BLEEDING COMPLICATIONS OF ORAL ANTICOAGULANT TREATMENT - AN INCEPTION-COHORT, PROSPECTIVE COLLABORATIVE STUDY (ISCOAT)

Background Bleeding is the most serious complication of the use of ora l anticoagulation in the prevention and treatment of thromoboembolic c omplications. We studied the frequency of bleeding complications in ou tpatients treated routinely in anticoagulation clinics. Methods In a p rospective cohort from thirty-four Italian anticoagulation clinics, 27 45 consecutive patients were studied from the start of their oral anti coagulation (warfarin in 64%, acenocourmarol in the rest). The target anticoagulation-intensity was low (international normalised ratio [INR ] less than or equal to 2.8) in 71% of the patients and high (less tha n or equal to 2.8) in. the remainder. We recorded demographic details and the main indication for treatment and, every 3-4 months, INR and o utcome events. Such events included all complications (bleeding, throm bosis, other), although only overdosing. bleeding events are reported here, and deaths. We divided bleeding into major and minor categories. Findings 43% of the patients were women. Nearly three-fifths of the p atients were aged 60-79; 8% were over 80. The main indication for trea tment was venous thrombolism (33%), followed by non-ischaemic heart di sease (17%). Mean follow-up was 267 days. Over 2011 patient-years of f ollow-up, 153 bleeding complications occurred (7.6 per 100 patient-yea rs). 5 were fatal (all cerebral haemorrhages, 0.25 per 100 patient-yea rs), 23 were major (1.1), and 125 were minor (6.2). The rate of events was similar between sexes, coumarin type, size of enrolling centre, a nd target INR. The rate was higher in older patients: 10.5 per 100 pat ient-years in those aged 70 or over, 6.0 in those aged under 70 (relat ive risk 1.75, 95% CI 1.29-2.39, p<0.001). The rate was also higher wh en the indication was peripheral and/or cerebrovascular disease than v enous thromboembolism plus other indications (12.5 vs 6.0 per 100 pati ent-years) (1.80, 1.2-2.7, p<0.01), and during the first 90 days of tr eatment compared with later (11.0 vs 6.3, 1.75, 1.27-2.44, p<0.001). A fifth of the bleeding events occurred at low anticoagulation intensit y (INR<2, rate 7.7 per 100 patient-years of follow-up). The rates were 4.8, 9.5, 40.5, and 200 at INRs 2.9-2.9, 3-4.4, 4.5-6.9, and over 7, respectively (relative risks for INR>4.5, 7.91, 5.44-11.5, p<0.0001). Interpretation We saw fewer bleeding events than those recorded in oth er observational and experimental studies. Oral anticoagulation has be come safer in recent years, especially if monitored in anticoagulation clinics. Caution is required in elderly patients and anticoagulation intensity should be closely monitored to reduce periods of overdosing.