Treatment of Hyperlipidemia

,

Applied Evidence

Treatment of Hyperlipidemia

J Fam Pract. 2002 April;51(4):370-376

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References

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4. Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Executive Summary. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3xsum.pdf Accessed April 16, 2001.

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6. Henkin Y, Shai I, Zuk R, et al. Dietary treatment of hyperlipidemia: Do dietitians do it better? A randomized, controlled trial. Am J Med 2000;109:549-55.

7. Ornish D. Avoiding revascularization with lifestyle changes: the multicenter lifestyle demonstration project. Am J Cardiol 1998;82:72T-76T.

8. Ornish D, Scherwitz LW, Billings JH, et al. Intensive lifestyle changes for reversal of coronary heart disease. JAMA 1998;280:2001-7.

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10. Mensink RP, Plat J. Efficacy of dietary plant stanols. In: New developments in the dietary management of high cholesterol. New York: McGraw-Hill; 1998;27-31.

11. Blair SN, Capuzzi DM, Gottlieb SO, et al. Incremental reduction of serum total cholesterol and LDL with the addition of plant stanol ester-containing spread to statin therapy. Am J Cardiol 2000;86:46-52.

12. Miettinen TA, Puska P, Gylling H, et al. Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesteremic population. N Engl J Med 1995;333:1308-12.

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16. EBM Reviews. Database of abstracts of reviews of effectiveness [database online]. Psyllium-enriched cereals lower blood total cholesterol and LDL cholesterol, but not HDL cholesterol, in hypercholesterolemic adults: results of a meta-analysis. July 2001; v1, accession no. 00125498-100000000-00737. Available at: http://www.ovid.com/products/databases. Accessed Oct. 29, 2001.

17. EBM Reviews. ACP Journal Club [database online]. Soy protein intake decreases total and LDL cholesterol and triglyceride levels. March/April 1996; 124:41, accession no. 00021607-199603000-00013. Available at: http://www.ovid.com/products/databases. Accessed April 4, 2001.

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Although diet therapy has shown a modest redution in total cholesterol in clinical trials, no clear evidence shows that a diet low in saturated fat and cholesterol will reduce cardiovascular morbidity and mortality.^5,6 Many people find it difficult to change their dietary habits and to maintain healthier ones. Systematic reviews of observational studies have found that increased consumption of fruits and vegetables is associated with lower incidence of heart attack and stroke. However, the potential for bias and confounding factors in such studies makes them less convincing than randomized controlled trials (RCTs).⁵

The Ornish program, in which CAD or CAD-equivalent patients pursue intense lifestyle modification for up to 3 years, has shown that revascularization procedures can be avoided. Treatment groups that ate a very-low-fat diet, received intervention on stress management, and followed a prescribed exercise program showed similar improvement in angina symptoms versus the revascularization group. Another trial showed regression of atherosclerotic plaque on angiograms.^10-12

Other nonpharmacologic options include plant stanols (2 grams/day) and soluble fiber (10 to 25 grams/day) to reduce LDL-cholesterol. Plant stanols have a structure similar to that of cholesterol and interfere with cholesterol absorption when eaten along with a typical diet, resulting in reduction of blood cholesterol levels. Plant stanols and sterols can be found in certain margarines and salad oils and can be taken with each meal as substitutes for other sources of dietary fat.^7-9 No RCTs have shown that these substances reduce cardiovascular events or overall mortality.

Herbal products and dietary supplements

A survey found that as many as 50% of respondents with elevated cholesterol levels would prefer an over-the-counter product such as garlic, yeast, or soy products.¹³ Studies of products promoted for lipid-lowering effects were found to have a modest effect on lipid levels^13-18 (Table 2); however, no RCTs were found that assessed patient-oriented outcomes. Because herbal products and supplements have modest effects on lipid levels and because long-term safety data are lacking, such products should be used with caution for treatment of hyperlipidemia.

TABLE 2
PHARMACOLOGIC AND NONPHARMACOLOGIC INTERVENTIONS

Strength of Recommendation*	Treatment	Type of Benefit	Cost Per Month ($)	Comments
A	Statins	OM, CVM	40–110	Well tolerated
B	Fibric acids	CVE	60–70	All male subjects in both primary and secondary trials
B	Niacin	CVE	10–80	Watch for adverse reactions (flushing, elevated glucose, liver function tests)
B	Bile acid resin	CVE	40–60	Ideal agent for patients with severe liver disease; watch for drug interactions
B	Lifestyle modification	Lipid	Varies	No strong evidence from randomized clinical trials on primary prevention of major coronary events or mortality
B	Soy products	Lipid	20	FDA has approved labeling soy products for cholesterol reduction
B	Red yeast	Lipid	20–30	Active ingredient is lovastatin; should be treated as lovastatin
B	Plant stanols	Lipid	20–30	Substitute for other source of fat calories; must be taken with each meal
C	Fish oils	Lipid	5–10	Use with caution because of high caloric value and cholesterol content in products; may increase cholesterol level with long-term use
C	Garlic	Lipid	10–20	Conflicting results with clinical trials
C	Green tea	Lipid	15	Epidemiologic study data
* Criteria correspond to US Preventive Services Task Force categories (A = strong evidence to support recommendation, B = fair evidence to support recommendation, C = insufficient evidence to recommend for or against). CVE denotes reduction in cardiovascular events; CVM, reduction in cardiovascular mortality; lipid, reduction in lipid levels only; OM, reduction in overall mortality.

Pharmacologic treatment

Clinical trials of hyperlipidemia therapy should address outcomes that matter most to patients, such as morbidity, mortality, quality of life, and cost, rather than stressing disease-oriented evidence, such as the ability to reduce cholesterol levels. For this review we identified major long-term RCTs that included significant coronary events or mortality as the primary outcomes. Table 3 summarizes the results of primary and secondary prevention studies.

TABLE 3
PHARMACOLOGIC INTERVENTION

Reduction in Risk
Intervention	Major Coronary Events		All-Cause Mortality	Comments
	ARR (%)	NNT	NNT
Primary Prevention
Statins	2.0–2.3	44–49	NS	Studies on normal and hypercholesterolemic patients. Mean age was 47–58 years; all patients were men except for 1 statin study that included a small number of women
Gemfibrozil	1.4	71	NS
Cholestyramine	1.7	59	NS
Secondary Prevention
Statins	3–3.6	28–33	24–28	Mean age was 55–64 years. Participants were male except for the 3 statin studies and the benzafibrate study that enrolled a small number of women. Cholesterol eligibility criteria varied among the studies and included patients with normal or elevated total and LDL levels or low HDL levels
Gemfibrozil	4.4	23	NS
Benzafibrate	1.4	71	NS
Niacin	6.2	17	NS
ARR denotes absolute risk reduction in percent; NNT, number of needed to treat for 5 years to prevent 1 adverse outcome; NS, not significant.

Primary prevention

Primary prevention studies have investigated the treatment of middle-aged men with hyperlipidemia and of men and women with average cholesterol levels.^19-23 Results showed similar positive outcomes on reducing coronary events in all groups (Table 3). A systematic review and a meta-analysis of primary prevention studies also demonstrated that drug therapy reduced cholesterol levels and resulted in statistically significant lowering of cardiovascular events in the treated group compared with placebo without any significant reduction in overall mortality.^5,24 Absolute risk reductions ranged from 1.4% to 2.3%. In other words, the number of patients that would have to be treated for 5 years to prevent a single major coronary event was 44 to 49 for the statins, 71 for gemfibrozil, and 59 for cholestyramine.