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Background— Vitamin K antagonist (VKA) therapy is increasingly being used for the prevention of venous thromboembolism and stroke in atrial fibrillation. Bleeds are the major concern for VKA prescription, especially in very old patients who carry many risk factors for bleeding. We performed a large multicenter prospective observational study that enrolled very old patients to evaluate the quality of anticoagulation and the incidence of bleedings. Methods and Results— The study included 4093 patients ≥80 years of age who were naïve to VKA for thromboprophylaxis of atrial fibrillation or after venous thromboembolism. Patients' demographic and clinical data were collected, and the quality of anticoagulation and the incidence of bleeding were recorded. The follow-up was 9603 patient-years; median age at the beginning of follow-up was 84 years (range, 80 to 102 years). We recorded 179 major bleedings (rate, 1.87 per 100 patient-years), 26 fatal (rate, 0.27 per 100 patient-years). The rate of bleeding was higher in men compared with women (relative risk, 1.4; 95% confidence interval, 1.12 to 1.72; P =0.002) and among patients ≥85 years of age compared with younger patients (relative risk, 1.3; 95% confidence interval, 1.0 to 1.65; P =0.048). Time in therapeutic range was 62% (interquartile range, 49% to 75%). History of bleeding, active cancer, and history of falls were independently associated with bleeding risk in Cox regression analysis. Conclusion— In this large study on very old patients on VKA carefully monitored by anticoagulation clinics, the rate of bleedings was low, suggesting that age in itself should not be considered a contraindication to treatment. Adequate management of VKA therapy in specifically trained center allows very old and frail patients to benefit from VKA thromboprophylaxis.

For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (⩽10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients.

BACKGROUND: The optimal duration of anticoagulant treatment after venous thromboembolism (VTE) should be evaluated in relation to bleeding risk. This assessment is particularly difficult with elderly patients, because of their increased risk of both recurrences and hemorrhages. Bleeding risk stratification models have been proposed, but their predictive ability in very elderly patients is unknown. We aimed to assess six bleeding stratification models in this setting, by using information available in our dataset. PATIENTS AND METHODS: Patients aged >/= 80 years receiving vitamin K antagonists (VKAs) for the secondary prevention of VTE were eligible for this prospective cohort study. All patients were followed at Italian anticoagulation clinics for monitoring of VKA treatment. Risk factors for bleeding were collected, and major bleeding events and mortality were documented during follow-up. The association of bleeding events with the available risk factors was tested by means of Cox regression analysis; the c-statistic was used to quantify the predictive validity of the classification schemes. RESULTS: A total of 1078 patients (37.2% males; mean age, 84 years) were enrolled in the study, for a total observation period of 1981 patient-years. The rate of major bleeding was 2.4 per 100 patient-years (47 events; one was fatal). The mortality rate was 5.2 per 100 patient-years. None of the considered risk factors were significantly associated with bleeding events. The predictive validity of the risk stratification models was low, and the most accurate model was not specifically developed for VTE patients (HEMORR2 HAGES, c-statistic 0.60, 95% confidence interval 0.49-0.70). CONCLUSIONS: Bleeding risk stratification models appear to have little accuracy in very elderly VTE patients.