Pravastatin: An antithrombotic effect independent of the cholesterol-lowering effect

George Dangas, Donald A. Smith, Allen H. Unger, John H. Shao, Perwaiz Meraj, Carl Fier, Adam M. Cohen, John T. Fallon, Juan J. Badimon, John A. Ambrose

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

Lipid-lowering with statins reduces blood thrombogenicity. However, it is unknown whether this is purely due to LDL-cholesterol reduction, or it is related to a statin or agent specific effect. We investigated the relationship between reduction in blood thrombogenicity and the magnitude of low-density lipoprotein cholesterol (LDL-C) during pravastatin therapy. We prospectively followed for 6 months 57 hyperlipidemic patients who initiated therapy with pravastatin, and 36 patients who were randomized into placebo plus diet. Pravastatin-treated patients were grouped according to the LDL-C reduction at 6 months; (i) 'adequate LDL-C reduction': LDL-C reduction > 30% from baseline or LDL C < 125 mg/dl (n = 38; LDL-C reduction 74 ± 4 mg/dl; 6-month LDL-C 119 ± 5 mg/dl); (ii) 'inadequate LDL-C reduction': neither of the above criteria (n = 19; LDL-C reduction 31 ± 5 mg/dl; 6-month LDL-C 158 ± 6 mg/dl). Placebo patients were divided into those 'with LDL-C reduction' (n = 17, mean reduction 21 ± 5 mg/dl) and those 'without LDL reduction' (n = 19). The following parameters were altered at 6 months in both patients with 'adequate' and 'inadequate' LDL-C reduction: (1) tissue plasminogen activator decreased by 1.4 ± 0.4 and 1.5 ± 0.5 ng/ml respectively (p = NS); (2) plasminogen activator inhibitor-1 decreased by 8.7 ± 2.0 and 10.1 ± 2.7 ng/ml respectively (p = NS); (3) thrombus formation under dynamic flow conditions decreased by 3.5 ± 0.9 and 2.8 ± 1.2 μm2 x 103 respectively (p = NS). In contrast, no significant changes from baseline were noted in placebo-treated patients, regardless of their LDL-C reduction category; and multivariate analysis eliminated LDL-C reduction as an independent predictor of reduction in thrombogenicity. Therefore, the reduction in thrombogenicity was not proportional to the magnitude of LDL-C reduction suggesting that a class or agent specific property is primarily responsible for the pro-fibrinolytic/antithrombotic effects observed.

Original languageEnglish
Pages (from-to)688-692
Number of pages5
JournalThrombosis and Haemostasis
Volume83
Issue number5
DOIs
StatePublished - 2000

Keywords

  • Endothelium
  • Lipids
  • Platelet
  • Thrombus

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