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Primary Prevention of CHD with Lipid-Lowering Drugs



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Am Fam Physician. 2001 May 15;63(10):2050-2052.

The ability of lipid-lowering drugs to reduce coronary heart disease (CHD) events in patients with lipid disorders and known heart disease is well established. This effectiveness of secondary prevention has not been replicated in studies of primary prevention. Early studies of patients at low to moderate risk of death from CHD showed inconsistent results and raised concerns about possible side effects associated with long-term prophylactic treatment. Pignone and colleagues reviewed the evidence for primary prevention of CHD with lipid-lowering drugs. CHD events and associated mortality, and all-cause mortality were used as outcome measures.

They searched electronic databases, the clinical trials registry of the Cochrane Library and the bibliographies of relevant systematic reviews and clinical practice guidelines to identify randomized trials of at least one year in duration that included CHD events and mortality, and all-cause mortality as end points. Although the searches identified more than 500 articles, only four met all of the inclusion criteria.

These four studies involved more than 10,000 patients in the intervention groups and more than 10,000 patients in the control groups. The medications used in the studies were cholestyramine, gemfibrozil, pravastatin and lovastatin. Three of the studies were restricted to men and, in the remaining study, 15 percent of participants were women. The average age of the participants ranged from 47 to 58 years.

Two of the studies reported mean reductions of 10 and 20 percent in total cholesterol at five years. One study reported an 8.5 percent reduction after seven years, and the remaining study claimed an 18 percent reduction at one year. Compared with placebo, treatment reduced the relative risk of CHD events by 30 percent. CHD-related mortality was reduced by 29 percent, but no effect was observed on all-cause mortality. When the meta-analysis was restricted to the three statin drugs, the effects on CHD events and mortality were enhanced, but no significant benefit for all-cause mortality was evident.

The authors conclude that treatment with lipid-lowering drugs, especially statins, reduced the incidence of CHD events and related mortality by about 30 percent. They attribute the lack of effect on all-cause mortality to the relatively low risk of death in the study population. No evidence of an increased incidence of non-CHD deaths was found in the treated patients. The authors call for further research to validate their findings and investigate the effect of longer treatment periods and the primary CHD prevention scope of statin drugs in other population groups.

Pignone M, et al. Use of lipid lowering drugs for primary prevention of coronary heart disease: meta-analysis of randomised trials. BMJ. October 21, 2000;321:1–5, and Hulley SB, et al. Statins: underused by those who would benefit. BMJ October 21,2000;321:971–2.

editor's note: This article was accompanied by an editorial written by Stephen B. Hulley advocating the widespread use of statins for primary prevention—even raising the possibility of availability of these agents without prescription—based on the impressive decrease in the incidence of CHD events and deaths. The editorial indicated that these drugs are not only powerful but safe and more acceptable to patients than diet and other lifestyle interventions. While I agree that statins are useful for lowering CHD risk in patients with dyslipidemias, I wonder if we will one day be asked “you want a statin with that?” at the fast-food counter. Eating well and exercising regularly have enormous benefits for patients, not only in the prevention of heart disease, and to suggest “statins for all” makes my job as a health advocate more difficult. My consolation is that this same journal recently published the updated Sheffield tables, which greatly simplify calculating risks for individual patients. The tables also make discussion of risks easier, because patients can see for themselves the factors that contribute to their risk scores. With a better grasp of risks we can target statin use and other specific interventions for individual patients.—a.d.w.

 


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