Lowering LDL Cholesterol in Patients with Severe Coronary Disease

Abstracts & Commentary

Synopsis: Statins should be given to all hyperlipidemic patients early during acute ischemic syndromes and physicians should not withhold statin therapy in women or the elderly.

Sources: Dupuis J, et al. Circulation 1999;99:3227-3233; Waters D. Circulation 1999;99:3215-3217; Campeau L, et al. Circulation 1999;99:3241-3247.

Two recent studies support the use of a statin in patients with severe coronary artery disease. The Montreal Heart Institute reported the RECIFE Trial, which demonstrated in a small placebo-controlled cohort of acute myocardial infarction or unstable angina patients with elevated cholesterol, that six weeks of pravastatin therapy (30 mg/d) improved endothelial function, as assessed by serial brachial artery ultrasound flow-mediated dilatation (FMD). Total and LDL baseline cholesterol levels were similar in both groups; cholesterol decreased with pravastatin, but not placebo. FMD, initially comparable between the two groups, was unchanged at six weeks with placebo, but increased by approximately 40% in the pravastatin cohort. Clinical events were not reported. Thrombostatic measurements of endothelial and other platelet products were assessed. Platelet activation and an enhanced thrombogenic state was observed in both groups at baseline, improving almost to normal by six weeks, with no difference between pravastatin and placebo. Dupuis and colleagues conclude that a statin should be given to all patients early during acute ischemic syndromes, such as unstable angina or myocardial infarction, if baseline total or LDL cholesterol are elevated. Blood lipids were drawn on admission; baseline total cholesterol was 243 mg/dL and LDL 160 mg/dL. Dupuis et al suggest that the rapid improvement of endothelial function at six weeks should result in important clinical benefits, short and long term, and state that delays in initiating statin therapy in hyperlipidemic patients admitted to a coronary care unit are not justified. They acknowledge that it remains unclear as to whether improvement in FMD/endothelial function can be interpreted as a surrogate for subsequent clinical benefits, as have been shown by large secondary prevention trials in chronic CAD patients.

An updated report from the post-CABG trial confirms that aggressive LDL cholesterol lowering is equally beneficial in the elderly, women, and individuals with a variety of risk factors, including low HDL and high triglycerides, smoking, and diabetes. The improvements in angiographic status of the bypass grafts were comparable in all patients who received aggressive LDL lowering, regardless of baseline CAD risk profile (individuals received 80 mg of lovastatin for 4-5 years). Conversely, in the moderate LDL cholesterol lowering group (2½-5.5 mg of lovastatin per day), baseline CAD risk factors predicted a more adverse angiographic outcome. In the high-dose lovastatin cohort, the statin resulted in LDL levels of less than 93-97 mg/dL, which completely eliminated the adverse graft and outcomes associated with multiple CAD risk factors. Dupuis et al conclude that physicians should not withhold statin therapy in women or the elderly. They suggest that an isolated elevation of LDL cholesterol in the absence of other risk factors may not impart as much hazard as a less elevated cholesterol associated with multiple risk factors, and that major benefits will accrue to those individuals in the latter category with aggressive LDL lowering. A target LDL cholesterol of less than 100 should be sought for all post-CABG patients, regardless of age or sex.

Comment by Jonathan Abrams, MD

These two studies enhance the database supporting aggressive lowering of LDL cholesterol. While neither provides clinical end point data (because of small sample size), the endothelial function improvement and reduction in angiographic graft progression with statins should ultimately be beneficial in these patients with CAD by decreasing morbidity and mortality. In an accompanianing editorial, Waters also recommends that physicians should not delay initiating lipid-lowering therapy in patients who are admitted with an acute coronary syndrome. He emphasizes abnormal platelet-thrombogenic factors improvement related to the benefits of LDL cholesterol lowering; in spite of the absence of clinical trial data in unstable angina or recent infarction patients, starting cholesterol lowering therapy at the time of an acute coronary syndrome can now be justified, but only on the basis of the clear, long-term benefit documented in stable coronary patients.’ Thus, a statin should be considered as part of early discharge therapy for virtually all patients admitted for acute ischemic syndromes unless the baseline lipid levels are documented to be low normal, with LDL cholesterol close to 100 mg/dL on the initial blood draw.

LDL cholesterol lowering with a statin has been shown to:

a. increase flow-mediated vasodilation.

b. reduce the thrombogenic state.

c. improve the angiographic appearance of coronary bypass grafts.

d. a and c