Terazosin

ATLANTA -- The rational way to utilize [alpha]-blocking agents in benign prostatic hyperplasia is to prescribe terazosin (Hytrin) as first-line therapy, Dr. Muta M. Issa advised at a meeting on clinical nephrology sponsored by the National Kidney Foundation.

Reserve the far costlier alternatives, doxazosin (Cardura) and tamsulosin (Flomax), for men who experience unacceptable side effects on terazosin.

The small differences in side effects between the agents aren't commensurate with the huge cost differences, said Dr. Issa, a urologist at Emory University and the Atlanta Veterans Affairs Medical Center.

He and his colleagues at the Atlanta VA have calculated the cost per 1,000 treated patients per year at that institution as $56,000 for terazosin, $192,000 for doxazosin, and $308,000 for tamsulosin.

At an institution such as the Atlanta VA, which serves half a million patients, mostly aging men, the annual savings obtained through a terazosin-first policy reach into the multimillions.

Many physicians are unsure of the appropriate therapeutic role for the [alpha]-blockers since the National Institutes of Health earlier this year halted the doxazosin arm of the massive, 42,000-patient Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) due to a doubling of the risk of congestive heart failure and a 19% increase in stroke risk in doxazosin-treated patients compared with those randomized to chlorthalidone for their high blood pressure.

At the time, ALLHAT Chairman Dr. Curt D. Furberg, professor and chairman of public health sciences at Wake Forest University, Winston-Salem, N.C., declared the a-blockers are "not recommended" as first-line anti-hypertensive therapy and "inferior as second- and third-line agents for hypertension.

But Dr. Issa said he still considers [alpha]-blockers to be the clear first-line therapy for benign prostatic hyperplasia, a view that he said is shared by the great majority of urologists.

Since ALLHAT, however, he routinely obtains a cardiology consult when he wants to prescribe an [alpha]-blocker to a patient whom he knows or suspects may have significant heart disease.

He predicted that [alpha]-blockers will continue to see widespread use in benign prostatic hyperplasia, because affected men are eager for symptomatic relief and there's really no practical alternative in the early stages.

Finasteride (Proscar) is effective only after the prostate has grown larger than 40 g. And few men are interested in going under the knife, laser, or radiofrequency ablator for mild BPH.

Roughly 70%-75% of patients who receive an [alpha]-blocker have significant improvements on the International Prostate Symptom Scores. All three [alpha]-blockers are long-acting, once-daily agents. Side effect profiles of the three drugs are quite similar.

Although tamsulosin is marketed as being more prostate-selective, Dr. Issa said that he and others have found, at most, only faint clinical differences.

Expect about a 30% dropout rate m patients receiving the [alpha]-blocker therapy cautioned Dr. Issa. Dropout is often credited to disease progression.

The [alpha]-blockers don't shrink the prostate; they reduce glandular tension applied by the prostate's substantial fibromuscular component. This allows urine to pass more freely.

Finasteride, in contrast, shrinks prostatic glandular tissue. But until the prostate exceeds 40 g, there is little glandular tissue for the drug to shrink.

Smaller prostates are comprised predominantly of the fibromuscular element, which finasteride doesn't affect.

It takes 3-6 months for finasteride to exert its maximum effect but responders will notice improvement after about 1 month. Large studies demonstrate that finasteride decreases the urinary retention rate on average by 57% and prostate volume by 18% at 4 years.

Finasteride markedly decreases prostate-specific antigen levels. To estimate a treated patient's true PSA, simply multiply the measured value by two, Dr. Issa explained.

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