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It is currently unknown whether thrombin generation is associated with venous thromboembolism (VTE) recurrence, major bleeding, or mortality in the elderly. Therefore, our aim was to prospectively study the association between thrombin generation and VTE recurrence, major bleeding, and mortality in elderly patients with acute VTE. Consecutive patients aged ≥65 years with acute VTE were followed for 2 years, starting from 1 year after the index VTE. Primary outcomes were VTE recurrence, major bleeding, and mortality. Thrombin generation was assessed in 551 patients 1 year after the index VTE. At this time, 59% of the patients were still anticoagulated. Thrombin generation was discriminatory for VTE recurrence, but not for major bleeding and mortality in non-anticoagulated patients. Moreover, peak ratio (adjusted subhazard ratio 4.09, 95% CI, 1.12–14.92) and normalized peak ratio (adjusted subhazard ratio 2.18, 95% CI, 1.28–3.73) in the presence/absence of thrombomodulin were associated with VTE recurrence, but not with major bleeding and mortality after adjustment for potential confounding factors. In elderly patients, thrombin generation was associated with VTE recurrence, but not with major bleeding and/or mortality. Therefore, our study suggests the potential usefulness of thrombin generation measurement after anticoagulation completion for VTE to help identify among elderly patients those at higher risk of VTE recurrence. [ABSTRACT FROM AUTHOR]

Whether anticoagulation management practices are associated with improved outcomes in elderly patients with acute venous thromboembolism (VTE) is uncertain. Thus, we aimed to examine whether practices recommended by the American College of Chest Physicians guidelines are associated with outcomes in elderly patients with VTE. We studied 991 patients aged ≥65 years with acute VTE in a Swiss prospective multicenter cohort study and assessed the adherence to four management practices: parenteral anticoagulation ≥5 days, INR ≥2.0 for ≥24 hours before stopping parenteral anticoagulation, early start with vitamin K antagonists (VKA) ≤24 hours of VTE diagnosis, and the use of low-molecular-weight heparin (LMWH) or fondaparinux. The outcomes were all-cause mortality, VTE recurrence, and major bleeding at 6 months, and the length of hospital stay (LOS). We used Cox regression and lognormal survival models, adjusting for patient characteristics. Overall, 9% of patients died, 3% had VTE recurrence, and 7% major bleeding. Early start with VKA was associated with a lower risk of major bleeding (adjusted hazard ratio 0.37, 95% CI 0.20–0.71). Early start with VKA (adjusted time ratio [TR] 0.77, 95% CI 0.69–0.86) and use of LMWH/fondaparinux (adjusted TR 0.87, 95% CI 0.78–0.97) were associated with a shorter LOS. An INR ≥2.0 for ≥24 hours before stopping parenteral anticoagulants was associated with a longer LOS (adjusted TR 1.2, 95% CI 1.08–1.33). In elderly patients with VTE, the adherence to recommended anticoagulation management practices showed mixed results. In conclusion, only early start with VKA and use of parenteral LMWH/fondaparinux were associated with better outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Polypharmacy, defined as the concomitant use of multiple medications, is very common in the elderly and may trigger drug-drug interactions and increase the risk of falls in patients receiving vitamin K antagonists. OBJECTIVE: To examine whether polypharmacy increases the risk of bleeding in elderly patients who receive vitamin K antagonists for acute venous thromboembolism (VTE). DESIGN: We used a prospective cohort study. PARTICIPANTS: In a multicenter Swiss cohort, we studied 830 patients aged ≥ 65 years with VTE. MAIN MEASURES: We defined polypharmacy as the prescription of more than four different drugs. We assessed the association between polypharmacy and the time to a first major and clinically relevant non-major bleeding, accounting for the competing risk of death. We adjusted for known bleeding risk factors (age, gender, pulmonary embolism, active cancer, arterial hypertension, cardiac disease, cerebrovascular disease, chronic liver and renal disease, diabetes mellitus, history of major bleeding, recent surgery, anemia, thrombocytopenia) and periods of vitamin K antagonist treatment as a time-varying covariate. KEY RESULTS: Overall, 413 (49.8 %) patients had polypharmacy. The mean follow-up duration was 17.8 months. Patients with polypharmacy had a significantly higher incidence of major (9.0 vs. 4.1 events/100 patient-years; incidence rate ratio [IRR] 2.18, 95 % confidence interval [CI] 1.32-3.68) and clinically relevant non-major bleeding (14.8 vs. 8.0 events/100 patient-years; IRR 1.85, 95 % CI 1.27-2.71) than patients without polypharmacy. After adjustment, polypharmacy was significantly associated with major (sub-hazard ratio [SHR] 1.83, 95 % CI 1.03-3.25) and clinically relevant non-major bleeding (SHR 1.60, 95 % CI 1.06-2.42). CONCLUSIONS: Polypharmacy is associated with an increased risk of both major and clinically relevant non-major bleeding in elderly patients receiving vitamin K antagonists for VTE. [ABSTRACT FROM AUTHOR]

Background: Combining high‐sensitivity cardiac Troponin T (hs‐cTnT), NT‐pro‐B‐type natriuretic peptide (NT‐proBNP) and high‐sensitivity C‐reactive protein (hs‐CRP) may improve risk stratification of patients with pulmonary embolism (PE) beyond the PESI risk score. Methods: In the prospective multicentre SWITCO65+ study, we analysed 214 patients ≥ 65 years with a new submassive PE. Biomarkers and clinical information for the PESI risk score were ascertained within 1 day after diagnosis. Associations of hs‐TnT, NT‐proBNP, hs‐CRP and the PESI risk score with the primary endpoint defined as 6‐month mortality were assessed. The discriminative power of the PESI risk score and its combination with hs‐cTnT, NT‐proBNP and hs‐CRP for 6‐month mortality was compared using integrated discrimination improvement (IDI) index and net reclassification improvement (NRI). Results: Compared with the lowest quartile, patients in the highest quartile had a higher risk of death during the first 6 months for hs‐cTnT (adjusted HR 10.22; 95% CI 1.79‐58.34; P = 0.009) and a trend for NT‐proBNP (adjusted HR 4.3; 95% CI 0.9‐20.41; P = 0.067) unlike hs‐CRP (adjusted HR 1.97; 95% CI 0.48‐8.05; P = 0.344). The PESI risk score (c‐statistic 0.77 (95% CI 0.69‐0.84) had the highest prognostic accuracy for 6‐month mortality, outperforming hs‐cTnT, NT‐proBNP and hs‐CRP (c‐statistics of 0.72, 0.72, and 0.54), respectively. Combining all three biomarkers had no clinically relevant impact on risk stratification when added to the PESI risk score (IDI = 0.067; 95% CI 0.012‐0.123; P = 0.018; NRI = 0.101 95% CI −0.099‐0.302; P = 0.321). Conclusions: In elderly patients with PE, 6‐month mortality can adequately be predicted by the PESI risk score alone. [ABSTRACT FROM AUTHOR]

Background: Long-term predictors and causes of death are understudied in elderly patients with acute venous thromboembolism.Methods: We prospectively followed up 991 patients aged ≥65 years with acute venous thromboembolism in a multicenter Swiss cohort study. The primary outcome was overall mortality. We explored the association between patient baseline characteristics and mortality, adjusting for other baseline variables and periods of anticoagulation as a time-varying covariate. Causes of death over time were adjudicated by a blinded, independent committee.Results: The median age was 75 years. During a median follow-up period of 30 months, 206 patients (21%) died. Independent predictors of overall mortality were age (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.05-1.65, per decade), active cancer (HR, 5.80; 95% CI, 4.22-7.97), systolic blood pressure <100 mm Hg (HR, 2.77; 95% CI, 1.56-4.92), diabetes mellitus (HR, 1.50; 95% CI, 1.02-2.22), low physical activity level (HR, 1.92; 95% CI, 1.38-2.66), polypharmacy (HR, 1.41; 95% CI, 1.01-1.96), anemia (HR, 1.48; 95% CI, 1.07-2.05), high-sensitivity C-reactive protein >40 mg/L (HR, 1.88; 95% CI, 1.36-2.60), ultra-sensitive troponin >14 pg/mL (HR, 1.54; 95% CI, 1.06-2.25), and D-dimer >3000 ng/mL (HR, 1.45; 95% CI, 1.04-2.01). Cancer (34%), pulmonary embolism (18%), infection (17%), and bleeding (6%) were the most common causes of death.Conclusions: Elderly patients with acute venous thromboembolism have a substantial long-term mortality, and several factors, including polypharmacy and a low physical activity level, are associated with long-term mortality. Cancer, pulmonary embolism, infections, and bleeding are the most common causes of death in the elderly with venous thromboembolism. [ABSTRACT FROM AUTHOR]

Background The evidence on the prognostic value of transthoracic echocardiography (TTE) in elderly, hemodynamically stable patients with Pulmonary Embolism (PE) is limited. Objectives To evaluate the prevalence of common echocardiographic signs of right ventricular (RV) dysfunction and their prognostic impact in hemodynamically stable patients aged ≥ 65 years with acute PE in a prospective multicenter cohort. Methods TTE was performed by cardiologists. We defined RV dysfunction as a RV/left ventricular ratio > 0.9 or RV hypokinesis (primary definition) or the presence of ≥ 1 or ≥ 2 of 6 predefined echocardiographic signs (secondary definitions). Outcomes were overall mortality and mortality/non-fatal recurrent venous thromboembolism (VTE) at 30 days, adjusting for the Pulmonary Embolism Severity Index risk score and highly sensitive troponin T values. Results Of 400 patients, 36% had RV dysfunction based on our primary definition, and 81% (≥ 1 sign) and 53% (≥ 2 signs) based on our secondary definitions, respectively. Using our primary definition, there was no association between RV dysfunction and mortality (adjusted HR 0.90, 95% CI 0.31–2.58) and mortality/non-fatal VTE (adjusted HR 1.09, 95% CI 0.40–2.98). Similarly, there was no statistically significant association between the presence of ≥ 1 or ≥ 2 echocardiographic signs (secondary definitions) and clinical outcomes. Conclusion The prevalence of echocardiographic RV dysfunction varied widely depending upon the definition used. There was no association between RV dysfunction and clinical outcomes. Thus, TTE may not be suitable as a stand-alone risk assessment tool in elderly patients with acute PE. Clinical trial registration http://clinicaltrials.gov . Identifier: NCT00973596 . [ABSTRACT FROM AUTHOR]