Key result
Alpha-1 antagonists like tamsulosin significantly reduced lower urinary tract symptoms in older adults (mean IPSS reduction of 8.86 points), while doxazosin was associated with an increased risk of cardiovascular events compared to chlorthalidone in hypertensive patients.
Why the study?
Alpha-1 antagonists are frequently used for LUTS/BPH and therapy-resistant hypertension in older adults, but a complete overview of benefits and risks in people 65 years and older was needed to derive safe prescribing recommendations.
Do adrenergic alpha-1 receptor antagonists improve symptoms and are they safe in older adults with LUTS or hypertension?
Meta-Analysis
Do adrenergic alpha-1 receptor antagonists improve symptoms and are they safe in older adults with LUTS or hypertension?
Doxazosin should not be used as a first-line antihypertensive due to increased heart failure risk, while alpha-1 antagonists for BPH effectively relieve symptoms but require careful consideration of adverse events like falls and hypotension in older adults.
Supports tamsulosin for LUTS in older adults; reinforces caution against doxazosin in hypertension due to higher CV event risk.
BackgroundAdrenergic alpha-1 receptor antagonists (alpha-1 antagonists) are frequently used medications in the management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and in the management of therapy-resistant arterial hypertension, two conditions frequently found in older adults. This systematic review aims at presenting a complete overview of evidence over the benefits and risks of alpha-1 antagonist treatment in people ≥ 65 years, and at deriving recommendations for a safe application of alpha-1 antagonists in older adults from the evidence found.MethodsA comprehensive literature search was performed including multiple databases (Medline/Pubmed, Embase, the Cochrane Library) and using the PICOS framework to define search terms. The selection of the studies was done by two independent reviewers in a two-step approach, followed by a systematic data extraction. Quality appraisal was performed for each study included using standardised appraisal tools. The studies retrieved and additional literature were used for the development of recommendations, which were rated for strength and quality according to the GRADE methodology. ResultsFourteen studies were included: 3 meta-analyses, 6 randomised controlled trials and 5 observational trials. Doxazosin in the management of arterial hypertension was associated with a higher risk of cardiovascular disease, particularly heart failure, than chlorthalidone. Regarding treatment of LUTS suggestive of BPH, alpha-1 antagonists appeared to be effective in the relief of urinary symptoms and improvement of quality of life. They seemed to be less effective in preventing disease progression. Analyses of the risk profile indicated an increase in vasodilation related adverse events and sexual adverse events for some agents. One large observational study points at an increased risk of falls and fractures. The effects of long-term treatment remained unclear. All meta-analyses and 5 out of 6 interventional studies were downgraded in the quality appraisal. 4 out of 5 observational studies were of good quality.ConclusionsIt cannot be recommended to use doxazosin as first-line antihypertensive agent neither in older adults nor in younger patients. In the management of BPH alpha-1 antagonists promise to effectively relieve urinary symptoms with uncertainty regarding their efficacy in preventing long-term progression events.
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Mansbart et al. (2022) conducted a meta-analysis in Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and arterial hypertension. Adrenergic alpha-1 receptor antagonists (e.g., tamsulosin, doxazosin) vs. Placebo, active comparator, or baseline was evaluated on Change in International Prostate Symptom Score (IPSS) for tamsulosin 0.2 mg (pre vs post administration) (MD -8.86, 95% CI -11.14 to -6.58). Alpha-1 antagonists like tamsulosin significantly reduced lower urinary tract symptoms in older adults (mean IPSS reduction of 8.86 points), while doxazosin was associated with an increased risk of cardiovascular events compared to chlorthalidone in hypertensive patients.
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