Changes in levels of factor VII and protein S after acute myocardial infarction: effects of low-dose warfarin.
Persistent coagulation activity after an acute myocardial infarction may increase the risk of reinfarction. We prospectively investigated the effects on plasma coagulation of a low, fixed dose of warfarin in combination with aspirin after myocardial infarction. We also evaluated the influence of coagulation activity on clinical outcome. Plasma samples from 97 patients, randomised to 1.25 mg of warfarin daily in combination with 75 mg of aspirin or aspirin alone were drawn 4 days, 1 month, and 6 months after myocardial infarction. Patients receiving warfarin had a greater reduction in factor VII coagulation activity (FVII:C) after 6 months: 0.18 vs. 0.06 U/mL,(95% CI, 0.02-0.22), whereas no differences were seen in levels of protein C, protein S, or prothrombin fragment 1+2. In the acute phase, the level of free protein S was lower than after 6 months in both groups: 25.6 vs. 28.8% (95% CI, 4.19--2.35). Cardiovascular mortality, reinfarction, and stroke were evaluated after 4 years (median). In a survival analysis, every 0.1 U/mL increase in the level of FVII:C1 month after myocardial infarction was associated with an 15% increase in risk of cardiovascular events (95% C1, 1.01-1.30). Warfarin at 1.25 mg daily reduces FVII:C but not systemic thrombin generation measured as prothrombin fragment 1 +2. Low levels of the anticoagulant protein S may contribute to a procoagulant state.
Holm
J
J
Department of Cardiology, Malmö University Hospital, Sweden. johan.holm@medforsk.mas.lu.se
Hillarp
A
A
Erhardt
L
L
Berntorp
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000941:Antigens / Q000032:analysis*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002545:Brain Ischemia / Q000453:epidemiology; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005167:Factor VII / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D010446:Peptide Fragments / Q000032:analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011486:Protein C / Q000032:analysis; D017293:Protein S / Q000032:analysis*; D011516:Prothrombin / Q000032:analysis; D012008:Recurrence; D012306:Risk; D016037:Single-Blind Method; D015912:Thrombolytic Therapy; D019851:Thrombophilia / Q000097:blood / Q000150:complications; D013988:Ticlopidine / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000925:Anticoagulants; D000941:Antigens; D010446:Peptide Fragments; D011486:Protein C; D017293:Protein S; C042580:factor VII clotting antigen; C045879:prothrombin fragment 1.2; D014859:Warfarin; D005167:Factor VII; D011516:Prothrombin; D013988:Ticlopidine; D001241:Aspirin