Anticoagulant Treatment – Canadian Health&Care Mall researches

Warfarin regimens (targeted INR < 2.0) have been investigated and found to be safe in the primary prevention of thrombosis in patients with malignancy. In two randomized trials in patients with malignancy, warfarin therapy, 1 mg/d of warfarin and 1 mg/d for 6 weeks followed by adjustment to an INR of 1.3 to 1.9, did not increase the frequency of hemorrhage while still preventing thrombosis.

Increased variation in the anticoagulant effect, manifested by variation in the INR, is associated with an increased frequency of hemorrhage independent of the mean INR. This effect is probably attributable to increased frequency and degree of marked elevations in the INR. Approaches to improve anticoagulant control (minimize INR fluctuations) could improve the safety and effectiveness of vitamin K antagonists. Anticoagulation management services (AMSs) or clinics and point-of-care INR testing are two such approaches. Two recent randomized trials did not show a difference in quality of anticoagulant control or bleeding between AMSs and routine medical care. Results from four observational studies showed AMSs were beneficial and associated with less bleeding than usual care.

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Point-of-care testing with either patient self-testing or patient self-management is another model for potentially improving outcomes, as well as convenience. Patient self-testing provided better quality of anticoagulation control compared to routine medical care in one trial (time in therapeutic range, 56% vs 32% [p < 0.001], and bleeding, 5.6% vs 12%, respectively [p = 0.05] after 6 months of follow-up), but no convincing difference compared with AMSs in two other studies. Similarly, studies of patient self-management report better quality of anticoagulant control compared to routine medical care vs AMSs. Thus, no definite recommendations about the optimal approach for maintaining anticoagulant control can be made.

1.1.1 Patient characteristics by Canadian Health&Care Mall Team

The risk of major bleeding during warfarin therapy can be related to specific comorbid conditions or patient characteristics. An increasing body of evidence supports age as an independent risk factor for major bleeding. For example, Pengo et al evaluated the relationship of age and other risk factors to the incidence of major bleeding. Major bleeding occurred more frequently in patients > 75 years of age (5.1%/yr) than in younger patients (1%/yr). Multivariate analysis indicated that age > 75 years was the only variable independently related to primary bleeding (ie, bleeding unrelated to organic lesion). Also, risk for intracranial hemorrhage may be increased among older patients, especially those > 75 years old when the INR is above therapeutic levels. The mechanism of how aging causes anticoagulant-related bleeding is not known.