1044 © 2 0 0 3 B J U I N T E R N A T I O N A L | 9 2 , 1 0 4 4 – 1 0 4 8 | doi:10.1046/j.1464-410X.2003.04537.x LETTERS 1 Roehrborn CG, Van Kerrebroeck P, Nordling J. Safety and efficacy of alfuzosin 10mg once-daily in the treatment of lower urinary tract symptoms and clinical benign prostatic hyperplasia: a pooled analysis of three double-blind, placebo-controlled studies. BJU Int 2003; 92: 257–61 2 Kirby RS. Doxazosin in benign prostatic hyperplasia. effects on blood pressure and urinary flow in normotensive and hypertensive men. Urology 1995; 46: 182–6 3 Kirby RS. Terazosin in benign prostatic hyperplasia. effects on blood pressure in normotensive and hypertensive men. Br J Urol 1998; 82: 373–9 4 The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. NIH Publication 03–5233: NIH, May 2003 5 di Priolo L, Priore P, Gocco C et al. Dose-titration study of alfuzosin, a new alpha1-adrenoceptor blocker, in essential hypertension. Eur J Clin Pharmacol 1988; 35: 25–30 6 Sega R, Marazzi ME, Bombelli M et al. Comparison of the new alpha1-blocker, alfuzosin with propranolol as first-line therapy in hypertension. Pharmacol Res 1991; 24: 41–52 Reply Dr Wyllie made the following two points: (i) the blood pressure was relatively low in the hypertensive group; and (ii) the absence of a decrease in blood pressure under alfuzosin in the hypertensive group may be explained by the relatively low baseline blood pressure in this group, because alfuzosin has previously been shown to have a significant effect on blood pressure in other studies of hypertensive patients. The responses, provided in the same order as the comments, are: (i) Patients included in the analysis of hypertensive patients in Table 3 of the paper were those reporting a history of hypertension at baseline and also include those with controlled hypertension (i.e. normal blood pressure) on antihypertensive medications. This would explain the mean values in the Table, which are lower than expected for the definition of hypertension. (ii) Dr Wyllie also mentions that alfuzosin had been shown to lower blood pressure in two early studies of hypertension [1,2]; in these studies, older formulations (not once daily) were used, at relatively higher doses (5 mg twice daily to 20 mg four times daily [1]; 2.5 mg up to 10 mg twice daily [2]); moreover, the results showed a significant difference in favour of propranolol at 4 weeks and there was no equivalence of alfuzosin vs propranolol [2], as mentioned. The clinical uroselectivity of an a-blocker (clearly shown with alfuzosin) is related to many factors that contribute at different levels to the final benefit/risk ratio, e.g. pharmacological selectivity, absence of passage through the blood–brain barrier, preferential distribution in prostatic tissue, dose, and formulation (C max , T max ). Affinity studies on human-cloned a1-receptor subtypes showed that alfuzosin, like terazosin and doxazosin, is devoid of significant receptor subtype selectivity [3,4], but in isolated human tissues, alfuzosin had the highest selectivity ratio for the prostate over vascular tissue (ratio 144) compared with tamsulosin (90), doxazosin (51) and terazosin (19) [5]. In addition, in a conscious-rat model, it was shown that the primary effect of alfuzosin is as a urethral relaxant and not an antihypertensive effect [6]. Alfuzosin also penetrates the brain poorly, which may contribute to a lower incidence of CNS- related adverse events, e.g. dizziness and somnolence [7]. A preferential distribution in prostatic tissue has also been reported [8]. While it is possible that high doses of other SAFETY AND EFFICACY OF ALFUZOSIN 10 MG ONCE-DAILY IN THE TREATMENT OF LOWER URINARY TRACT SYMPTOMS AND CLINICAL BENIGN PROSTATIC HYPERPLASIA: A POOLED ANALYSIS OF THREE DOUBLE-BLIND, PLACEBO- CONTROLLED STUDIES Sir, I read with interest the clinical summary of the once-daily formulation of alfuzosin [1] which confirms the utility of a-adrenoceptor antagonists for treating LUTS associated with BPH. As would be expected from any study involving Prof Roehrborn, I particularly appreciate the attention to detail. In this context I wonder whether, in the same way that BPH symptoms are stratified as mild, moderate or severe, if patients with BPH who were ‘hypertensive’ should be stratified similarly. In the present study the hypertensive patients were entered with a mean blood pressure of ª 147/88 mmHg, whereas in the comparable studies involving doxazosin [2] and terazosin [3] the mean point for the ‘hypertensive’ groups was anywhere up to 162/99 mmHg. Although the patients in the alfuzosin report met the definition of the 7th Joint National Committee (JNC-7) on Hypertension as being hypertensive (i.e. a systolic pressure of 140–159 or a diastolic of 90–99 mmHg) [4], many of the group judged by the same criteria would be considered to be normotensive. Intriguingly, in two early studies alfuzosin lowered blood pressure in essential hypertension, producing equivalent reductions to propranolol [5,6]. On this basis, although not affecting the interpretation of the data, the reader might want to consider Prof Roehrborn’s hypertensive patients as having what was known as ‘borderline’ hypertension. However, after JNC-7 most of the group would probably be best described as having ‘pre-hypertension’ or Stage 1 hypertension [4]. M.G. WYLLIE, PhD, Urodoc Ltd, Herne Bay, Kent, UK WRITE TO THE EDITOR AT BJU INTERNATIONAL, 47 ECCLES STREET, DUBLIN 7, IRELAND