A Meta-Analysis on the Efficacy and Tolerability of α1-Adrenoceptor Antagonists in Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Obstruction

Abstract

Objective: To assess whether the α₁-adrenoceptor antagonists currently available for the treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) (alfuzosin, terazosin, doxazosin and tamsulosin) can be distinguished with regard to clinical efficacy and/or tolerability. Methods: Up-to-date analysis of clinical placebo-controlled or direct comparative studies with α₁-adrenoceptor antagonists in patients with LUTS suggestive of BPO derived from a MEDLINE search in October 1998. All retrieved studies were analyzed with regard to efficacy and tolerability. Efficacy was evaluated by the percentage improvement in total symptom score and Q_max (mean end of study value relative to mean baseline value). Tolerability was evaluated by means of study withdrawal rate because of adverse events and the incidence of vasodilatatory adverse events (e.g. dizziness and orthostatic hypotension). Results: Indirect comparison of data derived from the placebo-controlled studies involving 6,333 patients and the data derived from the direct comparative studies involving 507 patients demonstrate that all α₁-adrenoceptor antagonists (alfuzosin, terazosin, doxazosin and tamsulosin) produce comparable improvements in LUTS and urinary flow. Total symptom score is in general improved by 30–40% and Q_max by 16–25%. The difference between currently available α₁-adrenoceptor antagonists is related to their side effect profile. Alfuzosin (especially the sustained release formulation) and tamsulosin (modified release formulation 0.4 mg) seem to be better tolerated than terazosin and doxazosin. The percentage of patients that withdrew due to bothersome side effects with alfuzosin and tamsulosin 0.4 mg was comparable to that with placebo (about 4–10%) whereas in the terazosin and doxazosin studies an additional 4–10% of patients dropped out because they did not tolerate the therapy. Tamsulosin has less effect on blood pressure than alfuzosin (especially in elderly patients) and causes less symptomatic orthostatic hypotension during orthostatic stress testing than terazosin. Conclusions: All α₁-adrenoceptor antagonists seem to have similar efficacy in improving symptoms and flow. The difference between α₁-adrenoceptor antagonists is related to their side effect profile. Alfuzosin and tamsulosin appear to be better tolerated than doxazosin, terazosin and prazosin.