Pravastatin: an antithrombotic effect independent of the cholesterol-lowering effect.
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 microm2 x 10(3) 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.
Dangas
G
G
Cardiovascular Institute, Mount Sinai Medical Center, Cardiovascular Research Foundation, New York, NY 10022, USA. gdangas@compuserve.com
Smith
D A
DA
Unger
A H
AH
Shao
J H
JH
Meraj
P
P
Fier
C
C
Cohen
A M
AM
Fallon
J T
JT
Badimon
J J
JJ
Ambrose
J A
JA
D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects*; D008078:Cholesterol, LDL / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D018056:Hemorheology; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use; D011446:Prospective Studies; D012307:Risk Factors; D010959:Tissue Plasminogen Activator / Q000032:analysis
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D017035:Pravastatin