use and fracture risk: results from a systematic review and meta-analysis. J Thromb Haemost 2015; 13: 1665-75.Summary. Background: Although vitamin K antagonists (VKAs) lower serum values of bone deposition markers, the link with osteoporosis and fractures remains controversial. Objectives: To assess whether the use of VKAs is associated with an increased prevalence and/or incidence of osteoporosis, fractures, or lower bone mineral density (BMD) values. Methods: We conducted a systematic PubMed and EMBASE literature search until August 31, 2014, and a meta-analysis of cross-sectional and longitudinal studies investigating fractures and BMD, comparing patients treated with VKAs and healthy controls (HCs) or with patients with medical illness (medical controls, MCs). Standardized mean differences AE 95% and confidence intervals (CIs) were calculated for BMD, and risk ratios (RRs) were calculated for prevalent and incident fractures. Results: Of 4597 initial hits, 21 studies were eligible, including 79 663 individuals treated with VKAs vs. 597 348 controls. Compared with HCs, VKA-treated individuals showed significantly higher fracture risk in crosssectional (three studies; RR = 1.24; 95% CI: 1.12-1.39, P < 0.0001) and longitudinal studies (seven studies; RR = 1.09; 95% CI: 1.01-1.18, P = 0.03) and more incident hip fractures (four studies; RR = 1.17; 95% CI: 1.05-1.31, P = 0.003). Analyzing studies that matched VKA participants with HCs (four studies), both these findings in longitudinal studies became non-significant. Notably, the VKA and MC group had similar BMD values at all investigated sites. Compared with HCs, a single study showed significantly lower spine T-scores in the VKA-treated group (standardized mean difference = À 0.45; 95% CI: À 0.75, À 0.14, P = 0.004). Conclusion: VKAs neither increased prospectively-assessed fracture risk compared with MCs when matching eliminated confounding factors nor reduced BMD beyond effects of medical illness. Future studies, using careful matching and/or adequate MC groups, are needed to further clarify the short-and long-term effects of VKAs on bone health.

Essentials• Anticoagulation in the elderly is still a challenge and suspension of warfarin is common.• This is an observational study reporting reasons and consequences of warfarin suspension.• Vascular disease, age, time in therapeutic range, and bleedings are associated with suspension.• After suspension for bleeding or frailty, patients remain at high-risk of death or complications.Summary. Background: Anticoagulation in elderly patients with non-valvular atrial fibrillation (NVAF) is still a challenge, and discontinuation of warfarin is common. The aim of this study was to analyze the aspects related to warfarin discontinuation in a real-world population. Methods: This was an observational cohort study on very elderly NVAF patients naive to warfarin therapy (VENPAF). The included subjects were aged at least 80 years, and started using warfarin after a diagnosis of NVAF. Warfarin discontinuation was assessed, and the reason reported for discontinuation, the person who decided to stop treatment, subsequent antithrombotic therapy and mortality, ischemic and bleeding events were collected. Results: Over a period of 5 years, warfarin was discontinued in 148 of 798 patients.Despite similar CHA 2 DS 2 -VASc scores, the frequencies of thromboembolic and major bleeding events were significantly higher (P = 0.01 and P = 0.001, respectively) and the time in therapeutic range (TTR) was significantly lower (P < 0.001) in patients who discontinued warfarin. Independent risk factors for warfarin discontinuation were vascular disease (hazard ratio [HR] 2.5, P < 0.001), age ≥ 85 years (HR 1.4, P = 0.04), TTR < 60% (HR 1.8, P = 0.001), and bleeding events (HR 2.3, P < 0.001). The main reasons for warfarin discontinuation were physicianperceived frailty or low life-expectancy (45.9%), bleeding complications (19.6%), and sinus rhythm restoration (16.9%). Event and death rates were very high, especially in frail patients and in those with bleeding complications. Conclusions: Warfarin discontinuation is frequent in very elderly patients, and is associated with increased risks of death and adverse events. Identification of elderly patients who are at high risk of bleeding and the poor quality of anticoagulation during warfarin are still unsolved clinical problems.

Despite the recommendations in the guidelines, physicians still underuse warfarin in very elderly patients with non-valvular atrial fibrillation (NVAF). The risks of stroke and major bleeding both increase with age, but it is still not clear whether the beneficial effects of vitamin K antagonists (VKA) in preventing stroke outweigh the related bleeding risks in fragile, very elderly patients. The bleeding rates reported in real-world observational studies differ considerably. The aim of this study was to retrospectively assess the incidence of major bleeding in VKA-naïve patients over 80 years old with NVAF at a large anticoagulation clinic. Significant predictors of major bleeding were also investigated. Sixty-five major bleeding events (3.4 per 100 patient-years) and 25 thromboembolic events (1.3 per 100 patient-years) were recorded in a sample of 798 patients with a median follow-up of 2.2 years. Patients over 85 years old had significantly more major bleeding events than the 80- to 84-year olds (4.7 vs. 2.6 per 100 patient-years, p 0.014). Spontaneous bleeding was also significantly more common (3.0 vs. 1.3 per 100 patient-years, p 0.008) in the very elderly group. Age and diabetes were the only independent risk factor for bleeding on multivariate Cox analysis (Age HR 1.80, 95% CI 1.10-2.93; diabetes HR 1.76, 95% CI 1.00-3.09). These data show a sharp increase in major bleeding episodes among the very elderly with atrial fibrillation. Further studies are warranted with a view to identifying patients at risk.

Asymptomatic deep vein thrombosis (DVT) and pulmonary embolism are leading causes of morbidity following the hospitalization of elderly people. The diagnosis of DVT is supported by the D-dimer laboratory assay. The concentration of D-dimer increases in patients with DVT, but may be high in other conditions too (i.e. cancer, infections and inflammation). Old age coincides with a physiological increase in D-dimer values, and that is why D-dimer assay in the elderly is characteristically highly sensitive but scarcely specific. The aim of our study was to explore the reliability of different D-dimer cutoffs for the diagnosis of asymptomatic DVT in a population of bedridden hospitalized elderly patients. We studied 199 patients who were a mean 86.3 ± 6.7 years old. All participants underwent lower limb Doppler ultrasound (DUS) and D-dimer venous blood sampling on admission. In our cohort, the usual cutoff proved highly sensitive (100%), but its specificity was very poor (20.1%). To find a higher cutoff that could improve the method's specificity, we analyzed our data using a receiver operating characteristic curve analysis. The resulting D-dimer cutoff of 492 μg/l enabled us to retain the same sensitivity while improving the test's specificity to 39.1%, with a consequent improvement in its positive predictive value and accuracy. In addition to improving the method's reliability, this result may be helpful in clinical practice, in both medical wards and nursing homes. By adopting a cutoff of 492 μg/l, clinicians could significantly increase the proportion of older patients in whom DVT can be safely ruled out, reducing referrals for DUS and administration of heparin, with consequent clinical, practical and economic advantages.