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

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).