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

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 2011 after 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.

Conflict of interest statement

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.

Figures

Fig 1 Study cohort development

Fig 2 Person time allocation for drug exposure covariates. Schematic shows an example characterization of person time into exposure covariates for a given patient. Included person time starts at initiation of drug treatment and ends when healthcare eligibility finishes. The patient in this schematic contributes person time to three new use covariates, maintenance use, and two restarting exposure covariates. Dotted regions=actual exposed person time; diagonal line regions=attribution of person time to exposure covariates; vertical black lines=enrolment eligibility; vertical grey lines=exposure assessment; horizontal black lines=differentiates between depiction of exposure covariates along longitudinal patient time