Air Force Texas Coronary Atherosclerosis Prevention Study - AFCAPS/TEXCAPS

Description:

Lovastatin vs. placebo for primary prevention of CAD events.

Hypothesis:

Whether reduction of LDL cholesterol is the appropriate treatment for persons with "average" LDL levels or whether treatment is best reserved for patients with the additional risk of below average high-density lipoprotein (HDL) levels.

Study Design

Study Design:

Patients Screened: 102,800
Patients Enrolled: 6,605
Mean Follow Up: 5.1 years
Mean Patient Age: 58
Female: 15

Patient Populations:

At least 1 risk factor for ischemic cardiovascular disease
Men (age ≥45) and women (age ≥55) up to 73 years of age
HDL <50 mg/dL
LDL between 130 - 190 mg/dL or 125 - 129 mg/dL if the TC to HDL cholesterol ratio is >6.

Exclusions:

Clinical evidence of ischemic cardiovascular disease
Uncontrolled hypertension
Secondary hyperlipidemia
Type 1 or type 2 diabetes mellitus that was either managed with insulin or associated with a glycohemoglobin level of at least 10% (20% above the upper limit of normal).
Body weight of more than 50% greater than the desirable limit for height according to the 1983 Metropolitan Life Insurance tables.

Primary Endpoints:

Composite of fatal or nonfatal MI, unstable angina, or sudden cardiac death

Secondary Endpoints:

Fatal or nonfatal coronary revascularization procedures
Unstable angina
Fatal or nonfatal myocardial infarction
Fatal or nonfatal cardiovascular events
Fatal or nonfatal coronary events
Cardiovascular mortality
CHD mortality.

Tertiary:
Noncardiovascular mortality (with subset analyses for unintentional or violent death and death from cancer)
Fatal and nonfatal cancer (excluding basal cell and squamous cell skin cancers)
Discontinuation of medication because of adverse drug effects.

Drug/Procedures Used:

Lovastatin 20 mg or placebo; up-titration to 40 mg (2 doses lovastatin or 2 doses placebo) at 18 weeks if LDL goal (≤110 mg/dL) had not been achieved.

Principal Findings:

At 12 months, lovastatin therapy was associated with an 18.4% reduction in total cholesterol (TC), a 25% reduction in LDL, a 6% increase in HDL, and a decrease in triglycerides of 15%. There also were improvements in the ratio of TC to HDL (-21.8%) and LDL to HDL (-28%). All changes in lipid parameters were significant compared to placebo (p<0.001).

Despite the low-risk population studied, lipid-lowering therapy produced a 37% reduction in the primary endpoint of fatal or nonfatal MI, unstable angina, or sudden cardiac death.

Among the 17% of participants who met NCEP guidelines for treatment, the relative risk reduction was 47% (p=0.006) compared to 33% (p=0.003) in the rest of the active therapy study group.

Benefit was consistent across the tertiles of LDL and HDL studied.

Among men receiving lovastatin, there was a 37% reduction in the primary endpoint for an absolute risk reduction of 2.2%; the number needed to treat over 5 years to prevent 1 event was 46. Among the women on lovastatin, there were 20 primary endpoint events, 7 in the lovastatin group and 13 in the placebo group, for a relative risk reduction of 46%. However, due to the size of the subgroup and the small number of primary endpoint events, this difference did not reach statistical significance. Among women there was an absolute risk reduction of 1.2%; with the number needed to treat over 5 years to prevent 1 event at 88. There were no statistically significant differences in effect between genders.

Men receiving lovastatin, had a higher rate of drug-related adverse events compared to men receiving placebo (18% versus 16%, p=0.048), mostly due to changes in liver function tests. Breast cancer was reported in 13 lovastatin and 9 placebo-treated women (p=0.0519).

A larger and statistically significant reduction in the primary endpoint was seen in the subset of patients <65 years of age (42%, p<0.001). However, because of more events overall in the elderly cohort, the number of patients needed to treat to prevent 1 event was 47 in the elderly group compared to 50 in the younger treated patients.

Interpretation:

This was the first primary prevention study to include a sizable group of women (15%) and older adults (21% age ≥65 years). Based on current National Cholesterol Education Program (NCEP) guidelines, 32% of participants would not have been recommended for a fasting lipid profile and 83% would not have been recommended for any cholesterol-lowering therapy. Participants with HDL ≤40 mg/dL received the greatest benefit, suggesting that current recommendations for treatment at HDL ≤35 mg/dL may need to be reconsidered.

References:

1. Am J Cardiol 1997;80:287-93 Design and rationale
2. JAMA 1998; 279:1615-22 Final results
3. Circulation 1998; 98(Suppl I):I-46 Gender subgroups
4. Circulation 1998; 98(Suppl I):I-46 Elderly subgroups

Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, SCD/Ventricular Arrhythmias, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Diet

Keywords: Coronary Artery Disease, Lovastatin, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Breast Neoplasms, Risk Factors, Primary Prevention, Liver Function Tests, Cholesterol, Hypolipidemic Agents, Triglycerides, Fasting, Death, Sudden, Cardiac


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