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A3262 - Incident Diuretic Drug Use and Adverse Respiratory Events Among Older Adults with COPD
Author Block: N. Vozoris1, X. Wang2, P. Austin3, D. E. O'Donnell4, S. D. Aaron5, T. M. To6, A. S. Gershon7; 1Medicine, University of Toronto, Toronto, ON, Canada, 2Institute for Clinical Evaluative Sciences, Toronto, ON, Canada, 3Insitute for Clinical Evaluative Sciences, Toronto, ON, Canada, 4Kingston General Hosp, Kingston, ON, Canada, 5The Ottawa Hosp, Ottawa, ON, Canada, 6Hosp for Sick Children, Toronto, ON, Canada, 7Inst for Clinical Evaluative Sciences, Toronto, ON, Canada.
Rationale: Diuretic drugs may theoretically improve respiratory health outcomes in chronic obstructive pulmonary disease (COPD) through several possible mechanisms: by decreasing preload to the heart (which may in turn decrease pulmonary hypertension and cor pulmonale); by decreasing pulmonary edema; and, one specific diuretic drug, acetazolamide, has known respiratory stimulant properties. However, diuretic drugs may also lead to respiratory harm in COPD by inducing metabolic alkalosis, which may result in carbon dioxide retention, and by inducing hypokalemia, which may lead to respiratory muscle weakness and respiratory failure. There is minimal and conflicting data regarding the potential respiratory effects of diuretic drugs among individuals with COPD, with few previous studies focusing on systemic formulation diuretics and clinically-important respiratory health outcomes We evaluated the association of incident oral diuretic drug use with respiratory-related morbidity and mortality among older adults with COPD. Methods: This was a population-based, retrospective cohort study using health administrative data from Ontario, Canada, for the period 2008-2013. We identified adults aged 66 years and older with non-palliative COPD using a validated algorithm. Respiratory-related morbidity and mortality were evaluated within 30 days of incident oral diuretic drug use compared to non-use using Cox proportional hazard regression and applying inverse probability of treatment weighting using the propensity score to minimize confounding. Results: Out of 99,766 individuals aged 66 years and older with COPD identified, incident diuretic receipt occurred in 51.7%. Relative to controls, incident diuretic users had significantly increased rates for hospitalization for COPD or pneumonia (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.07-1.40), as well as greater emergency room visits for COPD or pneumonia (HR 1.35, 95% CI 1.18-1.56), COPD or pneumonia-related mortality (HR 1.41; 95% CI 1.04-1.92) and all-cause mortality (HR 1.20, 95% CI 1.06-1.35). The increased respiratory-related morbidity and mortality observed was specifically as a result of loop diuretic use. Our overall findings are strengthened by the fact that we found negative respiratory outcomes with diuretic use even in healthier subgroups of individuals with COPD (such as those without history of respiratory exacerbation and those without pre-existing congestive heart failure) and when the comparison group was new drug use with a similar prescribing indication (i.e., angiotensin converting enzyme inhibitor/angiotensin receptor blocker use). Conclusions: Our large, population-based cohort study showed the novel finding that incident diuretic drug use (particularly use of loop diuretics) among older adults with non-palliative COPD is associated with increased rates of respiratory-related morbidity and mortality.