Pravastatin potentiates the anticoagulant effects of low molecular weight heparin.
BACKGROUND
Statins have been shown in randomized trials to reduce coronary events independent of baseline LDL-C level. In the case of pravastatin sodium (PS), there is conflicting evidence as to what is the actual mechanism of its non-lipid lowering beneficial effects. Because pravastatin has been found to prolong the clotting time in vitro, we conducted a study to determine if pravastatin plus low molecular weight heparin (LMWH) would result in a synergistic effect on the in vitro clotting time, thus supporting the hypothesis that pravastatin exerts antithrombotic effects through reduction of fibrin formation.


METHODS
Aliquots of PS were combined with dalteparin, a LMWH, in 500 microl of human whole blood. The clotting time in seconds was analyzed on a Sonoclot Coagulation Analyzer, a miniviscometer that is sensitive to early fibrin generation.


RESULTS
PS and LMWH, each resulted in a significant prolongation of the clotting time compared with control. The combination of PS and LMWH resulted in a significantly prolonged clotting time compared with either given alone. All values were significantly different from each other (p<0.05). Our results showed that the combination of PS and a LMWH prolongs the clotting time to a significantly greater degree when compared to either administered alone.


CONCLUSIONS
The synergistic effect of PS and LMWH on prolongation of the clotting time suggests that PS exerts its effect by inhibition of the coagulation cascade and fibrin formation.
Zimmer
Jennifer E
JE
Department of Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, G-502 Medical Sciences Building, 185 South Orange Avenue, Newark, NJ 07102-2757, USA.
Spillert
Charles R
CR
Puppala
Sirisha
S
Zamecki
Katherine
K
Bhatt
Biren A
BA
Arora
Rohit R
RR
D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D002478:Cells, Cultured; D004338:Drug Combinations; D004357:Drug Synergism; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D017035:Pravastatin / Q000494:pharmacology*; D014914:Whole Blood Coagulation Time / Q000379:methods*
D000925:Anticoagulants; D004338:Drug Combinations; D006495:Heparin, Low-Molecular-Weight; D017035:Pravastatin