Effectiveness and safety of self-managed oral anticoagulant therapy compared with direct oral anticoagulants in patients with atrial fibrillation

Abstract We compared the effectiveness and safety of direct oral anticoagulants (DOAC) vs patient self-managed warfarin therapy (PSM) in patients with atrial fibrillation. We linked prospectively registered data from university hospital clinics to nationwide Danish health registries. Primary effectiveness and safety outcomes were ischaemic stroke (incl. systemic embolism) and major bleeding. All-cause mortality and all-cause stroke were secondary outcomes. An inverse probability of treatment propensity-weighted approach was applied to adjust for potential confounding. The study cohorts included 534 patients treated with PSM and 2,671 patients treated with DOAC. Weighted rates of ischaemic stroke were 0.46 and 1.30 percent per year with PSM vs DOAC, hazard ratio (HR) 0.27 (95% confidence interval 0.11–0.68) with 2.5 years follow-up. Rates of major bleeding were 2.32 and 2.13 percent per year (HR 1.06 [0.69–1.63]). All-cause mortality was not statistically different (HR 0.67 [0.39–1.17]), whereas the incidence of all-cause stroke was significantly lower among patients treated with PSM with rates of 0.61 vs 1.45 percent per year (HR 0.36 [0.16–0.78]). In patients with atrial fibrillation, self-managed oral anticoagulant treatment was associated with a significantly lower risk of all-cause and ischaemic stroke compared to treatment with DOAC, whereas no significant differences were observed for major bleeding and mortality

Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation:propensity weighted nationwide cohort study

Objective To study the effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (novel oral anticoagulants, NOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin in anticoagulant naïve patients with atrial fibrillation. Design Observational nationwide cohort study. Setting Three Danish nationwide databases, August 2011 to October 2015. Participants 61 678 patients with non-valvular atrial fibrillation who were naïve to oral anticoagulants and had no previous indication for valvular atrial fibrillation or venous thromboembolism. The study population was distributed according to treatment type: warfarin (n=35 436, 57%), dabigatran 150 mg (n=12 701, 21%), rivaroxaban 20 mg (n=7192, 12%), and apixaban 5 mg (n=6349, 10%). Main outcome measures Effectiveness outcomes defined a priori were ischaemic stroke; a composite of ischaemic stroke or systemic embolism; death; and a composite of ischaemic stroke, systemic embolism, or death. Safety outcomes were any bleeding, intracranial bleeding, and major bleeding. Results When the analysis was restricted to ischaemic stroke, NOACs were not significantly different from warfarin. During one year follow-up, rivaroxaban was associated with lower annual rates of ischaemic stroke or systemic embolism (3.0% v 3.3%, respectively) compared with warfarin: hazard ratio 0.83 (95% confidence interval 0.69 to 0.99). The hazard ratios for dabigatran and apixaban (2.8% and 4.9% annually, respectively) were non-significant compared with warfarin. The annual risk of death was significantly lower with apixaban (5.2%) and dabigatran (2.7%) (0.65, 0.56 to 0.75 and 0.63, 0.48 to 0.82, respectively) compared with warfarin (8.5%), but not with rivaroxaban (7.7%). For the combined endpoint of any bleeding, annual rates for apixaban (3.3%) and dabigatran (2.4%) were significantly lower than for warfarin (5.0%) (0.62, 0.51 to 0.74). Warfarin and rivaroxaban had comparable annual bleeding rates (5.3%). Conclusion All NOACs seem to be safe and effective alternatives to warfarin in a routine care setting. No significant difference was found between NOACs and warfarin for ischaemic stroke. The risks of death, any bleeding, or major bleeding were significantly lower for apixaban and dabigatran compared with warfarin

Similarities and differences in systemic risk factors for retinal artery occlusion and stroke:A nationwide case-control study

BackgroundRetinal artery occlusion (RAO) has been considered a stroke equivalent. This study compares risk factor profiles for thromboembolism among patients with RAO and stroke, respectively.MethodsThis case-control study is based on 5683 RAO patients entered in the Danish National Patient Register between 1st of January 2000 and 31st of December 2018. Cases were matched on sex, year of birth, and age at event with 28,415 stroke patients. The Danish nationwide registries were used to collect information about age, sex, previous diagnoses, and drug prescriptions. Adjusted conditional logistic regression models were used to investigate the association between hypothesised risk factors and the patient outcome.ResultsFor atrial fibrillation, a substantially stronger association to stroke was found, with an odds ratio (OR) of 0.52 (95% CI: 0.47-0.58) when comparing RAO patients with stroke patients. RAO was stronger associated with arterial hypertension, peripheral artery disease, retinal vein occlusion, cataract, and glaucoma with OR's ranging from 1.21-11.70. The identified effect measures reached equivalence or was close to equivalence for diabetes, heart failure, ischemic heart disease, and renal disease.ConclusionThe differences in risk factor profiles between RAO and stroke suggests differences in the pathophysiology of the two diseases. These variations in pathophysiologies between the two diseases may indicate that different interventions are needed to ensure the optimal long-term prognosis for the patients

Cost Effectiveness of Patient Self‑Managed Warfarin Compared with Direct Oral Anticoagulants in Atrial Fibrillation: An Economic Evaluation in a Danish Healthcare Sector Setting

BACKGROUND: Patient self-managed anticoagulant treatment with warfarin (PSM) has been proposed as an alternative to direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF); however, direct evidence on the cost effectiveness of PSM compared with DOACs is lacking. We aimed to evaluate the cost effectiveness of PSM versus DOACs for NVAF patients in the Danish healthcare setting using a model-based cost-utility analysis. METHODS: A cost-utility analysis was performed using a decision-analytic model including two treatment alternatives: continuous PSM and DOACs. The analysis was performed from an extended Danish healthcare sector perspective, including patient-paid costs of medication related to the anticoagulant treatment, with a lifetime horizon. Inputs for the model comprised of probabilities of events, costs in Danish estimates, when possible, and effect in utilities. The probabilities of events are primarily based on real-life data from a direct comparison of PSM and DOACs. The results are presented as the incremental cost-effectiveness ratio (ICER) with an assumed cost-effectiveness threshold of £20,000/quality-adjusted life-year (QALY). Both deterministic and probabilistic sensitivity analyses were performed to investigate the robustness of the results. RESULTS: The base-analysis showed that PSM was dominant, with a decreased cost of £8495 and an increased QALY accumulation of 0.23 per patient (ICER = −£36,935/QALY). All deterministic sensitivity analyses indicated that PSM was dominant or at least cost effective. The probabilistic sensitivity analysis showed that 95% of the iterations were cost effective. CONCLUSIONS: The present study found that PSM is dominant (i.e., both more effective and cost saving) compared with DOACs, adding to the scarce evidence of the comparative cost effectiveness of PSM and DOACs in NVAF. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41669-022-00337-3

Assigning Diagnosis Codes Using Medication History

Diagnosis assignment is the process of assigning disease codes to patients. Automatic diagnosis assignment has the potential to validate code assignments, correct erroneous codes, and register completion. Previous methods build on text-based techniques utilizing medical notes but are inapplicable in the absence of these notes. We propose using patients' medication data to assign diagnosis codes. We present a proof-of-concept study using medical data from an American dataset (MIMIC-III) and Danish nationwide registers to train a machine-learning-based model that predicts an extensive collection of diagnosis codes for multiple levels of aggregation over a disease hierarchy. We further suggest a specialized loss function designed to utilize the innate hierarchical nature of the disease hierarchy. We evaluate the proposed method on a subset of 567 disease codes. Moreover, we investigate the technique's generalizability and transferability by (1) training and testing models on the same subsets of disease codes over the two medical datasets and (2) training models on the American dataset while evaluating them on the Danish dataset, respectively. Results demonstrate the proposed method can correctly assign diagnosis codes on multiple levels of aggregation from the disease hierarchy over the American dataset with recall 70.0% and precision 69.48% for top-10 assigned codes; thereby being comparable to text-based techniques. Furthermore, the specialized loss function performs consistently better than the non-hierarchical state-of-the-art version. Moreover, results suggest the proposed method is language and dataset-agnostic, with initial indications of transferability over subsets of disease codes