The risk of fall and fracture with the initiation of a prostate-selective α antagonist: a population based cohort study.
OBJECTIVE
Do men starting treatment with prostate-specific α antagonists have increased risk of fall and fracture?


METHODS
Administrative datasets from the province of Ontario, Canada, that contain patient level data were used to generate a cohort of 147,084 men aged ≥ 66 years who filled their first outpatient prescription for prostate-specific α antagonists tamsulosin, alfuzosin, or silodosin between June 2003 and December 2013 (exposed men) plus an equal sized cohort matched 1:1 (using a propensity score model) who did not initiate α antagonist therapy. The primary outcome was a hospital emergency room visit or inpatient admission for a fall or fracture in the 90 days after exposure.


CONCLUSIONS
The men exposed to prostate-specific α antagonist had significantly increased risks of falling (odds ratio 1.14 (95% CI 1.07 to 1.21), absolute risk increase 0.17% (0.08 to 0.25%)) and of sustaining a fracture (odds ratio 1.16 (1.04 to 1.29), absolute risk increase 0.06% (0.02 to 0.11%)) compared with the unexposed cohort. This increased risk was not observed in the period before α antagonist use. Secondary outcomes of hypotension and head trauma were also significantly increased in the exposed cohort (odds ratios 1.80 (1.59 to 2.03) and 1.15 (1.04 to 1.27) respectively). The two cohorts were similar across 98 different covariates including demographics, comorbid conditions, medication use, healthcare use, and prior medical investigation. Potential unmeasured confounders, such as physical deconditioning, mobility impairment, and situational risk factors, may exist. The data used to identify the primary outcomes had limited sensitivity, so the absolute risks of the outcomes are probably underestimates. The study only included men ≥ 66 years old, and 84% of exposed men were prescribed tamsulosin, so results may not be generalizable to younger men, and there may not be statistical power to show small differences in outcomes between the drugs.


CONCLUSIONS
Prostate-specific α antagonists are associated with a small but significant increased risk of fall, fracture, and head trauma, probably as a result of induced hypotension.


BACKGROUND
This project was conducted at the Institute for Clinical Evaluative Sciences (ICES) Western Site through the Kidney, Dialysis, and Transplantation (KDT) research program. BW has received a research grant from Astellas, and L-AF does consultancy for Amgen.
Department of Surgery, Western University, London ON N6A 4V2, Ontario, Canada Institute for Clinical Evaluative Sciences, London, Ontario Department of Epidemiology and Biostatistics, Western University, London, Ontario bkwelk@gmail.com.
Blayne
B
Welk
Institute for Clinical Evaluative Sciences, London, Ontario.
Eric
E
McArthur
Department of Medicine, Western University, London, Ontario.
Lisa-Ann
LA
Fraser
Institute for Clinical Evaluative Sciences, London, Ontario.
Jade
J
Hayward
Institute for Clinical Evaluative Sciences, London, Ontario Department of Epidemiology and Biostatistics, Western University, London, Ontario.
Stephanie
S
Dixon
Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Y Joseph
YJ
Hwang
Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario.
Michael
M
Ordon
D000058:Accidental Falls / Q000517:prevention & control / Q000706:statistics & numerical data; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D000368:Aged; D002170:Canada / Q000453:epidemiology; D006259:Craniocerebral Trauma / Q000453:epidemiology / Q000209:etiology; D050723:Fractures, Bone / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D007022:Hypotension / Q000139:chemically induced / Q000150:complications; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D017063:Outcome Assessment, Health Care; D011467:Prostate; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects; D000077409:Tamsulosin
D058668:Adrenergic alpha-1 Receptor Antagonists; D007211:Indoles; D011799:Quinazolines; D013449:Sulfonamides; C047638:alfuzosin; C095285:silodosin; D000077409:Tamsulosin