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The National Heart, Lung and Blood Institute Type II Coronary Intervention Study - NHLBI
Description:
Cholestyramine for angiographic progression in CAD.
Hypothesis:
Lowering low-density lipoprotein (LDLc) cholesterol can arrest or retard the progression of CAD.
Study Design
Study Design:
Patients Screened: 143
Patients Enrolled: 116
NYHA Class: I = 82.8%
Mean Follow Up: 5 years
Mean Patient Age: 46
Female: 19
Mean Ejection Fraction: 34 pts = <55%
Patient Populations:
Elevated levels of LDL cholesterol
Angiographic evidence of CAD
Exclusions:
>75% luminal narrowing of the left main coronary artery
No coronary disease meeting the criteria of 20% luminal narrowing
Primary Endpoints:
CAD progression as measured angiographically, LDL cholesterol
Secondary Endpoints:
Percent of baseline lesions that progress, lesions that progress to occlusion, lesions that regress, size of lesion change, all cardiovascular endpoints.
Drug/Procedures Used:
Cholestyramine, 24 g/day
Principal Findings:
Diet alone reduced the low-density lipoprotein cholesterol 6% in both groups. After randomization, low-density lipoprotein cholesterol decreased another 5% in the placebo group and 26% in the cholestyramine-treated group.
Coronary angiography was performed in 116 patients before and after 5 years of treatment. CAD progressed in 49% (28 of 57) of the placebo-treated patients vs 32% (19 of 59) of the cholestyramine-treated patients (p less than .05). When only definite progression was considered, 35% (20 of 57) of the placebo-treated patients vs 25% (15 of 59) of the cholestyramine-treated patients exhibited definite progression; the difference was not statistically significant.
However, when this analysis was performed with adjustment for baseline inequalities of risk factors, effect of treatment was more pronounced. Of lesions causing 50% or greater stenosis at baseline, 33% of placebo-treated and 12% of cholestyramine-treated patients manifested lesion progression (p less than .05).
Similar analyses with other end points (percent of baseline lesions that progressed, lesions that progressed to occlusion, lesions that regressed, size of lesion change, and all cardiovascular end points) all favored the cholestyramine-treated group, but were not statistically significant.
Significant decrease in total cholesterol (TC) and low-density lipoprotein cholesterol (LDLc) and increases in high-density lipoprotein cholesterol (HDLc), as well as in HDLc/TC and HDLc/LDLc ratios, were observed with cholestyramine.
HDLc change was due to increase in HDL2A and HDL2B.
When the relationship between CAD progression and lipid changes was examined independent of specific treatment group, a significant inverse relationship was found between progression at 5 years and the combination of an increase in HDLc and a decrease in LDLc; changes in HDLc/TC and HDLc/LDLc were the best predictors of CAD change. While the testing of these relationships independent of treatment group was not part of the initial study design, the trends were observed in both the placebo-treated and cholestyramine-treated groups. Moreover, with multivariate analysis, the effect of cholestyramine treatment on CAD progression was eliminated by adding changes in HDLc/TC to the regression model.
Interpretation:
Although the sample size does not allow a definitive conclusion to be drawn, this study suggests that cholestyramine treatment retards the rate of progression of CAD in patients with Type II hyperlipoproteinemia.
These findings support the hypothesis that increases in HDLc and decreases in TC (or LDLc) can prevent or delay CAD progression.
References:
1. Controlled Clinical Trials. 1982;3:91-111. Study design
2. Circulation 1984;69:313-24. Final results (clinical)
3. Circulation 1984;69:325-37. Final results (lipid levels)
Keywords: Cholestyramine Resin, Coronary Artery Disease, Multivariate Analysis, Cholesterol, LDL, Coronary Angiography, Hyperlipoproteinemia Type II, Socioeconomic Factors, Risk Factors, Cholesterol, HDL, Diet, Constriction, Pathologic
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