title: Gemfibrozil reduces plasma prothrombin fragment F1 + 2 concentration, a marker of coagulability, in patients with coronary heart disease.
abstract: The effects of gemfibrozil on several indices of haemostatic activity were explored in male patients with coronary heart disease (CHD). Sixty-three of 71 patients completed a crossover study in which gemfibrozil 1,200 mg/day and matching placebo were each taken in randomised order for 2 months in a double-blind manner, separated by a 2-month washout period. Serum cholesterol decreased by an average (95% confidence interval) of 12 (9 to 15)% and non-fasting triglyceride concentration by 43 (34 to 51)% during active treatment. Plasma prothrombin fragment F1 + 2 concentration, a marker of the in vivo rate of generation of thrombin, was 25 (12 to 37)% lower on average while on gemfibrozil than during the placebo phase. Factor VII coagulant activity (VIIc) and antigen concentration, and fibrinopeptide A concentration were not influenced by gemfibrozil in the group overall. However, the VIIc response appeared to be dependent upon the untreated cholesterol level. Hypercholesterolaemic men (cholesterol greater than 6.5 mmol/l) experienced a significant reduction in VIIc averaging 6% of standard during active therapy. Other effects of gemfibrozil were a 5 (2 to 9)% increase in plasma fibrinogen by a gravimetric method, an 11 (8 to 13)% increase in platelet count, and a 6 (2 to 10)% reduction in white cell count. The reduced incidence of CHD following gemfibrozil therapy in hyperlipidaemic patients may arise in part through a reduction in procoagulant activity and thus the risk of an occlusive coronary thrombosis.
authors.affiliation: MRC Epidemiology and Medical Care Unit, Northwick Park Hospital, Harrow, UK.
authors.forename: H C
authors.initials: HC
authors.lastname: Wilkes
authors.forename: T W
authors.initials: TW
authors.lastname: Meade
authors.forename: S
authors.initials: S
authors.lastname: Barzegar
authors.forename: A J
authors.initials: AJ
authors.lastname: Foley
authors.forename: L O
authors.initials: LO
authors.lastname: Hughes
authors.forename: K A
authors.initials: KA
authors.lastname: Bauer
authors.forename: R D
authors.initials: RD
authors.lastname: Rosenberg
authors.forename: G J
authors.initials: GJ
authors.lastname: Miller
mesh_terms: D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000502:physiology*; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D015248:Gemfibrozil / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010349:Patient Compliance; D010446:Peptide Fragments / Q000378:metabolism*; D011516:Prothrombin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D015248:Gemfibrozil