Recent Cholesterol Report Focuses on Prevention of Coronary Artery Disease

By William T. Elliott, MD, FACP

The executive summary of the third report of the National Cholesterol Education Program (NCEP) was published in May. The report, called Adult Treatment Panel III (ATP III), updates national guidelines for the detection and treatment of hypercholesterolemia, last published in 1993. Perhaps the biggest change in cholesterol management in the last 8 years has been the focus on primary prevention of coronary artery disease (CAD). ATPIII provides a tool for physicians to grade their patients’ risk of CAD within 10 years. The report suggests aggressive treatment for those with risk factors, including using drug therapy to lower LDL cholesterol to 100 mg/dl. Another significant change is the elevation of diabetes to the equivalent of CAD when considering lipid-lowering therapy. The guidelines also suggest that anyone with an LDL cholesterol greater than 130, HDL less than 40, or a triglyceride level greater than 200 should be considered for drug therapy. The expert panel also recommends that a fasting lipid panel should be the standard screening exam. The executive summary is available in the May 16 issue of JAMA (JAMA. 2001;285:2486-2497). More information is also available at http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm.

Migraine Treatment

The FDA has approved a new triptan for the treatment of migraine. Pharmacia’s almotriptan is approved for migraine in adults with or without aura. The drug, which will be sold under the trade name "Axert," is touted as being as effective as sumitriptan but with significantly less side effects, especially chest pain (company data).

Oral Contraceptives

A new low-dose oral contraceptive was also approved in the last month. Berlex’s Yasmin contains 30 mcg of ethinyl estradiol and 3 mg of the progestin drospirenone. It is the latter agent that makes this combination unique. Drospirenone, an analogue of spironolactone, has diuretic effects and, thus, is ideal for women with premenstral bloating and water retention.

Metered Dose Inhalers

In a study that could only have come from Scotland (this editor’s ancestral homeland), discarded toilet paper tubes have been found to be effective spacers for use with metered dose inhalers. The cardboard tubes were compared to no spacer and the commercially available Aerochamber spacer device. Both the cardboard spacer and Aerochamber performed better than using the MDI without a spacer, with the Aerochamber performing better, but not significantly so. Fowler and associates conclude: "If a spacer is required for reasons other than increasing delivered drug dose, then the addition of a readily available cardboard tube will fulfill many of the required functions with no expense to the patient." (Chest. 2001;119:1018-1020).

Antifungal Warnings

The popular antifungal itraconazole (Sporanox—J&J) is warning doctors not to use the drug in patients with congestive heart failure (CHF) or a history of CHF. The warning is the result of a number of deaths from CHF among patients taking the drug. The company has not specified the number of deaths. J&J is also warning doctors not to use itraconazole in combination with the antiarrythmic dofetilide (Tikosyn) or erythromycin, and urges caution when using the drug with calcium channel blockers.

Cholesterol Lowering Therapy

Older patients may benefit more from cholesterol lowering therapy than younger patients according to an Australian study. More than 9000 patients with a history of CAD were studied, of which 3500 were age 65 to 75. Patients were randomized to pravastatin 40 mg/d or placebo, and were followed for an average of 6 years. In patients 65 to 75 years of age, pravastatin therapy reduced mortality by 21% (CI, 7-32%), death from coronary heart disease by 24% (CI, 7-38%), coronary heart disease death or nonfatal myocardial infarction by 22% (CI, 9-34%), myocardial infarction by 26% (CI, 9-40%), and stroke by 12% (CI, 15-32%). For every 1000 older patients treated over 6 years, pravastatin prevented 45 deaths, including deaths from myocardial infarction and strokes. The rate of decrease was similar for younger and older patients, but since older patients were at a higher absolute risk of death and major coronary events, the benefit was greater for those age 65 to 75 (Ann Int Med. 2001;134:931-940).

Allergy Medicine Wants OTC Status

An unprecedented battle is shaping up in Washington over the status of 3 popular prescription allergy medications. Wellpoint Health, one of the nation’s largest HMOs has petitioned the FDA to switch loratidine (Claritin—Schering-Plough), fexofenadine (Allegra—Aventis), and cetirizine (Zyrtec—Pfizer) to over the counter (OTC) status, thus making them available to consumers without a prescription and removing them from HMO drug benefit plans. The 3 drugs currently account for revenues of $4.7 billion. The issue before the FDA is the relative safety of these "nonsedating" antihistamines compared to currently available OTC antihistamines such as diphenhydramine and hydroxyzine. In a bizarre twist, the manufacturers are arguing to keep the drugs available only by prescription, and thus paid for by third-party payors, arguing that the drugs are too new to be considered for OTC status and that allergic rhinitis requires a doctor’s diagnoses. Although a panel of the FDA has approved a prescription-to-OTC switch for the 3 drugs, it is unclear whether the FDA has the ability to force the switch against the companies’ wishes.

Beta Blockers and CHF

Do beta blockers benefit patients with advanced congestive heart failure? Subsequent articles in the May 31 New England Journal of Medicine give conflicting results. In the first study, more than 2000 patients with severe heart failure were randomized to carvedilol therapy or placebo for an average of 19.4 months. Over the study period there were 190 deaths in the placebo group and 130 deaths in the carvedilol group, and a 24% decrease in the combined risk of death or hospitalization with carvedilol (N Engl J Med. 2001;344:1651-1658). In the second study, 2700 patients with severe heart failure were randomized to treatment with the beta blocker bucindolol or placebo. The study was stopped early because no significant overall survival benefit was shown with bucindolol (N Engl J Med. 2001;344:1659-1667).