Atorvastatin reduces thrombin generation after percutaneous coronary intervention independent of soluble tissue factor.
BACKGROUND
Statins were previously shown to suppress cellular tissue factor (TF) in vitro. Here, we investigated the effect of atorvastatin on the TF-pathway and thrombin generation after coronary angioplasty and stenting in vivo.


METHODS
A cohort of 30 patients with coronary artery disease (CAD) was randomised to treatment with either none (n=10), 10 mg (n=10) or 80 mg (n=10) atorvastatin per day for the postinterventional period of 6 months starting the day before percutaneous coronary intervention (PCI). Fasting blood samples were collected on admission and after 6 weeks and 6 months of statin therapy to determine sTF, free tissue factor pathway inhibitor (TFPI) and prothrombin fragment F1.2 by immunoassay.


RESULTS
Soluble TF (sTF) significantly correlated with thrombin generation as measured by prothrombin fragment F1.2 at baseline. This correlation was lost 6 weeks and 6 months after initiation of statin therapy. In vivo, F1.2 was significantly lowered after 6 months of statin therapy by both, low dose (0 vs. 10 mg: 1.3+/-0.3 vs. 0.7+/-0.2 ng/ml; P<0.05) and high dose (0 vs. 80 mg: 1.2+/-0.3 vs. 0.6+/-0.2 ng/ml; P=0.01) atorvastatin compared to control. However, sTF and free TFPI did not change significantly with atorvastatin therapy when compared to baseline or control.


CONCLUSIONS
Our results demonstrate reduced in vivo generation of thrombin six months after percutaneous coronary intervention and statin therapy independent of sTF and free TFPI.
Bartok
Andrea
A
2nd Department of Medicine, Division of Angiology, Medical University of Vienna, Vienna, Austria, Währinger Gürtel 18-20, A-1090 Wien, Austria.
Steiner
Sabine
S
Seidinger
Daniela
D
Jetzl
Angelika
A
Huber
Kurt
K
Minar
Erich
E
Stefenelli
Thomas
T
Kopp
Christoph W
CW
D015906:Angioplasty, Balloon, Coronary; D000925:Anticoagulants / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin; D015331:Cohort Studies; D003327:Coronary Disease / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011516:Prothrombin / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D013917:Thrombin / Q000096:biosynthesis* / Q000187:drug effects; D013925:Thromboplastin / Q000187:drug effects / Q000378:metabolism*; D016896:Treatment Outcome
D000925:Anticoagulants; D006538:Heptanoic Acids; D008055:Lipids; D008074:Lipoproteins; D011758:Pyrroles; C051928:lipoprotein-associated coagulation inhibitor; D011516:Prothrombin; D013925:Thromboplastin; D000069059:Atorvastatin; D013917:Thrombin