DOACs for Older adults with Atrial Fibrillation and Falls: Results from the prospective single-centre DOAFF study.

INTRODUCTION: Falls are one of the most fearsome events in anticoagulated older adults. The evidence concerning safety of direct oral anticoagulants (DOACs) in falling elderly patients with atrial fibrillation (AF) is still limited. METHODS: We prospectively enrolled consecutive anticoagulant-naïve patients aged 65 years and older, starting anticoagulation with DOACs for AF. The study cohort was stratified in fallers vs. non-fallers, according to the occurrence of at least one fall during the 2-year follow-up and bleeding outcomes were evaluated. RESULTS: We enrolled 524 consecutive patients. Mean age was 80.8 years and they were mostly women (54.0%). Among the study cohort, 148 patients (28.2%) presented at least one fall episode during the study period. After the adjustment for potential confounders, no difference was found between fallers and non-fallers for all the study outcomes: major bleeding [HR: 1.04 (95%CI: 0.58-1.85)], intracranial haemorrhage [HR: 1.63 (95%CI: 0.69-3.80)], clinically relevant non-major bleeding [HR: 1.21 (95%CI: 0.83-1.76)], and all-cause death [HR: 1.51 (95%CI: 0.85-2.69)]. The presence of a prior cerebrovascular event [HR: 2.27 (95%CI: 1.12-4.62); p-value: 0.02] and polypharmacy [HR: 1.60 (95%CI: 1.08-2.39); p-value: 0.02] were the main drivers for major and clinically relevant non-major bleedings, respectively. CONCLUSIONS: Falls in an anticoagulant-naïve population aged 65 years and over starting a DOAC for AF do not increase the bleeding risk. Thus, the presence of falls should not discourage clinicians from prescribing DOACs also in this subset of patients.

Efficacy and safety of direct oral anticoagulants in older adults with atrial fibrillation: a prospective single-centre cohort study.

INTRODUCTION: Direct oral anticoagulants (DOACs) are underused in the elderly, regardless the evidence in their favour in this population. METHODS: We prospectively enrolled anticoagulant-naïve patients aged ≥ 75 years who started treatment with DOACs for atrial fibrillation (AF) and stratified them in older adults (aged 75-84 years) and extremely older adults (≥ 85 years). Thrombotic and hemorrhagic events were evaluated for 12 months follow-up. RESULTS: We enrolled 518 consecutive patients. They were mostly aged 75-84 years (299 patients; 57.7%) vs. ≥ 85 years (219 patients; 42.3%). Extremely older adults showed higher incidence of all the endpoints (systemic cardioembolism [HR 3.25 (95% CI 1.71-6.18)], major bleeding [HR 2.75 (95% CI 1.77-4.27)], and clinically relevant non-major bleeding [HR 2.13 (95% CI 1.17-3.92)]) vs. older adults during the first year after starting anticoagulation. In patients aged ≥ 85 years, no difference in the aforementioned endpoints was found between those receiving on-label vs. off-label DOACs. In the extremely older adults, chronic kidney disease, polypharmacy, use of antipsychotics, and DOAC discontinuation correlated with higher rates of thrombotic events, whereas a history of bleeding, Charlson Index ≥ 6, use of reduced DOAC dose, absence of a caregiver, use of non-steroidal anti-inflammatory drugs (NSAIDs), and HAS-BLED score ≥ 3 were associated with major bleedings. CONCLUSIONS: Naïve patients aged ≥ 85 who started a DOAC for AF are at higher risk of thrombotic and bleeding events compared to those aged 75-84 years in the first year of therapy. History of bleeding, HAS-BLED score ≥ 3 and use of NSAIDs are associated with higher rates of major bleeding.

Association of body surface area with fat mass, free fat mass and total weight in healthy individuals, and implications for the dosage of cytotoxic drugs.

BACKGROUND & AIMS: In oncology, the dosage of anti-neoplastic drugs is generally adapted to the patient's body surface area (BSA). We investigated the potential differences between BSA and body weight (BW) in estimating the variability in body composition among individuals, especially older adults. MATERIALS AND METHODS: The study population included 322 community-dwelling individuals with different age and sex: 45 adult men (AM, age 18-65 years), 86 older men (OM, age >65 years), 54 adult women (AW, age 18-65 years), and 137 older women (OW, age >65 years). For each participant, we estimated the body composition with dual-energy X-ray absorptiometry, and we calculated the BSA using the DuBois and DuBois formula. The strength of relationships between fat free mass (FFM) and fat mass (FM) with BSA, BW, and BMI were expressed as correlation (r) and determination coefficients (R2). RESULTS: Most of the included sample was normal weight (45.7%) or overweight (41.9%). FFM demonstrated a stronger association with BSA than with BW or BMI in all age/sex groups, with r ranging from 0.831 to 0.924 (p < 0.001 for all) and R2 from 0.691 to 0.853. Conversely, BW and BMI were more strongly related to FM than BSA, especially in women. For such relationship, BW, in particular, showed r ranging from 0.793 to 0.924 (p < 0.001 for all). CONCLUSIONS: This study suggests that BSA may be more appropriately used to estimate FFM, compared with BW. Instead, alternative parameters should be considered to estimate FM in patients at risk for adverse effects of lipophilic drugs, especially in older age.

The Impact of Smoking on Bone Metabolism, Bone Mineral Density and Vertebral Fractures in Postmenopausal Women.

BACKGROUND: Smoking is recognized among the risk factors for osteoporosis, but only few studies have comprehensively explored its influence on bone metabolism and strength. We aimed to evaluate smoking effects on calcium-phosphate metabolism, bone mineral density (BMD) and fracture risk in postmenopausal women. METHODS: Our sample included 1067 postmenopausal women who arrived to our osteoporosis outpatient clinic. Anamnestic data, smoking habits (categorized as never, former, and current; and by smoking intensity and duration), biochemical parameters, lumbar/femoral BMD, and presence of vertebral fractures were recorded. In a subsample of 357 women, the changes in BMD after a 2-yr follow-up period were also assessed. RESULTS: Current smokers had shorter reproductive age, lower body mass index, and higher prevalence of heavy alcohol consumption than former/never smokers. They also had lower PTH values and weaker linear association between serum vitamin D and parathyroid hormone (current ß = -0.11[SE = 0.004]; former ß = -0.14[SE = 0.01]; never ß = -0.20[SE = 0.003]; p < 0.01 for all). Baseline BMD did not reflect differences based on smoking habits, duration or intensity. However, after 2 years, only current smokers significantly worsened in femural BMD. After adjustment for confounders, the chance of having sustained vertebral fractures at the first evaluation increased by 74% (95% confidence interval:1.07-2.83) in current compared with never smokers, especially among heavy smokers. CONCLUSIONS: Smoking may negatively affect bone by inhibiting vitamin D-parathyroid hormone axis, reducing estrogen exposure, promoting risky health behaviors, and accelerating bone loss, especially at the femur. No significant differences were observed in these outcomes among former smokers, suggesting that quitting smoking has beneficial effects on bone health.