THERAPEUTICS REPORT

The recently published results of the Heart and Estrogen/progesteroneReplacement Study (HERS) (JAMA, Aug19, 1998; 280:605-613) presents information abouthormone replacement therapy (HRT) in a population of older women with severe coronaryheart disease (CHD). The major clinical trial followed a randomized protocol whichincluded 2,763 women at 18 medical centers in the United States and evaluated HRT as atreatment for preventing CHD progression, specifically nonfatal myocardial infarction (MI)and death from CHD. The article reported that daily use of HRT did not reduce the overallrisk for MI and CHD death in postmenopausal women with established CHD. However, HRT didproduce a significant beneficial effect over time. The study was not designed to evaluateprimary prevention in a population of healthy women, which represents the most typical useof HRT. Rather, it looked a subset of women with an average age of 67 years who haveestablished CHD.

In the first year of the study, women treated with HRT experienced anincrease in second CHD events compared with placebo (RR 1.52, 95% CI 1.01-2.29). Withcontinuing treatment, this initial increase was reversed, and HRT resulted in less secondevents by the 4^th and 5^th years of treatment (RR 0.67, 95% CI0.43-1.04). ABasedon these findings, we don=t recommend starting estrogen plus progestin for the purpose ofpreventing heart attacks in postmenopausal women with existing heart disease,@ stated Stephen B.Hulley, MD, Professor and Chair of Epidemiology and Biostatistics at University ofCalifornia, San Francisco (UCSF) and the leader of the study. AThere was no overallbenefit during the 4 years of the trial, and the risk of heart attacks seemed to increasesoon after starting hormones. But women who are already taking estrogen plus progestincould decide to continue, given the apparent decrease in risk of heart attack afterseveral years.@

Selective COX-2 inhibitors are in phase III of clinical trial withcelecoxib (Celebra⁷/Searle) and MK-966 (Vioxx⁷/Merck)expected to have a filed NDA in the near future. It is expected that other companies willdevelop agents of this class. Although specific data are not available, it appears fromEuropean studies that the degree of damage to the gastric mucosa with these selectiveCOX-2 agents may be significantly lower than with older non-selective agents.

One of the dominant nutritional recommendations is for a diet high incomplex carbohydrates. This belief accounts for the foundation of the FDA=s food guide pyramidwhich suggests 6-11 servings of grains per day. The pyramid emphasizes high intakes ofbreads, cereals and potatoes. The base level of the pyramid encompasses a variety of foodsfrom a large range of refinement techniques. Recent studies suggest that grain refinementin the food industry is contributing to some of our nations health problems.

A paper by Jacobs et al (1) challenges the current generalizations made bythe food guide pyramid. They examine intakes of whole and refined grains in relation tothe risk of ischemic heart disease (IHD). In their analysis, which is part of the ongoingIowa women=shealth study, consumption of whole grains was associated with a decreased risk of IHDwhereas intake of refined grains was associated with an increased risk. Although the foodpyramid does not entirely account for differences between whole and refined grains, thesefindings are consistent with the current evidence that fiber consumption is inverselyrelated to risk for heart disease.

(1) Jacobs DR, Meyer KA, Kushi LH, Folsom AR. Whole grain intake mayreduce the risk of ischemic heart disease death in post-menopausal women: the Iowa Women=sHealth Study. Am J Clin Nutr 1998; 68:248-57.

The United States Pharmacopeia (USP) is now taking steps to solve the lackof information and regulation. The organization has began publishing fact sheets whichsummarize the available reputable scientific data on certain herbs. For consumers, factsheets on Comfrey, Feverfew, Ginger, Hypericum (St. John=s Wort) and Valerianroot are currently available at the USP website, located at http://www.usp.org/did/mgraphs/botanica/. They are currently developing similar fact sheets for ginkgobiloba, saw palmetto and garlic among others. The fact sheets describe each herb=s use, precautions toconsider and side effects to watch out for.

The FDA has granted marketing approval for hepatitis B (recombinant)vaccine (Engerix B⁷/ SmithKline Beecham) for use in patients with chronic hepatitis Cinfection. Raymond Koff, MD of Philadelphia=s MetroWest Medical Center stated: AIt is important thatpeople with hepatitis C get vaccinated against hepatitis B...If infected with hepatitis B,hepatitis C patients are at increased risk for acute liver failure.@ The vaccine will beadministered initially, followed with addition injections at one and six months. Mostfrequent side effects are redness and swelling at the injection site.

Marketing approval has been granted for estradiol/norethindronetransdermal system (CombiPatch⁷/Rhone-Poulenc Rorer and Noven) for relief of moderate-to-severevasomotor symptoms in menopausal women with an intact uterus.

Approval has been granted for a combined diphtheria, tetanus, andacellular pertusis vaccine (Certiva⁷/North American Vaccine) for use in children aged 6 weeks to 7years. Side effects, as reported in a Swedish study of 3,450 infants, includedirritability and redness/pain at the injection site. It will be marketed by the RossProducts Division of Abbott Laboratories.