Differential associations between lipid-lowering drugs, statins and fibrates, and venous thromboembolism: role of drug induced homocysteinemia?
BACKGROUND
Previous studies reported that statin use was associated with a decreased risk of venous thromboembolism (VTE), whereas no association was found between fibrate use and VTE. This report aims to test the hypothesis that part of these contrasting associations is related to total homocysteine level (tHcy).


METHODS
This report from a case-control study included 677 cases hospitalised with confirmed VTE and no major acquired risk factor of VTE and their 677 controls. Statin and fibrate exposure was defined as a current use of drugs at admission. Fasting serum tHcy was measured in all patients.


RESULTS
The estimated odds ratio for VTE related to statin use was 0.53 (CI 95% 0.37-0.78), whereas it was 1.88 (CI 95% 1.29-2.74) for fibrate use. No difference was found for tHcy levels between patients who were current users of statin compared to non users (17.7 micromol/L+/-7.3 in users vs 18.4 micromol/L+/-8.4 in non users, p=0.50). In contrast, fibrate users had a significant higher mean level of tHcy than non users (23.2 micromol/L+/-8.7 in users vs 18.4 micromol/L+/-8.4 in non users, p<0.0001). Nevertheless, adjustment on tHcy level did not alter significance and strength of the association between fibrates and VTE (1.66, CI 95% 1.07-2.59).


CONCLUSIONS
Statin use was associated with a significant decreased risk of VTE, whereas fibrate use was associated with a significant increased risk of VTE. This last association was independent of tHcy levels.
Brest University, GETBO EA 3878, EPI-PHARM, Brest, F-29609, France. karine.lacut@chu-brest.fr
Karine
K
Lacut
Grégoire
G
Le Gal
Jean-Hervé
JH
Abalain
Dominique
D
Mottier
Emmanuel
E
Oger
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002995:Clofibric Acid / Q000009:adverse effects*; D016208:Databases, Factual; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000453:epidemiology*; D000960:Hypolipidemic Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D011795:Surveys and Questionnaires; D054556:Venous Thromboembolism / Q000453:epidemiology*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D006710:Homocysteine; D002995:Clofibric Acid