scholarly journals Trends in excess mortality associated with atrial fibrillation over 45 years (Framingham Heart Study): community based cohort study

BMJ ◽  
2020 ◽  
pp. m2724
Author(s):  
Nicklas Vinter ◽  
Qiuxi Huang ◽  
Morten Fenger-Grøn ◽  
Lars Frost ◽  
Emelia J Benjamin ◽  
...  

AbstractObjectiveTo assess temporal trends in the association between newly diagnosed atrial fibrillation and death.DesignCommunity based cohort study.SettingFramingham Heart Study cohort, in 1972-85, 1986-2000, and 2001-15 (periods 1-3, respectively), in Framingham, MA, USA.ParticipantsParticipants with no atrial fibrillation, aged 45-95 in each time period, and identified with newly diagnosed atrial fibrillation (or atrial flutter) during each time period.Main outcome measuresThe main outcome was all cause mortality. Hazard ratios for the association between time varying atrial fibrillation and all cause mortality were calculated with adjustment for time varying confounding factors. The difference in restricted mean survival times, adjusted for confounders, between participants with atrial fibrillation and matched referents at 10 years after a diagnosis of atrial fibrillation was estimated. Meta-regression was used to test for linear trends in hazard ratios and restricted mean survival times over the different time periods.Results5671 participants were selected in time period 1, 6177 in period 2, and 6174 in period 3. Adjusted hazard ratios for all cause mortality between participants with and without atrial fibrillation were 1.9 (95% confidence interval 1.7 to 2.2) in time period 1, 1.4 (1.3 to 1.6) in period 2, and 1.7 (1.5 to 2.0) in period 3 (Ptrend=0.70). Ten years after diagnosis of atrial fibrillation, the adjusted difference in restricted mean survival times between participants with atrial fibrillation and matched referents decreased by 31%, from −2.9 years (95% confidence interval −3.2 to −2.5) in period 1, to −2.1 years (−2.4 to −1.8) in period 2, to −2.0 years (−2.3 to −1.7) in period 3 (Ptrend=0.03).ConclusionsNo evidence of a temporal trend in hazard ratios for the association between atrial fibrillation and all cause mortality was found. The mean number of life years lost to atrial fibrillation at 10 years had improved significantly, but a two year gap compared with individuals without atrial fibrillation still remained.

2021 ◽  
pp. 174749302110294
Author(s):  
Peter Nielsen ◽  
Mette Soegaard ◽  
Martin Jensen ◽  
Anne G Ording ◽  
Gregory Lip

Background and purpose: The effectiveness and safety of edoxaban 60 mg and 30 mg for stroke prevention compared with warfarin in patients with atrial fibrillation (AF) has not been well-described in a nationwide cohort of Caucasian patients treated in standard clinical practice. Methods: We used Danish nationwide registries to identify patients with AF during June 2016 and November 2018 who were treated with edoxaban or warfarin and computed rates per 100 person-years of thromboembolic, all-cause mortality, and bleeding events using an inverse probability of treatment weighting approach to account for baseline confounding. We used weighted pooled logistic regression to compute hazard ratios (HRs) with 95% confidence intervals (CIs) comparing events between edoxaban 60 mg and warfarin users; edoxaban 30 mg was not included in formal comparisons. Results: We identified 6451 AF patients, mean age was 72 years and 40% were females. A total of 1772 patients were treated with edoxaban 60 mg, 537 with edoxaban 30 mg, and 4142 with warfarin. The median CHA2DS2-VASc score was similar between warfarin and edoxaban 60 mg with a score of 3 (interquartile range [IQR] 2-4). In the inverse probability of treatment-weighted pseudo-population, the thromboembolic event rate for edoxaban 60 mg was 0.95 and 1.0 for warfarin, corresponding weighted HR of 1.00 (95% confidence intervals [CI] 0.59, 1.71). Edoxaban 60 mg users were associated with lower rates of all-cause mortality (3.93) compared to warfarin (6.04), with a HR of 0.64 (95% CI 0.47 to 0.88). The event rates for bleeding were 3.36 and 3.14, respectively; HR 1.09 (95% CI 0.77, 1.57) Conclusion: Edoxaban 60 mg is a safe and effective treatment compared with warfarin for stroke prevention in routine clinical care for white European patients with AF, with non-significantly different risks for stroke and clinically relevant bleeding, but lower all-cause mortality. 


Author(s):  
Hisashi Ogawa ◽  
Yoshimori An ◽  
Kenjiro Ishigami ◽  
Syuhei Ikeda ◽  
Kosuke Doi ◽  
...  

Abstract Aims Oral anticoagulants reduce the risk of ischaemic stroke but may increase the risk of major bleeding in atrial fibrillation (AF) patients. Little is known about the clinical outcomes of patients after a major bleeding event. This study assessed the outcomes of AF patients after major bleeding. Methods and results The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. Analyses were performed on 4304 AF patients registered by 81 institutions participating in the Fushimi AF Registry. We investigated the demographics and outcomes of AF patients who experienced major bleeding during follow-up period. During the median follow-up of 1307 days, major bleeding occurred in 297 patients (6.9%). Patients with major bleeding were older than those without (75.6 vs. 73.4 years; P < 0.01). They were more likely to have pre-existing heart failure (33.7% vs. 26.7%; P < 0.01), history of major bleeding (7.7% vs. 4.0%; P < 0.01), and higher mean HAS-BLED score (2.05 vs.1.73; P < 0.01). On landmark analysis, ischaemic stroke or systemic embolism occurred in 17 patients (3.6/100 person-years) after major bleeding and 227 patients (1.7/100 person-years) without major bleeding, with an adjusted hazard ratio (HR) of 1.93 [95% confidence interval (CI), 1.06–3.23; P = 0.03]. All-cause mortality occurred in 97 patients with major bleeding (20.0/100 person-years) and 709 (5.1/100 person-years) patients without major bleeding [HR 2.73 (95% CI, 2.16–3.41; P < 0.01)]. Conclusion In this community-based cohort, major bleeding is associated with increased risk of subsequent all-cause mortality and thromboembolism in the long-term amongst AF patients. Trial registration https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000005834. (last accessed 22 October 2020)


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
J Dickow ◽  
H.K Van Houten ◽  
L.R Sangaralingham ◽  
P.A Friedman ◽  
D.L Packer ◽  
...  

Abstract Background The Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST-AFNET 4) demonstrated clinical benefit of early rhythm-control therapy in patients with recently diagnosed atrial fibrillation (AF) and concomitant cardiovascular conditions (CHA2DS2-VASc-Score ≥2) compared to the current practice of limited rhythm-control therapy to improve AF-related symptoms. Purpose To evaluate the generalizability of the EAST-AFNET 4 trial in routine practice, we assessed the proportion of patients who would have met trial eligibility and examined the association between early rhythm-control and clinical outcomes. Methods Using a large US administrative database, we identified 109,739 patients with newly diagnosed AF from July 28th, 2011 to December 30th, 2016, the enrollment period of the EAST-AFNET 4 trial. Eligibility for trial inclusion was assessed based on inclusion criteria. Eligible patients were classified as either receiving early rhythm-control, i.e AF ablation and/or any antiarrhythmic drug therapy, within the first year after AF diagnosis (N=27,106) or patients not receiving early rhythm-control (N=82,633). The date 12 months after the first AF diagnosis was defined as the index date and the start of the follow up period. Propensity score overlap weighting was used to balance patients on 90 baseline characteristics. Cox proportional hazards regression was used to compare early rhythm-control with no early rhythm-control for the primary outcome of a composite end point of all-cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction. Results Eligible for the trial were 72.9% (82,633/109,739) of all patients with newly diagnosed AF. Early rhythm-control therapy was associated with a reduction in the composite end point in the overall cohort of patients (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.75–0.97; P=0.015) with largely consistent treatment effects between patients eligible or ineligible for the trial. The reduction of stroke risk associated with early rhythm-control therapy was found in the overall cohort (HR 0.66; 95% CI 0.47–0.93; P=0.017) and in the trial-eligible cohort (HR 0.67; 95% CI 0.45–0.98; P=0.041). Conclusion In a large health care data set, the majority of patients with newly diagnosed AF were eligible for the trial. Early rhythm-control therapy was associated with a 15% reduction in the composite end point of all-cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction, with the greatest benefit in the reduction of stroke risk. The treatment effect was consistent between patients eligible or ineligible for the trial. Patients in routine practice had higher rates of adverse outcomes than the trial, but the relative risk reduction with early rhythm-control therapy was similar. These data demonstrate the potential of early rhythm-control therapy to reduce outcomes in patients with AF. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): German Heart Foundation (Mit Fördermitteln der Deutschen Herzstiftung e.V.)


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y An ◽  
M Iguchi ◽  
M Ishii ◽  
N Masunaga ◽  
Y Aono ◽  
...  

Abstract Background Obesity has been shown to be related to an increased risk for incidence and progression of atrial fibrillation (AF). Meanwhile, the inverse association between body mass index (BMI) and mortality, so-called “obesity paradox”, is well-known among patients with AF, as well as other cardiovascular diseases. However, data regarding the relationship between BMI and specific causes of death in AF patients remain scarce. Methods The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto. The inclusion criterion for the registry is the documentation of AF at 12-lead electrocardiogram or Holter monitoring at any time. We started to enroll patients from March 2011, and baseline characteristics including BMI and follow-up data were available for 3,805 patients by the end of November 2018. Patients were categorized into 3 groups depending on the BMI value; underweight (<18.5 kg/m2; 419 patients), normal (18.5 to <25.0 kg/m2; 2,283 patients), overweight (≤25.0 kg/m2; 1,103 patients). Results In the entire population, the mean BMI level was 23.1±4.0 kg/m2. The lower BMI was associated with higher age (78.5±10.3, 74.0±10.3, and 71.3±10.9 years in Underweight, Normal, and Overweight, respectively; p<0.001) and with higher prevalence of various comorbidities and CHA2DS2-VASc scores (3.83±1.67, 3.43±1.70, and 3.29±1.64, p<0.001). Oral anticoagulants were less frequently prescribed in those with lower BMI (46%, 56%, and 58%, p<0.001). During a median follow-up of 1,464 days (interquartile range: 727–2,228 days), all-cause mortality was lower in accordance with higher BMI (14.3, 5.3, and 3.5 per 100 person-years, respectively; p<0.001). The proportion of infection as a cause of death was prominently higher in the Underweight group than the others (25.7%, 16.7%, and 13.4%, p<0.001) (Figure A). Furthermore, the mortality due to infection was consistently higher in Underweight than in the others in any of the age subgroups (Figure B). Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the BMI value for mortality, adjusted by age, sex, chronic kidney disease, anemia, chronic obstructive pulmonary disease, history of major bleeding, and other components of CHA2DS2-VASc score. Higher BMI was related to lower all-cause mortality (per 5 kg/m2 increase: HR 0.71 [95% CIs 0.63–0.78], p<0.001), and also lower mortality due to infection (per 5 kg/m2 increase: HR 0.48 [95% CIs 0.37–0.61], p<0.001). Figure 1 Conclusions In a Japanese community-based AF cohort, obesity paradox was also observed on all-cause mortality. In particular, lower BMI was strongly associated with the mortality due to infection regardless of age. Acknowledgement/Funding Boehringer Ingelheim, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Astellas Pharma, AstraZeneca, Daiichi-Sankyo, Novartis Pharma, MSD, Sanofi-Avent


2019 ◽  
Vol 14 (6) ◽  
pp. 873-881 ◽  
Author(s):  
Tsuyoshi Ohnishi ◽  
Miho Kimachi ◽  
Shingo Fukuma ◽  
Tadao Akizawa ◽  
Shunichi Fukuhara

Background and objectivesAlmost half of patients on dialysis demonstrate a postdialysis serum potassium ≤3.5 mEq/L. We aimed to examine the relationship between postdialysis potassium levels and all-cause mortality.Design, setting, patients, & measurementsWe conducted a cohort study of 3967 participants on maintenance hemodialysis from the Dialysis Outcomes and Practice Patterns Study in Japan (2009–2012 and 2012–2015). Postdialysis serum potassium was measured repeatedly at 4-month intervals and used as a time-varying variable. We estimated the hazard ratio of all-cause mortality rate using Cox hazard regression models, with and without adjusting for time-varying predialysis serum potassium. Models were adjusted for baseline characteristics and time-varying laboratory parameters. We also analyzed associations of combinations of pre- and postdialysis potassium with mortality.ResultsThe age of participants at baseline was 65±12 years (mean±SD), 2552 (64%) were men, and 96% were treated with a dialysate potassium level of 2.0 to <2.5 mEq/L. The median follow-up period was 2.6 (interquartile range, 1.3–2.8) years. During the follow-up period, 562 (14%) of 3967 participants died, and the overall mortality rate was 6.7 per 100 person-years. Compared with postdialysis potassium of 3.0 to <3.5 mEq/L, the hazard ratios of postdialysis hypokalemia (<3.0 mEq/L) were 1.84 (95% confidence interval, 1.44 to 2.34) in the unadjusted model, 1.44 (95% confidence interval, 1.14 to 1.82) in the model without adjusting for predialysis serum potassium, and 1.10 (95% confidence interval, 0.84 to 1.44) in the model adjusted for predialysis serum potassium. The combination of pre- and postdialysis hypokalemia was associated with the highest mortality risk (hazard ratio, 1.72; 95% confidence interval, 1.35 to 2.19, reference; pre- and postdialysis nonhypokalemia).ConclusionsPostdialysis hypokalemia was associated with mortality, but this association was not independent of predialysis potassium.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Surbhi Chamaria ◽  
Anand M. Desai ◽  
Pratap C. Reddy ◽  
Brian Olshansky ◽  
Paari Dominic

Introduction.Digoxin is used to control ventricular rate in atrial fibrillation (AF). There is conflicting evidence regarding safety of digoxin. We aimed to evaluate the risk of mortality with digoxin use in patients with AF using meta-analyses.Methods.PubMed was searched for studies comparing outcomes of patients with AF taking digoxin versus no digoxin, with or without heart failure (HF). Studies were excluded if they reported only a point estimate of mortality, duplicated patient populations, and/or did not report adjusted hazard ratios (HR). The primary endpoint was all-cause mortality. Adjusted HRs were combined using generic inverse variance and log hazard ratios. A multivariate metaregression model was used to explore heterogeneity in studies.Results.Twelve studies with 321,944 patients were included in the meta-analysis. In all AF patients, irrespective of heart failure status, digoxin is associated with increased all-cause mortality (HR [1.23], 95% confidence interval [CI] 1.16–1.31). However, digoxin is not associated with increased mortality in patients with AF and HF (HR [1.08], 95% CI 0.99–1.18). In AF patients without HF digoxin is associated with increased all-cause mortality (HR [1.38], 95% CI 1.12–1.71).Conclusion.In patients with AF and HF, digoxin use is not associated with an increased risk of all-cause mortality when used for rate control.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Apenteng ◽  
D.A Fitzmaurice ◽  
S Virdone ◽  
A.J Camm ◽  
K.A.A Fox ◽  
...  

Abstract Introduction Atrial fibrillation (AF) remains a common cause of stroke and anticoagulation (AC) treatment reduces the risk of stroke. Reasons for patients with AF not receiving anticoagulation are generally attributed to the clinician decision, however in reality a proportion of patients refuse anticoagulation. The aim of our study was to investigate the clinical outcomes of patients with AF who refused anticoagulation. Methods The Global Anticoagulant Registry in the FIELD (GARFIELD-AF) was an international prospective observational study of patients ≥18 years with newly diagnosed AF and ≥1 investigator determined risk factor for stroke. We analysed two-year outcomes (unadjusted) of non-haemorrhagic stroke/systemic embolism (stroke/SE), major bleeding and all-cause mortality in patients at high risk of stroke (men with CHA2DS2VASc≥2 and women with CHA2DS2VASc≥3) who did not received anticoagulation due to patient refusal, patients at high risk of stroke who received anticoagulation, and patients who were not on anticoagulation due to reasons other than patient refusal. Results Out of 43,154 patients, 13,283 (30.8%) are at the higher risk of stroke and did not received anticoagulation at baseline. The reason for not receiving anticoagulation was unavailable for 38.7% (5146/13283); of the patients with a known reason for not receiving anticoagulation, 12.5% (1014/8137) refused anticoagulation. Overall the study participants had a mean (SD) age of 72.2 (9.9) years and 50% were female. The median (Q1; Q3) CHA2DS2VASc score was 3.0 (3.0; 5.0) in patients who refused anticoagulation and 4.0 (3.0; 4.0) in patients who received anticoagulation. The median (Q1; Q3) HAS-BLED score was 1.0 (1.0; 2.0) in both groups. Of the patients who received anticoagulants, 59.7% received VKA and 40.3% received non-VKA oral anticoagulants. 79.4% of patients who refused anticoagulation were on antiplatelets. At two-year follow up the rate of events per 100 person-years (AC refused vs AC received) were: stroke/SE 1.42 vs 0.95 (p=0.04), major bleeding 0.62 vs 1.20 (p=0.02), and all-cause mortality 2.28 vs 3.90 (p=0.0004) (Figure). The event rates in patients who were not on anticoagulation for reasons other than patient refusal were stroke/SE 1.56, major bleeding 0.91, and all-cause mortality 5.49. Conclusion In this global real-world prospective study of patients with newly diagnosed AF, patients who refused anticoagulation had a higher rate of stroke/SE but lower rates of all-cause mortality and major bleeding than patients who received anticoagulation. While patient refusal of anticoagulation is an acceptable outcome of shared decision-making, clinically it is a missed opportunity to prevent AF related stroke. Patients' beliefs about AF related stroke and anticoagulation need to be explored. The difference in all-cause mortality warrants further investigation; further analysis will include adjusted results. Event rates at two years of follow-up Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): The GARFIELD-AF registry is funded by an unrestricted research grant from Bayer AG.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jelena Kornej ◽  
Qiuxi Huang ◽  
Sarah R. Preis ◽  
Steven A. Lubitz ◽  
Darae Ko ◽  
...  

Abstract Background All-cause mortality following atrial fibrillation (AF) has decreased over time. Data regarding temporal trends in causes of death among individuals with AF are scarce. The aim of our study was to analyze temporal trends in cause-specific mortality and predictors for cardiovascular (CVD) and non-CVD deaths among participants with incident AF in the Framingham Heart Study. Methods We categorized all newly diagnosed AF cases according to age at AF diagnosis (< 70, 70 to < 80, and ≥ 80 years) and epoch of AF diagnosis (< 1990, 1990–2002, and ≥ 2003). We followed participants until death or the last follow-up. We categorized death causes into CVD, non-CVD, and unknown causes. For each age group, we tested for trends in the cumulative incidence of cause-specific death across epochs. We fit multivariable Fine-Gray models to assess subdistribution hazard ratios (HR) between clinical risk factors at AF diagnosis and cause-specific mortality. Results We included 2125 newly diagnosed AF cases (mean age 75.5 years, 47.8% women). During a median follow-up of 4.8 years, 1657 individuals with AF died. There was evidence of decreasing CVD mortality among AF cases diagnosed < 70 years and 70 to < 80 years (ptrend < 0.001) but not ≥ 80 years (p = 0.76). Among the cases diagnosed < 70 years, the cumulative incidence of CVD death at 75 years was 67.7% in epoch 1 and 13.9% in epoch 3; among those 70 to < 80 years, the incidence at 85 years was 58.9% in epoch 1 and 18.9% in epoch 3. Advancing age (HR per 1 SD increase 6.33, 95% CI 5.44 to 7.37), prior heart failure (HR 1.49, 95% CI 1.14–1.94), and prior myocardial infarction (HR 1.44, 95% CI 1.15–1.80) were associated with increased rate of CVD death. Conclusions In this community-based cohort, CVD mortality among AF cases decreased over time. Most deaths in individuals with AF are no longer CVD-related, regardless of age at AF diagnosis.


2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaoxu Wang ◽  
Yi Luo ◽  
Dan Xu ◽  
Kun Zhao

Background: Whether digoxin is associated with increased mortality in atrial fibrillation (AF) remains controversial. We aimed to assess the risk of mortality and clinical effects of digoxin use in patients with AF.Methods: PubMed, Embase, and the Cochrane library were systematically searched to identify eligible studies comparing all-cause mortality of patients with AF taking digoxin with those not taking digoxin, and the length of follow-up was at least 6 months. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted and pooled.Results: A total of 29 studies with 621,478 patients were included. Digoxin use was associated with an increased risk of all-cause mortality in all patients with AF (HR 1.17, 95% CI 1.13–1.22, P &lt; 0.001), especially in patients without HF (HR 1.28, 95% CI 1.11–1.47, P &lt; 0.001). There was no significant association between digoxin and mortality in patients with AF and HF (HR 1.06, 95% CI 0.99–1.14, P = 0.110). In all patients with AF, regardless of concomitant HF, digoxin use was associated with an increased risk of sudden cardiac death (SCD) (HR 1.40, 95% CI 1.23–1.60, P &lt; 0.001) and cardiovascular (CV) mortality (HR 1.27, 95% CI 1.08–1.50, P &lt; 0.001), and digoxin use had no significant association with all-cause hospitalization (HR 1.13, 95% CI 0.92–1.39, P = 0.230).Conclusion: We conclude that digoxin use is associated with an increased risk of all-cause mortality, CV mortality, and SCD, and it does not reduce readmission for AF, regardless of concomitant HF. Digoxin may have a neutral effect on all-cause mortality in patients with AF with concomitant HF.Systematic Review Registration:https://www.crd.york.ac.ukPROSPERO.


2021 ◽  
Vol 11 (11) ◽  
pp. 1202
Author(s):  
Hsing-Yu Chen ◽  
John Malik ◽  
Hau-Tieng Wu ◽  
Chun-Li Wang

Background: The application of heart rate variability is problematic in patients with atrial fibrillation (AF). This study aims to explore the associations between all-cause mortality and the median hourly ambulatory heart rate range (AHRR˜24hr) compared with other parameters obtained from the Holter monitor in patients with newly diagnosed AF. Material and Methods: A total of 30 parameters obtained from 521 persistent AF patients’ Holter monitor were analyzed retrospectively from 1 January 2010 to 31 July 2014. Every patient was followed up to the occurrence of death or the end of 30 June 2017. Results:AHRR˜24hr was the most feasible Holter parameter. Lower AHRR˜24hr was associated with increased risk of all-cause mortality (adjusted hazard ratio [aHR] for every 10-bpm reduction: 2.70, 95% confidence interval [CI]: 1.75–4.17, p < 0.001). The C-statistic of AHRR˜24hr alone was 0.707 (95% CI: 0.658–0.756), and 0.697 (95% CI: 0.650–0.744) for the CHA2DS2-VASc score alone. By combining AHRR˜24hr with the CHA2DS2-VASc score, the C-statistic could improve to 0.764 (95% CI: 0.722–0.806). While using 20 bpm as the cut-off value, the aHR was 3.66 (95% CI: 2.05–6.52) for patients with AHRR˜24hr < 20 bpm in contrast to patients with AHRR˜24hr ≥ 20 bpm. Conclusions:AHRR˜24hr could be helpful for risk stratification for AF in addition to the CHA2DS2-VASc score.


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