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CLINICAL STUDIES

Pravastatin therapy in hyperlipidemia: effects on thrombus formation and the systemic hemostatic profile

^a Cardiovascular Institute and the Departments of Medicine and Pathology, Mount Sinai School of Medicine, New York, New York, USA
^* Rogosin Institute, Cornell University Medical College, New York, New York, USA

Manuscript received June 12, 1998; revised manuscript received October 29, 1998, accepted January 5, 1999.

Reprint requests and correspondence: Dr. John A. Ambrose, Chief of Cardiology (Cronin 553), Saint Vincent’s Hospital and Medical Center, 153 West 11th Street, New York, New York 10011

OBJECTIVES

The study sought to determine the effects of lipid-lowering with pravastatin on the systemic fibrinolytic profile and on thrombus formation under dynamic flow conditions.

BACKGROUND

Lowering cholesterol (C) decreases clinical events in coronary artery disease (CAD) patients, but an analysis of the effects of lipid-lowering on the entire hemostatic and thrombotic profile has not been conducted.

METHODS

We prospectively studied 93 stable patients with untreated low-density lipoprotein cholesterol (LDL-C) >145 mg/dl. The CAD patients received pravastatin, and non-CAD patients were randomized to pravastatin versus placebo (double-blind). Thrombus formation upon an injured vascular surface was assessed in a substudy of 40 patients with a previously validated ex vivo perfusion chamber system. Systemic hemostatic markers and thrombus formation were evaluated at baseline, three and six months.

RESULTS

Placebo produced no changes in either the lipid profile, any of the hemostatic markers, or the ex vivo thrombus formation. Both pravastatin groups (CAD and non-CAD) showed decreased LDL-C by 30% within 6 weeks (188 to 126 mg/dl, p < 0.001 vs. baseline), and decreased plasminogen activator inhibitor-1 at 3- and 6-month follow-up compared to baseline (15% to 18% decrease at 3 months and 21% to 23% at 6 months). For the tissue plasminogen activator antigen, CAD and non-CAD groups showed significant decreases at 6 months compared to baseline (10% and 13%, respectively). No significant changes were observed with treatment in d-dimer, fibrinopeptide A, prothrombin fragment F_1.2, factor VIIa, von Willebrand factor, or C-reactive protein. Fibrinogen levels were significantly increased at 6 months compared to baseline, though still below the upper normal limit. In the perfusion chamber substudy, there was a decrease in thrombus area in non-CAD patients treated with pravastatin at both 3 and 6 months compared to baseline (by 21% and 34%, respectively). The CAD patients showed decreases in thrombus formation by 13% at 3 months, and by 16% at 6 months. The change in LDL-C- correlated modestly with the change in thrombus formation (r = 0.49; p < 0.01).

CONCLUSIONS

Pravastatin therapy significantly decreased thrombus formation and improved the fibrinolytic profile in patients with and without CAD. These early effects may, in part, explain the benefit rendered in primary and secondary prevention of CAD.

Abbreviations and Acronyms   ALT = alanine aminotransferase   AST = aspartate aminotransferase   CAD = coronary artery disease   CRP = C-reactive protein   HDL-C = high-density lipoprotein cholesterol   LDL-C = low-density lipoprotein cholesterol   PAI-1 = plasminogen activator inhibitor-1   t-PA = tissue plasminogen activator

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