Reasons for and consequences of vitamin K antagonist discontinuation in very elderly patients with non-valvular atrial fibrillation.

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 CHA2 DS2 -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 physician-perceived 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.

Vitamin K antagonists' use and fracture risk: results from a systematic review and meta-analysis.

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 ± 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 cross-sectional (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 = - 0.45; 95% CI: - 0.75, - 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.