CCAIT (Canadian Coronary Atherosclerosis Intervention Trial)

18 Mar, 14

CCAIT (Canadian Coronary Atherosclerosis Intervention Trial)

Effects of monotherapy with an HMG-CoA reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography. The Canadian Coronary Atherosclerosis Intervention Trial.

Purpose

To evaluate whether lovastatin (a HMG-CoA reductase inhibitor) therapy will affect coronary atherosclerosis as assessed by serial quantitative coronary angiography.

Design

Randomized, double-blind, placebo controlled, multicenter.

Patients

331 patients (81% men), 27-70 years old, with angiographically proven diffuse coronary artery disease, total serum cholesterol 220-300 mg/dL, and serum triglycerides <500 mg/dL. Women with child bearing potential and patients with previous coronary artery bypass surgery; previous coronary angioplasty within 6 months; ejection fraction <40%; left main coronary artery stenosis >50%; 3 vessel disease with proximal LAD stenosis >70%; coexisting severe illness; myocardial infarction or unstable angina within 6 weeks prior to randomization; concurrent use of lipid lowering drugs, corticosteroids, anticoagulants, cimetidine, or cyclosporine; liver function disturbances; or renal failure were excluded.

Follow-up

Clinical follow-up for 24 months. Coronary angiography at baseline and 24 months.

Treatment Regimen

Randomization to lovastatin 20 mg/d (n=165) or placebo (n=166). The dose was increased to 40 mg/d in patients whose LDL cholesterol was > 130 mg/dL despite 4 weeks of therapy. If LDL cholesterol was still >130 mg/dL, the dose was increased to 80 mg/d.

Additional Therapy

AHA phase I diet. Aspirin 325 mg on alternate days. Revascularization (CABG or PTCA) was not permitted during the 24 month study period.

Results

The target LDL cholesterol - 130 mg/dL was achieved by 69% of the lovastatin and 10% of the placebo- treated patients. Total cholesterol reduced by 21 11% (p <0.001), LDL cholesterol reduced by 29 11% (p <0.001), HDL cholesterol increased by 7.3 19% (p <0.001), and apolipoprotein B decreased by 21 12% (p <0.001) in the lovastatin - assigned patients.
Angina class improved by 1 grade in 50 lovastatin and 43 placebo patients, and worsened by 1 grade in 23 lovastatin and 27 placebo patients (p=0.087).
There was a trend toward less coronary events in the lovastatin group (14 vs 18 patients had 1 event) that was not statistically significant.
Coronary change score [defined as the per patient mean of the minimum lumen diameter changes (follow-up minus baseline angiogram) for all lesions measured, excluding those with <25% stenosis on both films] worsened by 0.09 0.16 mm in the placebo group and by 0.05 0.13 mm in the lovastatin group (p=0.01).
Mean percent diameter stenosis increased by 2.89 5.59% in the placebo group and by 1.66 4.5% in the lovastatin group (p=0.039).
Progression (a decrease in minimum lumen diameter of 1 lesion by 0.4 mm) with no regression at other coronary segments was observed in 33% of the lovastatin vs 50% of the placebo group (p=0.003). 6.8% vs 9.4% of the lesions in the lovastatin and placebo treated patients progressed, respectively (p=0.017), 15% diameter stenosis progression was noted in 5.9% and 9.6% of the lesions in the lovastatin and placebo treated patients, respectively p=0.008). Progression to a new total occlusion was noticed in 1.6% of the lovastatin group vs 1.9% of the placebo group.
New coronary lesions were detected in 16% of the lovastatin vs 32% of the placebo group (p=0.001).
Lovastatin was equally effective in men and women.

Conclusion

Lovastatin slowed the progression of coronary atherosclerotic lesions and inhibited the formation of new coronary stenotic lesions.

Circulation 1994;89:959-68