Objectives The aim of this study was to examine mortality and liver disease among patients exposed to dronedarone. Background There has been concern about the safety of dronedarone, especially for ...patients with heart failure and permanent atrial fibrillation (AF). There have also been suspicions about liver toxicity. Methods All 174,995 patients with a diagnosis of AF during 2010 to 2012 were identified in the Swedish Patient Register. Of these, 4,856 patients had received dronedarone according to the Swedish Drug Register, and 170,139 patients who had not were used as a control population. Mean follow-up was 1.6 years, with a minimal follow-up of 6 months. Results Patients prescribed dronedarone were younger (age 65.5 years vs. 75.7 years, p < 0.0001) and healthier than control patients. The annual mortality rate among patients who received dronedarone was 1.3% compared with 14.0% in the control population. There were no sudden cardiac deaths and no deaths related to liver failure among patients who received treatment with dronedarone. After propensity score matching and adjustment for cofactors, patients who received dronedarone had lower mortality than other AF patients (hazard ratio HR: 0.41; 95% confidence interval CI: 0.33 to 0.51). Dronedarone patients with heart failure had lower mortality than other heart failure patients (HR: 0.40; 95% CI: 0.30 to 0.53). They also had lower mortality than expected from the general population (standardized mortality ratio: 0.67; 95% CI: 0.55 to 0.78), which indicates the selection of low-risk patients. The risk of liver disease was not increased (HR: 0.57; 95% CI: 0.34 to 0.92). Conclusions Dronedarone, as prescribed to AF patients in Sweden, has not exposed patients to increased risks of death or liver disease.
To study the prevalence of unknown atrial fibrillation (AF) in a high-risk, 75/76-year-old, population using N-terminal B-type natriuretic peptide (NT-proBNP) and handheld electrocardiogram (ECG) ...recordings in a stepwise screening procedure.
The STROKESTOP II study is a population-based cohort study in which all 75/76-year-old in the Stockholm region (n = 28 712) were randomized 1:1 to be invited to an AF screening programme or to serve as the control group. Participants without known AF had NT-proBNP analysed and were stratified into low-risk (NT-proBNP <125 ng/L) and high-risk (NT-proBNP ≥125 ng/L) groups. The high-risk group was offered extended ECG-screening, whereas the low-risk group performed only one single-lead ECG recording. In total, 6868 individuals accepted the screening invitation of which 6315 (91.9%) did not have previously known AF. New AF was detected in 2.6% 95% confidence interval (CI) 2.2-3.0 of all participants without previous AF. In the high-risk group (n = 3766/6315, 59.6%), AF was diagnosed in 4.4% (95% CI 3.7-5.1) of the participants. Out of these, 18% had AF on their index-ECG. In the low-risk group, one participant was diagnosed with AF on index-ECG. The screening procedure resulted in an increase in known prevalence from 8.1% to 10.5% among participants. Oral anticoagulant treatment was initiated in 94.5% of the participants with newly diagnosed AF.
N-terminal B-type natriuretic peptide-stratified systematic screening for AF identified 4.4% of the high-risk participants with new AF. Oral anticoagulant treatment initiation was well accepted in the group diagnosed with new AF.
Background The long-term impact of new-onset postoperative atrial fibrillation (POAF) after coronary artery bypass grafting and the benefit of early-initiated oral anticoagulation (OAC) in patients ...with POAF are uncertain. Methods and Results All patients who underwent coronary artery bypass grafting without preoperative atrial fibrillation in Sweden from 2007 to 2015 were included in a population-based study using data from 4 national registries: SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies), National Patient Registry, Dispensed Drug Registry, and Cause of Death Registry. POAF was defined as any new-onset atrial fibrillation during the first 30 postoperative days. Cox regression models (adjusted for age, sex, comorbidity, and medication) were used to assess long-term outcome in patients with and without POAF, and potential associations between early-initiated OAC and outcome. In a cohort of 24 523 patients with coronary artery bypass grafting, POAF occurred in 7368 patients (30.0%), and 1770 (24.0%) of them were prescribed OAC within 30 days after surgery. During follow-up (median 4.5 years, range 0‒9 years), POAF was associated with increased risk of ischemic stroke (adjusted hazard ratio aHR 1.18 95% CI, 1.05‒1.32), any thromboembolism (ischemic stroke, transient ischemic attack, or peripheral arterial embolism) (aHR 1.16, 1.05‒1.28), heart failure hospitalization (aHR 1.35, 1.21‒1.51), and recurrent atrial fibrillation (aHR 4.16, 3.76‒4.60), but not with all-cause mortality (aHR 1.08, 0.98‒1.18). Early initiation of OAC was not associated with reduced risk of ischemic stroke or any thromboembolism but with increased risk for major bleeding (aHR 1.40, 1.08‒1.82). Conclusions POAF after coronary artery bypass grafting is associated with negative prognostic impact. The role of early OAC therapy remains unclear. Studies aiming at reducing the occurrence of POAF and its consequences are warranted.
Dysglycaemia is associated with overall cardiovascular disease even at prediabetes levels. The aim of this study was to explore the association between glucose levels and future risk of developing ...atrial fibrillation and heart failure, respectively.
In this prospective cohort study subjects from the Swedish AMORIS-cohort with fasting glucose from health examinations 1985-1996 without previous cardiovascular disease (N = 294,057) were followed to 31 December 2011 for incident atrial fibrillation or heart failure. Cox proportional hazard models with attained age as timescale and adjustments for sex, cholesterol, triglycerides, and socioeconomic status were used to estimate hazard ratios by glucose categorized groups (normal glucose 3.9-6.0 mmol/L, impaired fasting glucose; 6.1-6.9 mmol/L, undiagnosed diabetes ≥ 7.0 mmol/L, and diagnosed diabetes).
During a mean follow-up time of 19.1 years 28,233 individuals developed atrial fibrillation and 25,604 developed heart failure. The HR for atrial fibrillation was 1.19 (95% confidence interval 1.13-1.26) for impaired fasting glucose, 1.23 (1.15-1.32) for undiagnosed diabetes and 1.30 (1.21-1.41) for diagnosed diabetes. Corresponding figures for heart failure were; 1.40 (1.33-1.48), 2.11 (1.99-2.23), 2.22 (2.08-2.36) respectively. In a subset with BMI data (19%), these associations were attenuated and for atrial fibrillation only remained statistically significant among subjects with diagnosed diabetes (HR 1.25; 1.02-1.53).
Fasting glucose at prediabetes levels is associated with development of atrial fibrillation and heart failure. To some extent increased BMI may drive this association.
Background
It is unknown whether renal dysfunction conveys poor anticoagulation control in warfarin‐treated patients with atrial fibrillation and whether poor anticoagulation control associates with ...the risk of adverse outcomes in these patients.
Methods and Results
This was an observational study from the Stockholm CREatinine Measurements (SCREAM) cohort including all newly diagnosed atrial fibrillation patients initiating treatment with warfarin (n=7738) in Stockholm, Sweden, between 2006 and 2011. Estimated glomerular filtration rate (eGFR; mL/min per 1.73 m2) was calculated from serum creatinine. Time‐in‐therapeutic range (TTR) was assessed from international normalized ratio (INR) measurements up to warfarin cessation, adverse event, or end of follow‐up (2 years). Adverse events considered a composite of intracranial hemorrhage, ischemic stroke, myocardial infarction, or death. During median 254 days, TTR was 83%, based on median 21 INR measurements per patient. TTR was 70% among patients with eGFR <30, around 10% lower than in those with normal renal function. During observation, adverse events occurred in 4.0% of patients, and those with TTR ≤75% were at higher adverse event risk. This was independent of patient characteristics, comorbidities, number of INR tests, days exposed to warfarin, and, notably, independent of eGFR: adjusted odds ratio (OR) 1.84 (95% CI, 1.41–2.40) for TTR 75% to 60% and adjusted OR 2.09 (1.59–2.74) for TTR <60%. No interaction was observed between eGFR and TTR in association to adverse events (P=0.2).
Conclusion
Severe chronic kidney disease (eGFR <30) patients with atrial fibrillation have worse INR control while on warfarin. An optimal TTR (>75%) is associated with lower risk of adverse events, independently of underlying renal function.
The Swedish healthcare system aims to provide equal access to care to all residents yet evidence suggests that patients with low socioeconomic status are less likely to receive new drugs. ...Associations between sociodemographics and prescription of non-vitamin K antagonist oral anticoagulants (NOACs) as an alternative to warfarin in Sweden have not been investigated.
We conducted a cross-sectional study using linked national registers in Sweden. The study population included oral anticoagulant naïve patients aged ≥18 years with non-valvular atrial fibrillation (NVAF) who filled a first prescription for a NOAC or warfarin from 01 December 2011 to 31 December 2014. Multivariable logistic regression was used to identify factors associated with the choice of anticoagulant treatment; adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.
Among 68,056 patients with NVAF, 27.4% (N = 18,638) started treatment with a NOAC and 72.6% (N = 49,418) started on warfarin. Patients starting treatment with a NOAC were more likely to be highly educated (OR 1.37, 95% CI: 1.30-1.45), in the highest income quartile (OR 1.23, 95% CI: 1.16-1.31) and have a leading professional occupation (OR 1.41, 95% CI: 1.27-1.58). Patients residing in rural areas were half as likely to start treatment with a NOAC as those in urban areas (OR 0.48, 95% CI: 0.45-0.51).
Among Swedish patients with NVAF, those with high socioeconomic status and urban residence were more likely to start preventative treatment with a NOAC than warfarin. Future research should explore reasons for these inequalities in NOAC treatment.
Atrial fibrillation (AF) is the most prevalent clinical arrhythmia and a major risk factor for ischaemic stroke. Treatment with oral anticoagulants (OACs) reduces the risk of stroke by two thirds in ...AF patients with risk factors. Due to its often paroxysmal and asymptomatic presentation, AF is sometimes challenging to diagnose. So far, AF screening studies have applied opportunistic or systematic screening, most often using a single 12-lead electrocardiogram (ECG) recording or ambulatory ECG. We hypothesise that the biomarker N-terminal pro b-type natriuretic peptide (NT-proBNP) is a valuable adjunct in population based AF screening.
We are conducting a randomized population-based study on AF screening using ambulatory ECG recording where the decision to use prolonged intermittent ECG recording is directed by NT-proBNP levels, the STROKESTOP II trial. The entire population of inhabitants 75 or 76 years of age (n = 28 712) in the capital region of Sweden will be randomized 1:1 to intervention or control group. In the intervention group NT-proBNP will be analysed in all without previously known AF. Those with NT-proBNP ≤ 125 pg/L will make a single one lead ECG recording, participants with NTproBNP ≥ 125 np/L will be instructed to record ECG for 30 s at least twice daily for 2 weeks with a handheld ambulatory ECG recorder. Participants with newly diagnosed or undertreated AF will be referred to a cardiologist and offered OAC treatment. Primary endpoint is incidence of stroke or systemic embolus, during a 5 year follow-up period in the control group vs the group invited to screening.
The aim of the study was to assess and compare the safety of antiarrhythmic drugs (AADs) in an unselected real-world population of patients with atrial fibrillation (AF).
This is a study of all ...patients with diagnosed AF in the Swedish Patient register who filled a prescription for sotalol, amiodarone, dronedarone, flecainide or disopyramide during 2010 to 2015. The main end point consisted of arrhythmic death, successful resuscitation, new diagnosis of sustained ventricular tachycardia, ventricular fibrillation or implantation of ICD. All-cause mortality was a secondary end point. Minimum follow up was 1 year. Falsification end points were used to assess hidden confounding.
44,995 AF patients on AAD and 267,518 AF patients without AAD were studied during a total time at risk of over 1.1 million years. Compared to sotalol, the risk for the main end point was decreased with dronedarone (hazard ratio HR 0.58, 95% confidence interval CI 0.37–0.90), similar with flecainide (HR 0.95, 0.69–1.32) and disopyramide (HR 1.30, CI 0.83–2.05). All-cause mortality was lower with dronedarone (HR 0.44, CI 0.34–0.57) and flecainide (HR 0.55, CI 0.44–0.68) than with sotalol. Hidden confounding prevented reliable assessment of amiodarone.
Dronedarone was the only anti-arrhythmic drug with significantly lower risk for arrhythmic death, sustained ventricular arrhythmia or ICD implantation than sotalol among patients with atrial fibrillation. Both dronedarone and flecainide were associated with lower all-cause mortality than sotalol.
Background
The 2020 European Society of Cardiology atrial fibrillation guidelines recommend opportunistic screening for atrial fibrillation by pulse taking or ECG rhythm strip in those aged over 65 ...years.
Hypothesis
We aimed to compare the diagnostic accuracy of pulse palpation to ECG rhythm strip when screening for atrial fibrillation. A secondary aim was to investigate whether participants with palpitations were more likely to be diagnosed with new atrial fibrillation.
Methods
The study population were 75/76 year old individuals that participated in the STROKESTOP II study, a Swedish screening study for atrial fibrillation. Pulse palpation of the radial pulse for 30 sec was performed by healthcare professionals and recorded as regular or irregular. Thereafter a 30‐sec single‐lead ECG was registered. Patients were asked also if they had a history of palpitations.
Results
Of the 6159 participants included in the study, 461 (7.5%) had irregular pulse. Twenty‐two (4.8%) of those with irregular pulse were diagnosed with atrial fibrillation on single‐lead ECG rhythm strip. Among those with regular pulse, 6 (0.1%) cases of new atrial fibrillation were found. The sensitivity of the pulse palpation test was 78.6% and positive predictive value 4.8%. The proportion of newly diagnosed atrial fibrillation was not different between those with and without history of palpitations.
Conclusion
Pulse palpation was inferior to single‐lead ECG when screening for atrial fibrillation. We therefore advocate the use of single‐lead ECG rather than pulse palpation when screening for atrial fibrillation. Palpitations did not predict atrial fibrillation.
Abstract
Aims
The association between atrial fibrillation (AF) and dementia is well documented, but it is not clear if oral anticoagulant treatment offers protection. The aim of the study is ...therefore to compare the incidence of new dementia in patients with AF with and without oral anticoagulants, and to explore if there is a difference between novel anticoagulants and warfarin in this respect.
Methods and results
Retrospective registry study of all patients with hospital diagnosis of AF and no previous diagnosis of dementia in Sweden between 2006 and 2014. Propensity score matching, falsification endpoints, and analyses according to intention to treat as well as on-treatment principles were used. The study included 444 106 patients and over 1.5 million years at risk. Patients on anticoagulant treatment at baseline was associated with 29% lower risk of dementia than patients without anticoagulant treatment hazard ratio (HR) 0.71, 95% confidence intervals (95% CI) 0.68–0.74 and 48% lower risk analysed on treatment (HR 0.52, 95% CI 0.50–055). Direct comparison between new oral anticoagulants and warfarin showed no difference (HR 0.97, 95% CI 0.67–1.40).
Conclusion
The risk of dementia is higher without oral anticoagulant treatment in patients with AF. This suggests that early initiation of anticoagulant treatment in patients with AF could be of value in order to preserve cognitive function.
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