Cardiac failure may be associated with long term medical therapy of benign prostatic hyperplasia

Introduction and Objective — Worrisome reports of increased risk of cardiac failure with alpha blockers (ABs) in hypertension studies (alfuzosin in ALLHAT) and 5-alpha reductase inhibitors (5ARIs) in prostate studies (dutasteride in REDUCE) have raised safety concerns with these medications for long term management of Benign Prostatic Hyperplasia (BPH). The objective of this study was to determine if 5ARIs and/or ABs were associated with an increased risk of cardiac failure in males with BPH.

Methods — A retrospective cohort was created using the province of Ontario’s health administrative databased at the Institute for Clinical Evaluative Sciences (ICES). Males aged 66 and over with a standardized diagnosis of BPH were included. Subjects were categorized based on exposure to 5ARI and/or AB exposure. Further information collected included: standardized diagnosis of “new” cardiac failure, exposure time to 5ARIs and/or ABs, dosage, formulations, age, socioeconomic status and comorbidities associated with cardiac disease. Subjects with a history of cardiac failure or prostate cancer were excluded. A competing risk model was used to determine if 5ARI and/or AB use was associated with an increased risk of cardiac failure.

Results — From January 1st 2005 to December 31st 2015, 175,201 BPH subjects (aged 66 and older) were included in the analysis: 69,988 with no treatment, and 8,339, 55,383, and 41,491 exposed to 5ARI, AB and combination therapy respectively (there was no significant difference in study demographic parameters between groups). The competing risk model comparing exposed subjects to those with no treatment, showed that subjects with BPH treated with 5ARI and AB, alone or in combination had a statistically increased risk of being diagnosed with cardiac failure. Cardiac failure risk was highest for ABs alone (HR 1.260; 95% CI 1.218-1.304, p<0.001), intermediate for combination ABs/5ARIs (HR 1.151; 95% CI 1.110-1.194, p<0.001) and lowest for 5ARIs alone (HR 1.074; 95% CI 1.003-1.151, p=0.0412).

Conclusions — This large, long term retrospective analysis of men with BPH found a statistically significant increase in “new” cardiac failure in men exposed to both 5ARI and AB therapy with the highest risk for men exposed to AB (alone or in combination with 5ARI).