Thrombotic Events during Oral Anticoagulant Treatment: Results of the Inception-cohort, Prospective, Collaborative ISCOAT Study

Summary

The paper reports on rate and type of thrombotic events occurring during the observational, prospective, inception-cohort, multicenter ISCOAT study. 2,745 unselected, daily practice patients, consecutively referring to 34 Italian anticoagulation clinics to monitor the oral anticoagulant treatment, were included in the study from beginning of their first anticoagulant course. During a total follow-up of 2,011 patient-years of treatment 70 thrombotic events (3.5 per 100 patient years) were recorded in 67 patients: 20 fatal (1%), 39 major (1.9%) and 11 minor (0.6%). 34/70 events occurred within the first 90 days of treatment (relative risk - at multivariate analysis - of <90 days vs. >90 = 20.6, C.I. 12.7-33.5; p <0.0001). The risk was higher in patients aged >70 y (1.62, C.I. 1.0-2.61; p <0.05), and when indication for anticoagulant treatment was peripheral/cerebral arterial disease (1.84, C.I. 1.01-3.36; p <0.05). The frequency of thrombotic events was 17.5% when international normalised ratio (INR) levels were <1.5, decreasing to 2.3% for INRs within the 2-2.99 category (relative risk of INRs <2.0 vs. >2 = 1.88, C.1.1.16-3.07; p <0.05).

The recorded rate of thrombotic events was lower than that reported in the few available studies. A greater risk should be expected during the first 90 days of treatment, when anticoagulation levels are <2.0 INR, in patients > 70 years and in those with cerebrovascular/peripheral arterial disease.

• References

• 1 Hirsh J. Drug Therapy – Oral Anticoagulant Drugs. N Engl J Med 1991; 324: 1865-1875
• 2 Hirsh J, Fuster V. Guide to anticoagulant therapy Part 2: Oral Anticoagulants. Circulation 1995; 89: 1469-1480
• 3 Palareti G, Leali N, Coccheri S, Poggi M, Manotti C, D’Angelo A, Pengo V, Erba N, Moia M, Ciavarella N, Devoto G, Berrettini M, Musolesi S. on behalf of the ISCOAT (Italian Study on Complications of Oral Anticoagulant Therapy) Study Group. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective, collaborative study (ISCOAT). Lancet 1996; 348: 423-428
• 4 Landefeld CS, Beyth RJ. Anticoagulant-related bleeding – clinical epidemiology, prediction, and prevention. Am J Med 1993; 95: 315-328
• 5 van der, Meer FJM, Rosendaal FR, Vandenbroucke JP, Briet E. Bleeding complications in oral anticoagulant therapy – an analysis of risk factors. Archiv Intern Med 1993; 153: 1557-1562
• 6 Loeliger EA. Therapeutic Target Values in Oral Anticoagulation – Justification of Dutch Policy and a Warning Against the So-Called Moderate-Intensity Regimens. Ann Hematol 1992; 64: 60-65
• 7 Mariani G, Manotti C, Dettori AG. A computerized regulation of dosage in oral anticoagulant therapy. Res Clin Lab 1990; 20: 119-125
• 8 Tripodi A, Chantarangkul V, Akkawat B, Clerici M, Mannucci PM. A partial factor V deficiency in anticoagulated lyophilized plasmas has been identified as a cause of the international normalized ratio discrepancy in the external quality assessment scheme. Thromb Res 1995; 78: 283-292
• 9 Rosendaal FR, Cannegieter SC, Van der MeerFJM, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993; 69: 236-237
• 10 Kuller LH. Sudden death – definition and epidemiologic considerations. Prog Cardiovsc Dis 1980; 23: 01-12
• 11 Levine MN, Hirsh J, Landefeld S, Raskob G. Hemorrhagic complications of anticoagulant treatment. Chest 1992; 102: 352S-363S
• 12 Chamey R, Leddomado E, Rose DN, Fuster V. Anticoagulation clinics and the monitoring of anticoagulant therapy. Int J Cardiol 1988; 18: 197-206
• 13 Fihn SD, Mcdonell M, Martin D, Henikoff J, Vemmes D, Kent D, White RH. Risk factors for complications of chronic anticoagulation – a multicentre study. Ann Intern Med 1993; 118: 511-520
• 14 Gitter MJ, Jaeger TM, Petterson TM, Gersh BJ, Phil D, Silverstein MD. Bleeding and thromboembolism during anticoagulant therapy: a population-based study in Rochester, Minnesota. Mayo Clin Proceed 1995; 70: 725-733
• 15 Cannegieter SC, Rosendaal FR, Wintzen AR, Van der, Meer FJM, Vandenbroucke JP, Briet E. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 1995; 333: 11-17
• 16 Eckman MH, Levine HJ, Pauker SG. Effect of laboratory variation in the prothrombin-time ratio on the results of oral anticoagulant therapy. N Engl J Med 1993; 329: 696-702
• 17 Landefeld CS, Goldman L. Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy. Am J Med 1989; 87: 144-152
• 18 Levine M, Hirsh J. Hemorrhagic complications of long-term anticoagulant therapy for ischemic cerebral vascular disease. Stroke 1986; 17: 111-116
• 19 Dahl T, Abildgaard U, Sandset PM. Long-term anticoagulant therapy in cerebrovascular disease: does bleeding outweigh the benefit?. J Intern Med 1995; 237: 323-329
• 20 Cortelazzo S, Finazzi G, Viero P, Galli M, Remuzzi A, Parenzan L, Barbui T. Thrombotic and hemorrhagic complications in patients with mechanical heart valve prosthesis attending an anticoagulation clinic. Thromb Haemost 1993; 69: 316-320