Common prostate drug is ineffective - Hytrin works better - Hytrin vs Proscar

Healthfacts, Sept, 1996

The first study to compare the two most commonly prescribed drugs for prostate enlargement has been published by the Veterans Affairs Cooperative Group (New England Journal of Medicine, 22 August 1996). It found Proscar to be ineffec- tive and Hytrin to be helpful in alleviating the urinary symptoms that occur in older men whose prostates have enlarged to the point of constricting the urethra. The condition is called benign prostatic hyperplasia (BPH).

Both drugs were compared, separately or in combination with a placebo, in a large multi-center study headed by Herbert Lepor, M.D. of New York University Medical Center, New York City. The study was funded in part by Merck & Company and Abbott Laboratories, manufacturers respectively of Proscar and Hytrin. Direct comparison of two drugs prescribed for the same condition is highly unusual. For FDA approval, a new drug need only be proven more effective than a placebo.

Proscar, the first drug developed specifically to treat BPH, generated excite- ment on Wall Street well in advance of its 1992 FDA approval. (See HealthFacts, July 1991.) But Merck's hopes for billion dollar sales appeared to be dashed once the required testing showed a less than sterling per- formance. Proscar did better than the placebo, but not much better. The clini- cal trial showed that Proscar can shrink the prostate somewhat, but symptom improvement was reported by only 31% of the Proscar-treated men, compared to 17% of those taking a placebo (New England Journal of Medicine, 22 October 1992).

This did not stop Merck from mounting a prostate awareness education campaign complete with direct-to-consumer advertising. (See Disease Awareness=More Rxs, HealthFacts, December 1992). This aggressive marketing campaign, which also targeted physicians, paid off. Proscar soon became a topselling drug. Effec- tiveness, such as it is, lasts only as long as the drug is taken, so Proscar became a drug company's dream: lifelong therapy.

Initially for Hypertension

Hytrin was initially approved in 1987 as a treatment for hypertension and later found to be effective in alleviating symptoms of BPH. It received approval as a BPH treatment in 1993.

For the new comparison study, 1,229 men were given either a placebo, Hytrin, Proscar, or a combination of the two drugs. The participants ranged in age from 45 to 80 years. 87% were white; 11% were black; 1% Asian or Pacific Islanders; and 0.5% were Native Americans. After one year, Hytrin was shown to be more effective than Proscar in improving symptoms and the rate of urinary flow. Proscar shrank the prostate without improving symptoms.

Effectiveness was determined according to a symptom scoring system devised by the American Urological Association. (Obstruction of the urine flow often causes difficulty in urinating and frequent urination, which in turn leads to many nightly trips to the bathroom and sleep disruptions.) The men taking Hytrin alone or in combination reported a six point decrease in symptom scores, whereas the men on Proscar or the placebo reported only three- and two-point decreases, respectively. Men taking Proscar experienced impotence and diminished sex drive at a higher rate than the other participants.

Proscar isn't likely to drop out of the market despite the new study's nega- tive results. Previous studies have shown that the drug can outperform the placebo. Dr. Lepor and colleagues speculate that this is due to the inclusion of more men with larger prostate glands in the earlier research projects. Thus, they suggest, Proscar may be helpful only to men with glands showing the most enlargement.

Merck has already taken off on this possibility. The day the Veterans Affairs study appeared in The New England Journal of Medicine, The New York Times reported that Merck has an unpublished meta-analysis of six major clinical trials of Proscar which confirmed the drug's efficacy. Though Merck and Abbott Laboratories had approved the Veterans Affairs study design and each pharmaceutical company had a physician representative listed among the new study's ten authors, a Merck spokesperson told The New York Times that the Veterans Affairs study was not designed properly.

Hytrin Less Costly

Neither Hytrin nor Proscar is available generically, but Hytrin is less expensive. The Medical Letter reported in 1994 that a 30-day treatment with 2, 5, or 10 mg/day of Hytrin costs $33.97, compared to $54.70 for 5 mg/day of Proscar.

Until Hytrin and Proscar came along, surgery was the only option for men who were distressed enough to seek treatment for BPH symptoms. Each drug has a different way of working. Hytrin relaxes the smooth muscle around the bladder neck and prostate, thus alleviating constriction of the urethra. Proscar can shrink the prostate by blocking the conversion of testosterone to dihydrotestosterone.

People over the age of 60 often have reactions to drugs that are different from those of younger people. The following cautions about Hytrin appear in The Essential Guide to Prescription Drugs by James W. Long, M.D. and James J. Rybacki, Pharm.D. (New York: HarperCollins Publishers, Inc., 1996):