Tamsulosin treatment for benign prostatic hyperplasia and risk of severe hypotension in men aged 40-85 years in the United States: risk window analyses using between and within patient methodology
BMJ 2013; 347 doi: https://doi.org/10.1136/bmj.f6320 (Published 05 November 2013) Cite this as: BMJ 2013;347:f6320
- Steven T Bird, lead epidemiologist12,
- Joseph A C Delaney, research assistant professor3,
- James M Brophy, professor4,
- Mahyar Etminan, assistant professor5,
- Sean C Skeldon, resident67,
- Abraham G Hartzema, professor2
- 1Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Department of Epidemiology, Silver Spring, MD, USA
- 2University of Florida, College of Pharmacy and Epidemiology, Pharmaceutical Outcomes and Policy, Gainesville FL, USA
- 3University of Washington, School of Public Health, Department of Epidemiology, Seattle, WA, USA
- 4McGill University Health Centre, Royal Victoria Hospital, Montreal, Quebec, Canada
- 5University of British Columbia, Therapeutic Evaluation Unit, Provincial Health Services Authority, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada V5Z1M9
- 6University of Toronto, Division of Urology, Department of Surgery, Toronto, Canada
- 7University of British Columbia, Department of Urologic Sciences, Vancouver, Canada
- Correspondence to: M Etminan metminan{at}popi.ubc.ca
- Accepted 29 September 2013
Abstract
Objective To characterize risk of hypotension requiring admission to hospital in middle aged and older men treated with tamsulosin for benign prostatic hyperplasia.
Design Population based retrospective cohort study (between patient methodology) and self controlled case series (within patient methodology).
Setting Healthcare claims data from the IMS Lifelink database in the United States.
Participants Men aged 40-85 years with private US healthcare insurance entering the cohort at their first dispensing for tamsulosin or for a 5α reductase inhibitor (5ARI) between January 2001 and June 2011after a minimum of six months’ enrolment.
Main outcomes measures Hypotension requiring admission to hospital. Cox proportional hazards models estimated rate ratios at time varying intervals during follow-up: weeks 1-4, 5-8, and 9-12 after tamsulosin initiation; weeks 1-4, 5-8, and 9-12 after restarting tamsulosin (after a four week gap); and maintenance tamsulosin treatment (remaining exposed person time). Covariates included age, calendar year, demographics, antihypertensive use, healthcare use, and a Charlson comorbidity score. A self controlled case series, having implicit control for time invariant covariates, was additionally conducted.
Results Among 383 567 new users of study drugs (tamsulosin 297 596; 5ARI 85 971), 2562 admissions to hospital for severe hypotension were identified. The incidence for hypotension was higher for tamsulosin (42.4 events per 10 000 person years) than for 5ARIs (31.3 events per 10 000 person years) or all accrued person time (29.1 events per 10 000 person years). After tamsulosin initiation, the cohort analysis identified an increased rate of hypotension during weeks 1-4 (rate ratio 2.12 (95% confidence interval 1.29 to 3.04)) and 5-8 (1.51 (1.04 to 2.18)), and no significant increase at weeks 9-12. The rate ratio for hypotension also increased at weeks 1-4 (1.84 (1.46 to 2.33)) and 5-8 (1.85 (1.45 to 2.36)) after restarting tamsulosin, as did maintenance tamsulosin treatment (1.19 (1.07 to 1.32)). The self controlled case series gave similar results as the cohort analysis.
Conclusions We observed a temporal association between tamsulosin use for benign prostatic hyperplasia and severe hypotension during the first eight weeks after initiating treatment and the first eight weeks after restarting treatment. This association suggests that physicians should focus on improving counseling strategies to warn patients regarding the “first dose phenomenon” with tamsulosin.
Footnotes
This study represents the opinions of the authors and not those of the Food and Drug Administration.
Contributors: All authors took part in the study design and the analysis and interpretation of the data. The manuscript was drafted by STB and critically revised for important intellectual content by all authors. STB had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors approved the final manuscript for publication. AGH is the study guarantor.
Funding: This work was funded in part by the McGill University Health Center, Fonds de la Recherche en Santé du Québec, and the Ministère de la Santé et des Services Sociaux. The authors had full autonomy in the study design; the collection, analysis, and interpretation of data; the writing of the article; and the decision to submit it for publication. The authors have no other conflicts or competing interests to declare.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the McGill University Health Center, Fonds de la Recherche en Santé du Québec, and the Ministère de la Santé et des Services Sociaux for the submitted work; JMB has received peer review financial support from le Fonds de la Recherche en Santé du Québec, JACD has a research grant from the Agency for Healthcare Research and Quality, AGH is a principal investigator for the Observational Medical Outcomes Partnership, a private-public partnership designed to help improve drug safety monitoring, and STB is employed by the US Food and Drug Administration; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: This study was approved by the University of Florida institutional review board (180-2012).
Data sharing: Based on our third party access agreement for the data with IMS and IRB restrictions, no additional data available.
STB affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.
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