Effects of Direct Oral Anticoagulants' Nonrecommended Dose in Atrial Fibrillation: A Meta-Analysis.

BACKGROUND: The efficacy and safety profiles of nonrecommended direct oral anticoagulant (DOAC) doses in patients with nonvalvular atrial fibrillation (NVAF) are still undefined. SUMMARY: We searched for randomized controlled trials and observational studies that compared nonrecommended versus recommended doses of DOACs, published up to December 2021. Primary study outcomes were ischemic stroke/transient ischemic attack/systemic embolism (IS/TIA/SE) and major bleeding (MB). All-cause mortality was a secondary outcome. We determined pooled odds ratios (ORs) between groups of patients with a random-effect model. Twenty-three studies with 175,801 patients were included. Nonrecommended doses were associated with a higher risk of IS/TIA/SE and all-cause mortality, but not of MB as compared to recommended doses of DOACs (OR 1.25 [95% CI: 1.14-1.38], OR 1.69 [95% CI: 1.31-2.18] and OR 1.10 [95% CI: 0.93-1.31], respectively). The nonrecommended low dose was associated with an increased risk of IS/TIA/SE and all-cause death (OR 1.21 [95% CI: 1.05-1.39] and OR 1.66 [95% CI: 1.18-2.35], respectively) but not of MB (OR 1.01 [95% CI: 0.83-1.22] as compared to recommended doses. Subgroup analysis of nonrecommended low doses of DOACs showed a nonsignificant increase in IS/TIA/SE in Asians (OR 1.17 [95% CI: 0.89-1.54] vs. non-Asian (OR 1.21 [95% CI: 1.07-1.36]). KEY MESSAGES: Compared with recommended doses, nonrecommended low doses of DOACs increase the risk of ischemic events without decreasing the risk of bleeding. For Asians, the efficacy of DOACs seemed preserved despite the nonrecommended low-dose prescription. Clinicians should carefully adhere to recommended DOAC prescription advice in managing NVAF patients.

Data on the use of oral anticoagulants in nonagenarians with atrial fibrillation.

The data presented in this article are related to the research article entitled "Patients aged 90 years or older with atrial fibrillation treated with oral anticoagulants: A multicentre observational study" [1]. This article unveils original data of a cohort of 546 patients aged 90 years or older with non-valvular atrial fibrillation treated with oral anticoagulants. Here, we describe the time course of ischemic stroke and systemic embolism and of major bleeding according to the presence of outcome predictors and report the causes of permanent discontinuation and of death. Furthermore, we report data on the incidence of ischemic stroke and systemic embolism, of major bleeding, of permanent discontinuation and of all-cause death comparing i) oral anticoagulant naïve users vs. long-term oral anticoagulant users, ii) patients on anticoagulant therapy for less than 2 years (new users) vs. patients on anticoagulant therapy for more than 2 years. The material of this data article provides a better understanding on the use of oral anticoagulants in this fragile population and facilitates further critical analysis. Moreover, it aims at highlighting the importance of increasing knowledge in patients aged 90 years or older. These patients are often excluded from or under-represented in clinical trials and cohort studies.

Patients aged 90 years or older with atrial fibrillation treated with oral anticoagulants: A multicentre observational study.

BACKGROUND: Patients aged 90 years or older are often excluded from or under-represented in clinical trials and cohort studies. The clinical benefit of anticoagulation in nonagenarians with atrial fibrillation (AF) remains undefined. OBJECTIVES: To assess the effectiveness and safety of oral anticoagulants in AF patients aged 90 years or older. METHODS: Non-valvular AF patients aged 90 years or older receiving direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) were included in this observational multicentre study. The primary outcome was the composite of ischaemic stroke/transient ischemic attack (TIA) and systemic embolism (SE). Major bleeding (MB), anticoagulant discontinuation and all-cause death were also assessed. Results are reported as sub-distribution hazard ratios (SHR) with 95% CI, taking death as competing risk. RESULTS: 546 patients were included (301 VKAs retrospective cohort and 245 DOACs prospective cohort; median follow-up 404 days). The rate of ischaemic stroke/TIA/SE was 2.4% patient-year and that of MB 5.5% patient-year. Previous ischaemic stroke/TIA (SHR 3.47; 95% CI 1.54-7.81) and vascular disease (SHR 2.89; 95% CI 1.27-6.60) were independent predictors of ischaemic stroke/TIA/SE. Previous bleeding (SHR 2.53; 95% CI 1.37-4.64) was an independent predictor of MB. The risk of ischaemic stroke/TIA/SE (SHR 0.78, 95% CI 0.30-2.04) or MB (SHR 1.43, 95% CI 0.77-2.65) was not significantly different with DOACs or VKAs. CONCLUSIONS: In AF nonagenarians receiving anticoagulant treatment, the rate of ischaemic stroke/TIA/SE is relatively low with the drawback of a not negligible rate of MB. DOACs seem a reasonable option for prevention of ischaemic stroke/TIA/SE in this setting.

Patients with cancer and atrial fibrillation treated with doacs: A prospective cohort study.

BACKGROUND: Limited data are available on the use of direct oral anticoagulants (DOACs) in patients with cancer and atrial fibrillation (AF). METHODS: Consecutive patients with non-valvular AF treated with DOACs were enrolled in a prospective cohort with the aim of evaluating thromboembolic (ischemic stroke or transient ischemic attack or systemic embolism) and major bleeding (MB) events according to presence and type of cancer. The risk of study outcomes over time was compared using Kaplan-Meier method and log-rank test or Cox proportional hazards regression. RESULTS: 2304 patients with non-valvular AF receiving DOACs were enrolled and 16 excluded: 2288 analysed of whom 289 (12.6%) had cancer. Gastrointestinal (21%), genitourinary (15%), prostate (15%), haematological (14%), breast (13%), and lung (8%) were the more frequent sites of cancer. After a mean follow-up of 451 days, thromboembolic events occurred in 2.1% and 0.8% patient-year of cancer and non-cancer patients (adjusted-HR 2.58, 95% CI 1.08-6.16, p = 0.033). The rate of MB was 6.6% and 3.0% patient-year in cancer and non-cancer patients (adjusted-HR 2.02, 95% CI 1.25-3.27, p = 0.004). The differences in bleeding were mainly accounted for by bleeding at gastrointestinal and genitourinary sites. No significant differences were found concerning the rates of non-cancer-related mortality, fatal bleeding or fatal thrombotic events. CONCLUSIONS: In this study, the higher bleeding risk found in cancer compared to non-cancer patients was mainly due to an excess of bleeding at gastrointestinal and at genitourinary sites. Larger studies on the optimal management of cancer patients with AF are needed.