Polypharmacy Increases Risk of Dyspnea Among Adults With Serious, Life-Limiting Diseases

Polypharmacy is associated with dyspnea in cross-sectional studies, but associations have not been determined in longitudinal analyses. Statins are commonly prescribed but their contribution to dyspnea is unknown. We determined whether polypharmacy was associated with dyspnea trajectory over time in adults with advanced illness enrolled in a statin discontinuation trial, overall, and in models stratified by statin discontinuation.

Using data from a parallel-group unblinded pragmatic clinical trial (patients on statins ≥3 months with life expectancy of 1 month to 1 year, enrolled in the parent study between June 3, 2011, and May 2, 2013, n = 308/381 [81%]), we restricted analyses to patients with available baseline medication count and ≥1 dyspnea score. Polypharmacy was assessed by self-reported chronic medication count. Dyspnea trajectory group, our primary outcome, was determined over 24 weeks using the Edmonton Symptom Assessment System.

The mean age of the patients was 73.8 years (standard deviation [SD]: ±11.0) and the mean medication count was 11.6 (SD: ±5.0). We identified 3 dyspnea trajectory groups: none (n = 108), mild (n = 130), and moderate-severe (n = 70). Statins were discontinued in 51.8%, 48.5%, and 42.9% of patients, respectively. In multivariable models adjusting for age, sex, diagnosis, and statin discontinuation, each additional medication was associated with 8% (odds ratio [OR] = 1.08 [1.01-1.14]) and 16% (OR = 1.16 [1.08-1.25]) increased risk for mild and moderate-severe dyspnea, respectively. In stratified models, polypharmacy was associated with dyspnea in the statin continuation group only (mild OR = 1.12 [1.01-1.24], moderate-severe OR = 1.24 [1.11-1.39]) versus statin discontinuation (mild OR = 1.03 [0.95-1.12], and moderate-severe OR = 1.09 [0.98-1.22]).

Polypharmacy was strongly associated with dyspnea. Prospective interventions to decrease polypharmacy may impact dyspnea symptoms, especially for statins.