Rationale and design features of a clinical trial examining the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT). SCAT Investigators.

BACKGROUND

In the treatment of coronary atherosclerotic artery disease (CAD), the mechanisms by which lipid lowering, a proven therapy, produces beneficial clinical effects remain unclear. Moreover, although potential mechanisms of benefit are well known and increasingly applied clinically, there are no conclusive data from clinical trials studying primarily the antiischemic effects of angiotensin-converting enzyme (ACE) inhibition in patients with normal heart function. The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT) is designed to clarify some of these issues in CAD patients with normal or mildly elevated cholesterol. DESIGN AND OBJECTIVES: SCAT is a three- to five-year, multicentre, randomized, double-blind, placebo controlled, 2 x 2 factorial trial evaluating the effects of cholesterol lowering therapy by simvastatin and/or ACE inhibition by enalapril on anatomic coronary atherosclerosis progression assessed by quantitative coronary angiography in CAD patients with preserved left ventricular function and total cholesterol levels between 4.1 and 6.2 mmol/L.

PATIENTS

Of 460 patients (age 61 +/- 9 years; 409 males, 51 females) enrolled between June 1991 and July 1995, 230 were randomized to simvastatin and 230 to placebo, and 229 to enalapril and 231 to placebo. Average baseline total cholesterol level was 5.20 +/- 0.61 mmol/L, high density lipoprotein cholesterol was 0.99 +/- 0.25 mmol/L, low density lipoprotein cholesterol was 3.36 +/- 0.57 mmol/L and triglycerides were 1.82 +/- 0.75 mmol/L. The trial will be completed in June 1998.

SIGNIFICANCE

Insights gained from this long term angiographic trial will lead to a better understanding of the mechanisms of benefits of these two treatments, both alone and in combination. Of particular interest is that this trial will be able to examine a suspected beneficial interaction, if present, between these two treatments.