PARIS — The α-1 blocker alfuzosin prevented overall clinical progression of benign prostatic hyperplasia but had no impact on acute urinary retention in a 2-year, double-blind, placebo-controlled, multinational study that enrolled 1,522 men at high risk of serious outcomes.
Alfuzosin (Uroxatral) reduced the relative risk for any worsening of lower urinary tract symptoms by 26%, according to data reported by Dr. Claus Roehrborn at the annual congress of the European Association of Urology.
A total of 289 patients in both arms of the study had at least one event signalling progression. Symptom deterioration was the most common, occurring in 215 men, followed by surgery related to benign prostatic hyperplasia (BPH) in 87 men and acute urinary retention in 30 men. The overall incidence of events was 16.3% of 754 men on alfuzosin vs. 22.1% of 761 men on placebo.
Dr. Roehrborn of the University of Texas Southwestern Medical Center at Dallas presented the results on behalf of the Alfuzosin Long-Term Efficacy and Safety Study (ALTESS) study group.
He reported that alfuzosin was associated with a 30% reduction in the relative risk of the International Prostate Symptom Score (IPSS) worsening by at least four points. The cumulative incidence of this measure was 11.7% in the alfuzosin arm vs. 16.8% of placebo patients. Patients on alfuzosin also were 22% less likely to have BPH-related surgery: 5.1% required operative interventions vs. 6.5% of the placebo group.
Only the cumulative incidence of acute urinary retention was similar in the two groups: 2.1% of the alfuzosin group vs. 1.8% of placebo. “This may be attributable to selection of patients with higher risk of retention,” Dr. Roehrborn said.
He noted that the study was designed to enroll high-risk patients aged 55 or older. The criteria included an IPSS at or above 13, a Qmax of 5–12 mL/sec for a voided volume of 150 mL or more, postvoid residual urine of 350 mL or more, prostate size of 30 g or more as estimated by a digital rectal exam, and a prostate-specific antigen concentration of 1.4–10 ng/mL.
Patients were enrolled from May 2001 to March 2005 at 148 urology centers in North America, Europe, Australia, the Middle East, and South Africa, according to Dr. Roehrborn's poster. Subjects randomized to alfuzosin took 10 mg daily for 2 years.
About one-third of the patients—513 men-—dropped out of the study. Lack of efficacy or disease progression prompted 9.9% of the alfuzosin patients and 14.5% of the placebo group to withdraw from the trial. Adverse events led to 9.4% and 8.1% of withdrawals, respectively.
Alfuzosin had a similar side effect profile to placebo and was well tolerated, according to Dr. Roehrborn. The most common adverse event was dizziness in both arms of the study (alfuzosin, 6.0% and placebo, 4.6%). Only 1.2% of patients in the alfuzosin arm had hypotension or postural hypotension. Ejaculatory disorders were rare as well (0.4%).
Dr. Roehrborn also reported significant improvements in IPSS scores over 2 years and peak flow rate at 12 months for alfuzosin vs. placebo. Over 2 years, prostate-specific antigen levels decreased 0.6% with alfuzosin, but increased 3.6% with placebo.
The results are similar to those for doxazosin in the Medical Therapy of Prostatic Symptoms study, Dr. Roehrborn said. “We have learned the limits and the utilities of α-blockers in the long term for patients with lower urinary tract symptoms and benign prostatic hyperplasia.”
Postvoid Residual Found Predictive
ALTESS trial investigators were surprised to find that postvoid residual urine could predict progression of benign prostatic hyperplasia symptoms over time, according to Dr. Roehrborn.
He reported that increasing postvoid residual (PVR) scores were associated with a worsening of symptoms in the alfuzosin and the placebo arms of the study.
The predictive power of PVR has been underestimated when patients are observed longitudinally. Guidelines for long-term monitoring of benign prostatic hyperplasia should be recognized, he said.
“We have brushed it [PVR] off as an unreliable and not reproducible value,” when in fact the opposite is true.
Dr. Roehrborn reported that age was not a risk factor for any of the study's outcomes, but higher baseline prostate-specific antigen concentration was predictive of surgery and of acute urinary retention. This was true whether patients were taking alfuzosin or placebo.
Analysis of ALTESS data suggests that the severity of baseline symptoms as measured by the International Prostate Symptom Score is unlikely to predict thresholds of symptoms worsening, Dr. Roehrborn added. He reported that patients with lower scores were more likely to have their symptoms worsen, whereas patients with higher IPSSs were more likely to have surgery.