Selective and non-selective α-blockers for BPH: Application
Application to clinical practice
An important issue is extrapolation of the results of alfuzosin (Uroxatral) to the terazosin (Hytrin) we prescribe in Canada. Although the affinity αa/αb receptor ratio is similar for alfuzosin and terazosin, their incidence of association with signs of hypotension differ. In placebo-controlled trials, patients treated with terazosin experienced obvious signs of hypotension, whereas incidence among patients receiving tamsulosin (Flomax) and alfuzosin (Uroxatral) was similar to that among patients treated with placebo. This indirect comparison between α-blockers has, of course, important limitations but should be borne in mind when extrapolating results to terazosin (Hytrin).
Two trials have directly compared tamsulosin (Flomax) with terazosin (Hytrin). One single-blind trial was conducted among Asian men with high-normal blood pressure levels and symptomatic benign prostatic hyperplasia (BPH). They received 0.2 mg of tamsulosin (half the dose white men would receive) or 5 mg of terazosin daily. Both groups experienced significant improvement in Qmax and symptom scores, but the number of side effects and the reduction in standing blood pressure levels from baseline (-16.1/-11.4 mmHg for the terazosin group vs -9.4/-5.4 mmHg for the tamsulosin group) was statistically greater in the terazosin group. The authors did not mention whether lowering blood pressure levels had an effect on symptoms. The other trial included normotensive healthy men, only half of whom had BPH. Patients were randomized in a double-blind fashion to receive 0.4 mg of tamsulosin (Flomax) or 5 mg of terazosin (Hytrin) daily. Significantly more patients treated with terazosin experienced symptomatic hypotension, but there was no difference in the proportion of patients experiencing asymptomatic hypotension. No differences were observed in blood pressure. These two studies have several important limitations, namely the smaller tamsulosin dose used and the fact that some patients did not have benign prostatic hyperplasia. The results, however, when interpreted with results of the placebo-controlled trials, support some of the findings of the alfuzosin-tamsulosin trial. These findings include a lower incidence of signs of hypotension in normotensive and hypertensive patients receiving tamsulosin and, possibly, no significant decrease in blood pressure in patients with high-normal (or stage 1) hypertension in the tamsulosin group.
Several categories of patients with symptomatic BPH can present a treatment dilemma: hypertensive patients already stabilized using other antihypertensive medications, normotensive patients, normotensive patients receiving other antihypertensive agents for other indications (eg, an angiotensin-converting enzyme inhibitor [ACE-I] for diabetic nephropathy), and patients for whom suboptimal doses of α-blockers reduce benign prostatic hyperplasia symptoms but cause hypotensive side effects. For these patients, an attempt to initiate or reinstitute a non-selective α-blocker with more frequent follow-up visits and a very slow titration of dose could be tried, or tamsulosin could be initiated, provided patients can afford it (approximately $36/month). The costs of tamsulosin (Flomax) and terazosin (Hytrin) are similar, but only terazosin is covered on most provincial drug plans.
Two important benefits can be derived from using tamsulosin (Flomax). First, because the dose does not need to be titrated, there is less risk of confusion for patients and fewer follow-up visits. Second, the possibility of a faster onset of action would mean a faster improvement in quality of life for patients.
Several questions, such as whether tamsulosin also has a favourable effect on lipids, whether it decreases risk of falls, and what its long-term effects are, remain unanswered.
Bottom line
• Tamsulosin (Flomax), a uroselective α-blocker, at a dose of 0.4 mg, appears to be as effective as alfuzosin (Uroxatral), a non-selective α-blocker. Unlike terazosin (Hytrin), the dose of tamsulosin does not need to be titrated. Tamsulosin (Flomax) produced slightly fewer symptoms of hypotension, but this did not translate into clinical outcomes, such as more falls. These benefits might not be important because terazosin is now available in starter packs to assist patients to titrate the dose themselves.
• Patients who already have good blood pressure control with other preferable agents (eg, diabetics receiving ACE-Is) and who had severe hypotensive effects with non-selective α-blockers might prefer a uroselective agent.
• Most of our patients with benign prostatic hyperplasia are also at risk for hypertension, and a non-selective α-blocker treats both conditions with one pill. Differences between the two treatments were small, and patient-oriented outcomes were similar.
• Tamsulosin (Flomax) is slightly more expensive and does not seem to confer greater benefits for most of our patients.
Posted in: Drugs: α-blockers