quarter, and quarterly indicators for various co-morbidities, age, income, geographic location, and marital status.

KEY RESULTS

Compared to nonusers, those ever using a PPI had higher adjusted rates of CAP in quarters in which no prescription was filled (68 vs. 61 cases per 10,000 persons, p < 0.001). Similar associations were noted for all conditions (e.g. chest pain, 336 vs. 282 cases, p < 0.001; UTI, 151 vs. 139 cases, p < 0.001). Among those ever using a PPI, quarters in which a prescription was filled were associated with higher adjusted rates of CAP (111 vs. 68 cases per 10,000, p < 0.001) and all other conditions (e.g. chest pain, 597 vs. 336 cases, p < 0.001; UTI, 186 vs. 151 cases, p < 0.001), compared to quarters in which no prescription was filled.

CONCLUSION

PPI use is associated with CAP, but also implausibly associated with common medical conditions. Observed associations between PPI use and CAP may be confounded.