Effect of niacin, warfarin, and antioxidant therapy on coagulation parameters in patients with peripheral arterial disease in the Arterial Disease Multiple Intervention Trial (ADMIT).
BACKGROUND
Patients with peripheral arterial disease (PAD) have high rates of cardiovascular morbidity and mortality, including that caused by associated coronary heart disease and cerebrovascular disease. Previous studies have shown that coagulation parameters are altered in PAD and that altered coagulation may play a critical role in the susceptibility to cardiovascular complications in PAD. It is therefore important to assess the effect of secondary prevention measures on coagulation in patients with PAD. The Arterial Disease Multiple Intervention Trial (ADMIT), a multicenter, randomized, placebo-controlled trial, was conducted to determine the feasibility of a combined lipid-modifying, antioxidant, and antithrombotic treatment regimen in patients with PAD. The objective of this study was to assess the effect of the ADMIT interventions on coagulation.


METHODS
ADMIT participants were randomly assigned to low-dose warfarin, niacin, and antioxidant vitamin cocktail or corresponding placebos in a 2 x 2 x 2 factorial design. Specialized coagulation studies were performed in a subset of 80 ADMIT participants at baseline and after 12 months of treatment.


RESULTS
Low-dose warfarin (1 to 4 mg/d) resulted in a significant decrease in factor VIIc (P <.001) and in plasma F1.2 (P =.001). Unexpectedly, niacin treatment also resulted in significant decrease in both fibrinogen (48 mg/dL; P <.001) and F1.2 (P =.04). von Willebrand factor increased after antioxidant vitamin treatment (P =.04).


CONCLUSIONS
A regimen of low-dose warfarin effectively modifies coagulation in patients with PAD. Niacin also favorably modifies fibrinogen and plasma F1.2. Niacin, in addition to its lipid effects, modifies abnormal coagulation factors that accompany PAD.
Chesney
C M
CM
Departments of Medicine and Pathology, University of Tennessee, Memphis, USA. cmchesney@aol.com
Elam
M B
MB
Herd
J A
JA
Davis
K B
KB
Garg
R
R
Hunninghake
D
D
Kennedy
J W
JW
Applegate
W B
WB
D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000188:drug therapy*; D001205:Ascorbic Acid / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008297:Male; D009525:Niacin / Q000627:therapeutic use*; D014810:Vitamin E / Q000627:therapeutic use; D014859:Warfarin / Q000627:therapeutic use*; D019207:beta Carotene / Q000627:therapeutic use; D014841:von Willebrand Factor / Q000378:metabolism
D000925:Anticoagulants; D000975:Antioxidants; D014841:von Willebrand Factor; D019207:beta Carotene; D014810:Vitamin E; D009525:Niacin; D014859:Warfarin; D005340:Fibrinogen; D001205:Ascorbic Acid