Spironolactone Study Reveals 30% Reduction in Heart Failure Mortality
Spironolactone Study Reveals 30% Reduction in Heart Failure Mortality
By William T. Elliott, MD, FACP
Spironolactone has been shown to be highly effective in reducing morbidity and mortality in patients with severe heart failure. In a study to be published in a recent issue of the New England Journal of Medicine, more than 1600 heart failure patients were randomized to spironolactone or placebo. All patients were being treated with an ACE inhibitor and a loop diuretic. Some were also on digoxin. The study was ended early, after a mean follow-up of 24 months, when it was shown that the active treatment group had a 30% reduction in relative death risk (386 deaths in the placebo group, 284 deaths in the spironolactone group). Death from both progressive heart failure and sudden cardiac death was decreased. Patients in the spironolactone group also had improvement in symptoms and a 35% reduction in hospitalizations. The New England Journal of Medicine took the unusual step of releasing the article and accompanying editorial early because of the importance of the findings.
A new proton pump inhibitor (PPI) has been approved by the FDA for marketing in this country. Rabeprazole (Aciphex) will be marketed by Eisai Inc. and Janssen Pharmaceutica for the treatment of gastroesophageal reflux (GERD), duodenal ulcers, and hypersecretory syndromes such as the Zollinger-Ellison syndrome. The drug is dosed as a single 20 mg enteric-coated tablet each day. Rabeprazole, which has been available in Japan and Europe for two years, joins omeprazole (Prilosec) and lansoprazole (Prevacid) in this highly competive market. In a related story, a study from San Diego compared lansoprazole and omeprazole for the treatment of GERD (Am J Managed Care 1999;5:881-886). The drugs were comparable in efficacy at both low- and high-dose regimens. Because lansoprazole is less costly, it was deemed more cost-effective for this indication.
Alprostadil, also known as prostaglandin E1, has been used successfully for years as a treatment for erectile dysfunction (ED). Unfortunately, the drug requires an intracavernous injection or urethal suppository—unacceptable delivery systems for many men. Now researchers from Chicago have tested a topical alprostadil preparation with promising results (J Urol 1999;162:726-732). The application of topical alprostadil plus SEPA, a proprietary transdermal permeation enhancer, to the penis in 47 patients with ED was 67-75% successful in causing erections at one hour. The study participants had ED from a variety of causes including vascular, neurogenic, psychogenic or mixed causes. Although the preparation was generally well tolerated, the vast majority of men noted some penile skin discomfort after using the drug. The study did not test the ability to have intercourse, and future studies will need to address this and partner safety.
Wyeth-Ayerst Laboratories received a mid-August approval from the FDA for zaleplon (Sonata), for the treatment of insomnia. The drug is not a benzodiezepine, rather, it is a pyrazolopyrimidine, a unique new class of medication that binds selectively to GABA receptors in the brain. Zaleplon has a rapid onset and short duration of action, allowing it to be taken on an as-needed basis after a trial of natural sleep has failed. The drug is quickly eliminated; thus, it can be taken late into the night when other sleeping medications might cause residual drowsiness. When taken at least four hours before arising in the morning, it is associated with minimal daytime drowsiness.
From the future files—researchers in Belgium have reported impressive results transferring genetic material into mice with hemophilia A (Proc Natl Acad Sci 1999; 96:10379-10384). The mice were injected with a retrovirus containing the gene to produce factor VIII. Almost half of the treated mice showed stable levels of factor VIII, enough to sustain clotting effectiveness, for months. Gene transfer occurred into liver, spleen, and lungs with predominant factor VIII mRNA expression in the liver. The authors conclude "these findings indicate that a genetic disease can be corrected by in vivo gene therapy using retroviral vectors."
Emisphere Technologies is working on an oral heparin preparation. The results of a phase II trial of oral heparin for prevention of thromboembolic events after hip surgery were presented to the XVIIth Congress of the International Society of Thrombosis in August. The study compared oral heparin preparation to subcutaneous heparin in 123 patients who had undergone elective hip surgery. There was no difference in the activity or safety between the oral or SQ heparin. Phase III studies are being planned. Emisphere is a drug delivery firm that specializes in creating oral forms of parenteral medications.
Searle’s celecoxib (Celebrex) has proven to be the most successful new drug launch ever, with more than 7 million prescriptions in its first six months on the market. But it’s dominance in the new COX-2 inhibitor market has been challenged by Merck’s rofecoxib (Vioxx) which, unlike celecoxib, is indicated for pain as well as arthritis. But celecoxib may soon have a new indication as the FDA recently granted the drug a priority review for the indication of adenomatous polyps. The company has conducted studies with the National Cancer Institute in patients with familial polyposis using colonoscopic surveillance. The priority review means that a decision should be forthcoming for this indication within six months.
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