Long-term effects of cholesterol lowering and angiotension-converting enzyme inhibition on coronary atherosclerosis. The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT). - SCAT

Description:

Long-term effects of cholesterol lowering and angiotension-converting enzyme inhibition on coronary atherosclerosis. The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT).

Hypothesis:

This study assessed the effects of a statin, an ACE inhibitor, and the combination on the natural history of angiographic coronary disease in patients without hypercholesterolemia.

Study Design

Study Design:

Patients Enrolled: 460

Primary Endpoints:

Change in coronary luminal diameter and maximal percent stenosis measured by quantitative coronary arteriography and clinical events.

Drug/Procedures Used:

460 patients were randomized with a 2 x 2 factorial design to receive up to 40mg of simvastatin, enalapril 10mg bid, the combination, or matching placebos and followed for an average of 4 years. Mean baseline cholesterol was 200 mg/dl, triglycerides 160 mg/dl, HDL-C 38 mg/dl, and LDL-C 129 mg/dl.

Principal Findings:

Average age was 60, M/F = 9, 15% were current smokers, 35% hypertensive, >50% had angina and 70% a previous MI, 90% were on ASA, 48% beta blockers, and 65% nitrates. 394 of the 460 subjects had paired angiograms. The average per-patient mean diameter decreased by 0.07 ± 0.20 mm with simvastatin compared to a decrease of 0.14 ± 0.25 mm (P=0.004) with placebo. The average increase in maximum percent diameter stenosis with simvastatin was 1.67 ± 5.01% and with placebo 3.83 ± 6.58% (P=0.0003). There was a relationship between lipid lowering (30% reduction in LDL-C) and angiographic benefit. There was no benefit attributable to enalapril with or without simvastatin on QCA endpoints. Simvastatin treated patients had less need for CABG/PTCA (13 vs. 28, P=0.02), and fewer enalapril patients had a combined endpoint of death/MI/CVA (16 vs. 30, P=0.043), with no added benefit of combination therapy.

This trial extends the observation of the beneficial angiographic effects of lipid lowering therapy to normocholesterolemic patients. The implications of the neutral effects of ACE inhibition is uncertain, but deserve further investigation in light of the positive clinical benefits in this study and the HOPE trial.

Interpretation:

The findings are similar to PLAC-1 (pravastatin in normocholesterolemia and CAD) The unique finding is that in spite of a 4 year follow-up enalapril had no effect on angiographic coronary disease progression. Yet, as in HOPE a relatively small number of patients was needed to demonstrate a clinical benefit. Further tria data is needed to ascertain the clinical benefits of adding ACE inhibitors to statin therapy in CAD.

References:

1. Teo K, Burton JR, Buller CE, et al, for the SCAT Investigators. Circulation. 2000;102:1748-54.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Atherosclerotic Disease (CAD/PAD), Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Coronary Artery Disease, Enalapril, Follow-Up Studies, Hyperlipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Constriction, Pathologic, Simvastatin, Cholesterol, Coronary Angiography, Nitrates, Pravastatin, Triglycerides, Disease Progression


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