Effects of One Year of Treatment with Pravastatin, an HMG‐CoA Reductase Inhibitor, on Lipoprotein a

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Abstract
Lipoprotein a [Lp(a)] has emerged as a critical factor in the assessment of cardiovascular risk. In the study reported here, Lp(a) concentrations were monitored in patients taking pravastatin, a new hydrophilic, HMG‐CoA reductase inhibitor. A cohort of patients with frozen plasma aliquots at baseline, week 12 of the double‐blind therapy, and week 48 of open‐label therapy (1 year's treatment) was selected from 306 participants in a phase 2 dose‐ranging study of pravastatin. The 125 men and women in the cohort had mean low‐density lipoprotein cholesterol (LDL‐C) concentrations of at least 150 mg/dL (3.88 mmol/L), and mean plasma triglyceride concentrations less than 250 mg/dL (2.82 mmol/L) during the baseline diet phase. During the double‐blind phase, 46 patients received placebo, and 79 received pravastatin 10, 20, or 40 mg daily. Only the 79 pravastatin‐treated patients in the cohort continued in the 48‐week open‐label study of pravastatin. During the double‐blind phase, Lp(a) decreased 4.6% in patients taking placebo, and 0.4% in patients taking pravastatin. Net change was not significant. At week 48, in the patients taking pravastatin, Lp(a) had increased 2.4%, a difference that again was not statistically significant. Low‐density lipoprotein cholesterol (‐33.6%), total cholesterol (‐25.6%), triglycerides (‐19.9%), high‐density lipoprotein cholesterol (HDL‐C) (+7.0%), apolipoprotein A‐I (+13.3%), and apolipoprotein B (‐33.0%) changed significantly (P < .01). Among 19 patients with baseline Lp(a) levels greater than 30 mg/dL, Lp(a) decreased insignificantly. Optimal pharmacologic therapy for patients with elevated total cholesterol and LDL‐C should lower total cholesterol and LDL‐C concentrations with beneficial or no adverse effects on other lipoprotein fractions. Pravastatin did not significantly affect Lp(a) concentrations, even in those patients with Lp(a) greater than 30 mg/dL at baseline and significantly elevated HDL‐C (P < 0.001).