Principal Findings:

Pravastatin, 40 mg/d decreased total cholesterol levels by 22%, decreased LDL cholesterol by 32%, decreased triglyceride levels by 15%, and increased HDL cholesterol levels by 8% (P <0.001 for all comparisons). Pravastatin also decreased the ratio of total cholesterol to HDL cholesterol by 28% (P <0.001) and the ratio of LDL cholesterol to HDL cholesterol by 37% (P <0.001).

Nicotinic acid, 1.5 g/d, was added to pravastatin for 40 of 44 patients in the control group. Nicotinic acid caused additional mean reductions of 6% in total cholesterol levels (P <0.002), and 10% in triglyceride levels (P <0.001), and it caused an additional increase in HDL cholesterol levels of 8% (P <0.001). Nicotinic acid (1.5 g/d) and pravastatin (40 mg/d) combined produced changes of -26% in total cholesterol levels, -39% in LDL cholesterol levels, -23% in triglyceride levels, +17% in HDL cholesterol levels, -33% in the ratio of total cholesterol to HDL cholesterol, and -46% in the ratio of LDL cholesterol to HDL cholesterol (P <0.001 for all comparisons).

When the dose of nicotinic acid was increased to 2.25 to 3 g/d in combination with pravastatin in 23 patients, further reductions were seen. Total cholesterol levels were reduced by an additional 7% (P = 0.007), LDL cholesterol levels were reduced by an additional 14% (P <0.001), and triglyceride levels were reduced by an additional 13% (P = 0.03). Levels of HDL cholesterol increased by an additional 6% (P = 0.02). The total effect of nicotinic acid (2.25 to 3 g/d) and pravastatin (40 mg/d) combined produced changes of -29% in total cholesterol levels, -44% in LDL cholesterol levels, -26% in triglyceride levels, +20% in HDL cholesterol levels, -41% in the ratio of total cholesterol to HDL cholesterol, and -53% in the ratio of LDL cholesterol to HDL cholesterol (P <0.001 for all comparisons).

Cholestyramine, 4 to 24 g, was added to pravastatin and nicotinic acid in 21 patients. Surprisingly, the addition of this resin partially reversed the action of the previous steps. The mean triglyceride level increased by 46% (P <0.001), and the mean HDL cholesterol level decreased by 8% (P = 0.03) relative to the levels achieved at the previous step (nicotinic acid, to 3 g/d in combination with pravastatin, 40 mg/d). The LDL cholesterol level did not change.

Twelve patients required gemfibrozil, 600 to 1200 mg/d. In contrast to the lack of overall benefit produced by the addition of cholestyramine, the addition of gemfibrozil increased HDL cholesterol levels by 12% (P = 0.03). Triglyceride levels markedly decreased by 37% (P <0.001) relative to the levels achieved at the previous step. LDL cholesterol level increased by 12% (P = 0.09).
There was no significant difference in coronary atherosclerosis during follow-up between the active treatment group and placebo groups: the mean minimum diameter narrowed significantly, but to the same extent in both groups (change baseline to 2.5 years 0.14 [SD 0.42] and 0.15 [SD 0.41] mm, respectively, both p <0.001). Similarly, the change in percentage stenosis did not differ between the groups (2.1 [SD 10.6] vs. 2.4 [SD 10.3] %). By multiple regression analysis, the adjusted difference between the groups was 0.04 mm (95% CI, -0.04 to 0.12 mm) increase in minimum diameter and a 0% (-1.7 to 1.7) change in percentage stenosis. The groups differed significantly in plasma lipids (% change in active minus % change in placebo group: -28% total cholesterol, -41% LDL-cholesterol, 13% HDL-cholesterol, -26% triglycerides, -31% apolipoprotein B, all p <0.001).