Optimale intensiteit van orale anticoagulantia voor de preventie van nieuwe ischemische complicaties en bloedingen na infra-inguïnale bypasschirurgie

The purpose of this study was to determine the optimal intensity of oral anticoagulants in patients who participated in a randomised trial of oral anticoagulants or aspirin after infrainguinal bypass graft surgery.

Design

Planned secondary data analysis.

Method

The distribution of the time spent in the therapeutic target area, distributed in international normalized ratio (INR) classes of 0.5 INR units, was calculated assuming a linear change between successive measurements. INR-specific incidence rates of ischaemic and haemorrhagic events were calculated as the ratio of the number of events in the different INR classes and the total patient-time spent in the classes concerned. The relationship between INR classes and the incidence of events was calculated with a Poisson regression model. The intensity of anticoagulation and the incidence of haemorrhages were also calculated for various age categories.

Results

A total of 41,928 INR measurements were recorded in 1326 patients (mean age: 69 years; 65 men) over a period of 1698 patient-years. Patients spent 50 of the total time within the target range of 3.0 to 4.4 INR. Most of the patient time (60) was spent between 2.5 and 3.9 INR. For each increasing class of 0.5 INR, the incidence of ischaemic events (n = 154, INR data on event available in 49 of cases) decreased by a factor of 0.97 (95-CI: 0.87-1.08). The incidence of major haemorrhages (n = 123, INR data on event available in 65 of cases) increased significantly by a factor of 1.27 (95-CI: 1.19-1.34) for each increasing 0.5 INR class. The optimal target range was 3.0 to 3.9 INR, with an incidence of 3.8 events (0.9 ischaemic and 2.9 haemorrhagic) per 100 patient-years. The proportion of patient-years spent within the target range increased somewhat with age, while the incidence of haemorrhages increased as well.

Conclusion

The target range of 3.0 to 3.9 INR was the optimal range of anticoagulation intensity achieved and was safe for preventing ischaemic events in patients after infrainguinal bypass graft surgery. Although age did not affect the accuracy of anticoagulation intensity, the risk of bleeding complications did increase with age.