In the Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC I)⁴ study, the effect of pravastatin therapy on coronary atherosclerosis was assessed by coronary angiography in patients with coronary disease and moderate hyper-cholesterolemia (baseline LDL-C range: 130-190 mg/dL). In this double-blind, multicenter, controlled clinical trial, angiograms were evaluated at baseline and at three years in 264 patients. Although the difference between pravastatin and placebo for the primary endpoint (per-patient change in mean coronary artery diameter) and one of two secondary endpoints (change in percent lumen diameter stenosis) did not reach statistical significance, for the secondary endpoint of change in minimum lumen diameter, statistically significant slowing of disease was seen in the pravastatin treatment group (p=0.02).

In the Regression Growth Evaluation Statin Study (REGRESS)⁵, the effect of pravastatin on coronary atherosclerosis was assessed by coronary angiography in 885 patients with angina pectoris, angiographically documented coronary artery disease and hypercholesterolemia (baseline total cholesterol range: 160-310 mg/dL). In this double-blind, multicenter, controlled clinical trial, angiograms were evaluated at baseline and at two years in 653 patients (323 treated with pravastatin). Progression of coronary atherosclerosis was significantly slowed in the pravastatin group as assessed by changes in mean segment diameter (p=0.037) and minimum obstruction diameter (p=0.001).

Analysis of pooled events from PLAC I, the Pravastatin, Lipids and Atherosclerosis in the Carotids Study (PLAC II)⁶, REGRESS, and the Kuopio Atherosclerosis Prevention Study (KAPS)⁷ (combined N=1891) showed that treatment with pravastatin was associated with a statistically significant reduction in the composite event rate of fatal and nonfatal myocardial infarction (46 events or 6.4% for placebo versus 21 events or 2.4% for pravastatin, p=0.001). The predominant effect of pravastatin was to reduce the rate of nonfatal myocardial infarction.

Primary Hypercholesterolemia (Fredrickson Type IIa and IIb)

PRAVACHOL (pravastatin sodium) is highly effective in reducing Total-C, LDL-C and triglycerides (TG) in patients with heterozygous familial, presumed familial combined and non-familial (non-FH) forms of primary hypercholesterolemia, and mixed dyslipidemia. A therapeutic response is seen within 1 week, and the maximum response usually is achieved within 4 weeks. This response is maintained during extended periods of therapy. In addition, PRAVACHOL is effective in reducing the risk of acute coronary events in hypercholesterolemic patients with and without previous myocardial infarction.

A single daily dose is as effective as the same total daily dose given twice a day. In multicenter, double-blind, placebo-controlled studies of patients with primary hypercholesterolemia, treatment with pravastatin in daily doses ranging from 10 mg to 40 mg consistently and significantly decreased Total-C, LDL-C, TG, and Total-C/HDL-C and LDL-C/HDL-C ratios (see Table 3).

In a pooled analysis of two multicenter, double-blind, placebo-controlled studies of patients with primary hypercholesterolemia, treatment with pravastatin at a daily dose of 80 mg (N=277) significantly decreased Total-C, LDL-C, and TG. The 25th and 75th percentile changes from baseline in LDL-C for pravastatin 80 mg were -43% and -30%. The efficacy results of the individual studies were consistent with the pooled data (see Table 3).

Treatment with PRAVACHOL modestly decreased VLDL-C and PRAVACHOL across all doses produced variable increases in HDL-C (see Table 3).

Table 3: Primary Hypercholesterolemia Studies: Dose Response of PRAVACHOL Once Daily Administration

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