Physical activity and risk of bleeding in elderly patients taking anticoagulants.

Although the possibility of bleeding during anticoagulant treatment may limit patients from taking part in physical activity, the association between physical activity and anticoagulation-related bleeding is uncertain. To determine whether physical activity is associated with bleeding in elderly patients taking anticoagulants. In a prospective multicenter cohort study of 988 patients aged ≥ 65 years receiving anticoagulants for venous thromboembolism, we assessed patients' self-reported physical activity level. The primary outcome was the time to a first major bleeding, defined as fatal bleeding, symptomatic bleeding in a critical site, or bleeding causing a fall in hemoglobin or leading to transfusions. The secondary outcome was the time to a first clinically relevant non-major bleeding. We examined the association between physical activity level and time to a first bleeding by using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. During a mean follow-up of 22 months, patients with a low, moderate, and high physical activity level had an incidence of major bleeding of 11.6, 6.3, and 3.1 events per 100 patient-years and an incidence of clinically relevant non-major bleeding of 14.0, 10.3, and 7.7 events per 100 patient-years, respectively. A high physical activity level was significantly associated with a lower risk of major bleeding (adjusted sub-hazard ratio 0.40, 95% confidence interval 0.22-0.72). There was no association between physical activity and non-major bleeding. A high level of physical activity is associated with a decreased risk of major bleeding in elderly patients receiving anticoagulant therapy.

Frey PM ，Méan M ，Limacher A ，Jaeger K ，Beer HJ ，Frauchiger B ，Aschwanden M ，Rodondi N ，Righini M ，Egloff M ，Osterwalder J ，Kucher N ，Angelillo-Scherrer A ，Husmann M ，Banyai M ，Matter CM ，Aujesky D ... -  《-》

A high Gas6 level in plasma predicts venous thromboembolism recurrence, major bleeding and mortality in the elderly: a prospective multicenter cohort study.

Essentials Predictive ability of pro-hemostatic Gas6 for recurrent venous thromboembolism (VTE) is unknown. We measured Gas6 levels in 864 patients with VTE over 3 years. High Gas6 (> 157%) at diagnosis is associated with VTE recurrence, major bleeding and mortality. Gas6 plasma levels measured 12 months after the index VTE are discriminatory for VTE recurrence. SUMMARY: Background Growth arrest-specific gene 6 (Gas6) is a prohemostatic protein with an unknown predictive ability for recurrent venous thromboembolism (VTE). In the elderly, VTE results in higher mortality but does not have a higher rate of recurrence than in younger patients. Consequently, anticoagulation management in the elderly is challenging. Objective To prospectively investigate the performance of Gas6 in predicting VTE recurrence, major bleeding and mortality in the elderly. Methods Consecutive patients aged ≥ 65 years with acute VTE were followed for a period of 3 years. Primary outcomes were symptomatic VTE recurrence, major bleeding, and mortality. Plasma Gas6 was measured with ELISA. Results Gas6 levels were measured in 864 patients at the time of the index VTE (T1) and, in 70% of them, also 12 months later (T2). The Gas6 level at T1 was discriminatory for VTE recurrence (C-statistic, 0.56; 95% confidence interval [CI] 0.51-0.62), major bleeding (0.60, 95% CI 0.55-0.65) and mortality (0.69, 95% CI 0.65-0.73) up to 36 months. VTE recurrence up to 24 months after T2 was discriminated by the Gas6 level at T2 (0.62, 95% CI 0.54-0.71). High Gas6 levels (> 157%) and continuous Gas6 levels at T1 were associated with VTE recurrence up to 6 months and 12 months, respectively. Conclusions In elderly patients, a high Gas6 level is associated with higher risks of VTE recurrence, major bleeding, and death. These findings support further studies to assess the performance of Gas6 in adjusting the length of anticoagulation.

Schnegg-Kaufmann A ，Calzavarini S ，Limacher A ，Mean M ，Righini M ，Staub D ，Beer JH ，Frauchiger B ，Osterwalder J ，Kucher N ，Matter CM ，Husmann M ，Banyai M ，Aschwanden M ，Mazzolai L ，Hugli O ，Nagler M ，Daskalakis M ，Rodondi N ，Aujesky D ，Angelillo-Scherrer A ... -  《-》

Polypharmacy is associated with an increased risk of bleeding in elderly patients with venous thromboembolism.

Leiss W ，Méan M ，Limacher A ，Righini M ，Jaeger K ，Beer HJ ，Osterwalder J ，Frauchiger B ，Matter CM ，Kucher N ，Angelillo-Scherrer A ，Cornuz J ，Banyai M ，Lämmle B ，Husmann M ，Egloff M ，Aschwanden M ，Rodondi N ，Aujesky D ... -  《-》

Risk of falls and bleeding in elderly patients with acute venous thromboembolism.

Whether or not a high risk of falls increases the risk of bleeding in patients receiving anticoagulants remains a matter of debate. We conducted a prospective cohort study involving 991 patients ≥ 65 years of age who received anticoagulants for acute venous thromboembolism (VTE) at nine Swiss hospitals between September 2009 and September 2012. The study outcomes were as follows: the time to a first major episode of bleeding; and clinically relevant nonmajor bleeding. We determined the associations between the risk of falls and the time to a first episode of bleeding using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. Four hundred fifty-eight of 991 patients (46%) were at high risk of falls. The mean duration of follow-up was 16.7 months. Patients at high risk of falls had a higher incidence of major bleeding (9.6 vs. 6.6 events/100 patient-years; P = 0.05) and a significantly higher incidence of clinically relevant nonmajor bleeding (16.7 vs. 8.3 events/100 patient-years; P < 0.001) than patients at low risk of falls. After adjustment, a high risk of falls was associated with clinically relevant nonmajor bleeding [subhazard ratio (SHR) = 1.74, 95% confidence interval (CI) = 1.23-2.46], but not with major bleeding (SHR = 1.24, 95% CI = 0.83-1.86). In elderly patients who receive anticoagulants because of VTE, a high risk of falls is significantly associated with clinically relevant nonmajor bleeding, but not with major bleeding. Whether or not a high risk of falls is a reason against providing anticoagulation beyond 3 months should be based on patient preferences and the risk of VTE recurrence.

Kämpfen P ，Méan M ，Limacher A ，Righini M ，Jaeger K ，Beer HJ ，Osterwalder J ，Frauchiger B ，Matter CM ，Kucher N ，Cornuz J ，Banyai M ，Egloff M ，Aschwanden M ，Bounameaux H ，Rodondi N ，Aujesky D ... -  《-》

Clinically relevant bleeding in cancer patients treated for venous thromboembolism from the CATCH study.

Essentials Cancer patients receiving anticoagulants for venous thromboembolism have an elevated bleeding risk. This secondary analysis of CATCH assessed characteristics of clinically relevant bleeding (CRB). CRB occurs in 15% of cancer patients with thrombosis using therapeutic doses of anticoagulation. After multivariate analysis, risk factors for CRB were age >75 years and intracranial malignancy. Background Cancer patients with acute venous thromboembolism (VTE) receiving anticoagulant treatment have an increased bleeding risk. Objectives We performed a prespecified secondary analysis of the randomized, open-label, Phase III CATCH trial (NCT01130025) to assess the rate and sites of and the risk factors for clinically relevant bleeding (CRB). Patients/Methods Patients with active cancer and acute, symptomatic VTE received either tinzaparin 175 IU kg-1 once daily or warfarin (target International Normalized Ratio [INR] of 2.0-3.0) for 6 months. Fisher's exact test was used to screen prespecified clinical risk factors; those identified as being significantly associated with an increased risk of CRB then underwent competing risk regression analysis of time to first CRB. Results Among 900 randomized patients, 138 (15.3%) had 180 CRB events. CRB occurred in 60 patients (81 events) in the tinzaparin group and in 78 patients (99 events) in the warfarin group (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.45-0.89). Common bleeding sites were gastrointestinal (36.7%; n = 66), genitourinary (22.8%; n = 41), and nasal (10.0%; n = 18). In multivariate analysis, the risk of CRB increased with age > 75 years (HR 1.83, 95% CI 1.14-2.94) and intracranial malignancy (HR 1.97, 95% CI 1.07-3.62). In the warfarin group, 40.4% of CRB events occurred in patients with with an INR of < 3.0. A lower time in therapeutic range was associated with a higher risk of CRB. Conclusions CRB is a frequent complication in cancer patients with VTE during anticoagulant treatment, and is associated with age > 75 years and intracranial malignancy.

Kamphuisen PW ，Lee AYY ，Meyer G ，Bauersachs R ，Janas MS ，Jarner MF ，Khorana AA ，CATCH Investigators ... -  《-》