What levels of cholesterol should be treated for primary prevention? - Clinical Inquiries - Brief Article - Statistical Data Included

Journal of Family Practice, May, 2002 by Terry L. Seaton, Susan Meadows

EVIDENCE-BASED ANSWER The levels of cholesterol that should be treated for primary prevention are based on low-density lipoprotein cholesterol (LDL-C) levels of > 100 mg/dL to > 190 mg/dL and vary according to whether the patient's risk is high, moderate, or low. See the table to estimate risk. Grade of recommendation for medication indications: A (on the basis of high-quality randomized controlled trials). Grade of recommendation for lifestyle indications: B (on the basis of extrapolations from randomized controlled trials).

EVIDENCE SUMMARY Statins are the most effective at reducing LDL-C and the associated cardiovascular risk. The 5-year West of Scotland study (WOSCOPS) showed that a 26% reduction in LDL-C (from a mean of 192 to 142 mg/dL) using pravastatin 40 mg per day reduced the risk of either nonfatal myocardial infarction (MI) or coronary heart disease (CHD) death (number needed to treat [NNT] = 42; relative risk [RR] = 31; 95% confidence interval [CI],17 - 43). (1) This trial enrolled middle-aged men with an LDL-C level > 155 mg/dL without a history of prior MI, although subjects with stable angina (5% of the participants) were still eligible. Similar reductions were seen in cardiovascular death and in all-cause death (RR = 22; 95% CI = 0 - 40). Lovastatin reduced the risk of a first major acute coronary event (NNT = 24) in the 5-year AFCAPS/TexCAPS trial that enrolled 5608 men and 997 women with below-average high-density lipoprotein cholesterol (HDL-C) (men, 36 mg/dL; women, 40 mg/dL) without signs or symptoms of CHD. (2) LDL-C was lowered 25% (from a mean of 156 to 115 mg/dL). Unpublished results suggest that simvastatin may have a similar effect. Primary prevention data are still lacking for atorvastatin and fluvastatin.

The 7-year Lipid Research Clinics Coronary Prevention Trial (LRC-CPPT) documented a reduction in CHD death and/or nonfatal MI (NNT = 59) with a 12.6% reduction in LDL-C with the use of cholestyramine, a bile acid resin, 24 g per day. (3)

Results of studies of the fibric acid derivatives are mixed. Subjects taking gemfibrozil 1200 mg per day in the 5-year Helsinki Heart Study had fewer coronary events compared with those taking a placebo (NNT = 71). (4) Subsequent analysis suggests that patients with a high LDL-C/HDL-C ratio (> 5) plus hypertriglyceridemia ([greater than or equal to] 205 mg/dL) benefited the most. (5) Clofibrate is no longer used because of an unexplained increase in deaths in the WHO Cooperative Trial. (6) To date, outcomes in fenofibrate trials have only focused on surrogate markers and not long-term clinical outcomes.

RECOMMENDATIONS FROM OTHERS The recommendations of the Third Report of the National Cholesterol Education Program (7) (NCEP, Adult Treatment Panel III) are in the table. This report is an excellent source of additional information (http://www.nhlbi.nih.gov/guidelines/cholesterol/at p3xsum.pdf).

TABLE

Adult treatment recommendations from NCEP,
Adult Treatment Panel III

                                               LDL-C goal *
                                               at which to
                                                 consider
Risk category            LDL-C level            medication

Coronary heart disease   < 100 mg/dL          [greater than
risk equivalents                                or equal
                                              to] 130 mg/dl;
                                              [greater than
                                                or equal
                                            to] 100-129 mg/dL
                                                 optional

2 or more major risk     < 130 mg/dL             10-year
factors ([dagger])                        risk ([double dagger])
                                          10-20%: [greater than
                                        or equal to] 130 mg/dL;
                                                 10-year
                                              risk ([double
                                              dagger]) < 10%:
                                            [greater than or
                                           equal to] 160 mg/dL

0 or 1 major risk        < 160 mg/dL        [greater than or
factor ([dagger])                          equal to] 190 mg/dL;
                                              160-190 mg/dL
                                                 optional

NOTE: CHD risk equivalents include symptomatic carotid artery
disease, peripheral arterial disease, abdominal aortic
aneurysm, diabetes, and a 10-year risk of > 20%
(see ([double dagger]) below). The cut-off points for
therapy for patients with clinical CHD are the same as
for CHD risk equivalents.

* Initiate therapeutic lifestyle changes above these levels.

([dagger]) Major risk factors include cigarette smoking,
hypertension, HDL < 40 mg/dL, family history of
premature CHD (CHD in first-degree male relative < 55 y;
CHD in first-degree female relative < 65 y), age
(men [greater than or equal to] 45 y, women [greater
than or equal to] 55 y).

([double dagger]) To calculate 10-year
risk, use the Framingham Tables, available
at http://www.nhlbi.nih.gov/guidelines/cholesterol/risk_tbl.htm.

REFERENCES

(1.) Shepard J, Cobbe SM, Ford I, et al. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995; 333:1301-7.

(2.) Downs JR, Clearfield M, Weis S, et al. JAMA 1998; 279:1615-22.

(3.) The Lipid Research Clinics Coronary Primary Prevention Trial results. JAMA 1984; 251:351-64, 365-74.

(4.) Frick MH. Elo O, Happa K. et al. N Engl J Med 1987; 317:1237-45.

(5.) Manninen V, Tenkanen I, Koskinen P. et al. Circulation 1992; 85:37-45.

(6.) WHO cooperative trial. Lancet 1984; 2:600-4.

(7.) Executive Summary of the 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). JAMA 2001; 285:2486-97.

Terry L. Seaton, PharmD
St. Louis College of Pharmacy and
Mercy Family Medicine

Susan Meadows, MLS
University of Missouri--Columbia

Read a clinical commentary by David Switzer, MD, at www.fpin.org.