BACKGROUND It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82). CONCLUSIONS Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized.

Background The aim of this study is to examine the relationship between time in therapeutic range (TTR) and clinical outcomes in heart failure (HF) patients in sinus rhythm (SR) treated with warfarin. Methods and Results We used data from the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction Trial (WARCEF) to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death); with death alone; ischemic stroke alone; major hemorrhage alone; and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin patients, with TTR being treated as a time-dependent covariate. 2,217 patients were included in the analyses, among whom 1,067 were randomized to warfarin and 1,150 were randomized to aspirin. The median (IQR) follow-up duration was 3.6 (2.0–5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted p<0.001), death alone (adjusted p=0.001), and improved net clinical benefit (adjusted p<0.001). A similar trend was observed for the other two outcomes but significance was not reached (adjusted p=0.082 for ischemic stroke, adjusted p=0.109 for major hemorrhage). Conclusions In HF patients in SR, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.

Background: recent studies indicate that measurement of natriuretic peptides may be a valuable tool to improve the quality of the diagnosis of heart failure in general practice. Aim: the aim of the present study was to examine the relationship between the plasma level of the natriuretic peptide N-terminal proANP and symptoms and signs of heart failure in patients from general practice in the Oslo area. Methods and Results: we undertook a survey of 499 patients consecutively enrolled from the practice of 27 practitioners. One hundred and twenty-nine patients were classified as having possible or some degree of heart failure. The plasma concentration of N-terminal proANP increased with severity of heart failure as judged from clinical examination. In multivariate analysis age, history of heart disease, plasma creatinine, use of beta-blockers and digitalis, oedemas and atrial fibrillation were the main determinants of plasma N-terminal proANP. Conclusion: while there was an overall increase in N-terminal proANP values with increasing symptoms and degree of heart failure, no single finding was closely related to N-terminal proANP. Treatment effects and diagnostic errors may both influence the relationship between N-terminal proANP and clinical findings. The current study has demonstrated the feasibility of using N-terminal proANP by general practitioners for the potentially improved diagnosis of heart failure. Further research is required to determine the precise role of this assay in clinical practice. ᮊ

Background To assess baseline characteristics, drug utilisation and healthcare use for oral anticoagulants (OACs) following the introduction of non-vitamin K antagonist oral anticoagulants among patients with atrial fibrillation in primary care in Norway. Methods In this retrospective longitudinal cohort study, 92,936 patients with atrial fibrillation were identified from the Norwegian Primary Care Registry between 2010 and 2018. Linking to the Norwegian Prescription Database, we identified 64,112 patients (69.0%) treated with OACs and 28,824 (31%) who were untreated. Participants were followed until 15 May 2019, death, or loss to follow-up, whichever came first. For each OAC, predictors of initiation were assessed by modelling the probability of initiating the OAC using logistic regression, and predictors of the first switch after index date were assessed using multivariable Cox proportional hazards models. The numbers of primary care visits per quarter by index OAC were plotted and analysed with negative binomial regression analyses offset for the log of days at risk. Results Patients treated with OACs were older, had more comorbidities, and higher CHA2DS2-VASc scores than untreated patients. However, the mean CHA2DS2-VASc in the non-OAC group was 1.58 for men and 3.13 for women, suggesting an indication for OAC therapy. The percentage of patients with atrial fibrillation initiating OACs increased from 59% in 2010 to 79% in 2018. Non-vitamin K antagonist oral anticoagulant use increased throughout the study period to 95% of new OAC-treated patients in 2018, and switches from warfarin to non-vitamin K antagonist oral anticoagulants were common. The persistence of OAC treatment was > 60% after four years, with greatest persistence for apixaban. Patients treated with non-vitamin K antagonist oral anticoagulants had fewer primary care visits compared with those treated with warfarin (incidence rate ratio: 0.73, 95% confidence interval 0.71 to 0.75). Conclusion In this Norwegian primary care study, we found that the shift from warfarin to non-vitamin K antagonist oral anticoagulants was successful with 95% use in patients initiating OACs in 2018, and associated with fewer general practitioner visits. Persistence with OACs was high, particularly for apixaban. However, many patients eligible for treatment with OACs remained untreated.