Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist as they share multiple risk factors, including hypertension, diabetes mellitus, and coronary artery disease. Although there is ...irrefutable evidence supporting anticoagulation in AF in the general population, these data may not be transferable to the setting of advanced CKD, where the decision to commence anticoagulation poses a conundrum. In this cohort, there is a progressively increased risk of both ischemic stroke and hemorrhage as renal function declines, complicating the decision to initiate anticoagulation. No definitive clinical guidelines derived from randomized controlled trials exist to aid clinical decision-making, and the findings from observational studies are conflicting. In this review, the authors outline the pathophysiological mechanisms at play and summarize the limited existing data related to anticoagulation in those with concomitant CKD and AF. Finally, the authors suggest how to approach the decision of whether and how to use oral anticoagulation in these patients.
Atrial fibrillation (AF) is common in older people with frailty and is associated with an increased risk of stroke and systemic embolism. Whilst oral anticoagulation is associated with a reduction in ...this risk, there is a lack of data on the safety and efficacy of direct oral anticoagulants (DOACs) in people with frailty. This study aims to report clinical outcomes of patients with AF in the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial by frailty status.
Post hoc analysis of 20,867 participants in the ENGAGE AF-TIMI 48 trial, representing 98.8% of those randomised. This double-blinded double-dummy trial compared two once-daily regimens of edoxaban (a DOAC) with warfarin. Participants were categorised as fit, living with pre-frailty, mild-moderate, or severe frailty according to a standardised index, based upon the cumulative deficit model. The primary efficacy endpoint was stroke or systemic embolism and the safety endpoint was major bleeding.
A fifth (19.6%) of the study population had frailty (fit: n = 4459, pre-frailty: n = 12,326, mild-moderate frailty: n = 3722, severe frailty: n = 360). On average over the follow-up period, the risk of stroke or systemic embolism increased by 37% (adjusted HR 1.37, 95% CI 1.19-1.58) and major bleeding by 42% (adjusted HR 1.42, 1.27-1.59) for each 0.1 increase in the frailty index (four additional health deficits). Edoxaban was associated with similar efficacy to warfarin in every frailty category, and a lower risk of bleeding than warfarin in all but those living with severe frailty.
Edoxaban was similarly efficacious to warfarin across the frailty spectrum and was associated with lower rates of bleeding except in those with severe frailty. Overall, with increasing frailty, there was an increase in stroke and bleeding risk. There is a need for high-quality, frailty-specific population randomised control trials to guide therapy in this vulnerable population.
ClinicalTrials.gov NCT00781391 . First registered on 28 October 2008.
Abstract
Aims
To determine whether changing patterns of anticoagulant use in atrial fibrillation (AF) have impacted on stroke rates in England.
Methods and results
English national databases, ...2006–2016, were interrogated to assess stroke admissions and oral anticoagulant use. The number of patients with known AF increased linearly from 692 054 to 983 254 (prevalence 1.29% vs. 1.71%). Hospital episodes of AF-related stroke/100 000 AF patients increased from 80/week in 2006 to 98/week in 2011 and declined to 86/week in 2016 (2006–2011 difference 18.0, 95% confidence interval (CI) 17.9–18.1, 2011–2016 difference −12.0, 95% CI −12.1 to −11.9). Anticoagulant use amongst patients with CHA2DS2-VASc ≥2 increased from 48.0% to 78.6% and anti-platelet use declined from 42.9% to 16.1%; the greatest rate of change occurred in the second 5 year period (for anticoagulants 2006–2011 difference 4.8%, 95% CI 4.5–5.1%, 2011–2016 difference 25.8%, 95% CI 25.5–26.1%). After adjustment for AF prevalence, a 1% increase in anticoagulant use was associated with a 0.8% decrease in the weekly rate of AF-related stroke (incidence rate ratio 0.992, 95% CI 0.989–0.994). Had the use of anticoagulants remained at 2009 levels, 4068 (95% CI 4046–4089) more strokes would have been predicted in 2015/2016.
Conclusion
Between 2006 and 2016, AF prevalence and anticoagulant use in England increased. From 2011, hospitalized AF-related stroke rates declined and were significantly associated with increased anticoagulant uptake.
Abstract Background For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if β-blockers are associated with reduced mortality. Objectives The goal of this study was to ...determine the association between β-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD). Methods This cohort study used national English and Welsh registry data from the Myocardial Ischaemia National Audit Project. A total of 179,810 survivors of hospitalization with AMI without HF or LVSD, between January 1, 2007, and June 30, 2013 (final follow-up: December 31, 2013), were assessed. Survival-time inverse probability weighting propensity scores and instrumental variable analyses were used to investigate the association between the use of β-blockers and 1-year mortality. Results Of 91,895 patients with ST-segment elevation myocardial infarction and 87,915 patients with non–ST-segment elevation myocardial infarction, 88,542 (96.4%) and 81,933 (93.2%) received β-blockers, respectively. For the entire cohort, with >163,772 person-years of observation, there were 9,373 deaths (5.2%). Unadjusted 1-year mortality was lower for patients who received β-blockers compared with those who did not (4.9% vs. 11.2%; p < 0.001). However, after weighting and adjustment, there was no significant difference in mortality between those with and without β-blocker use (average treatment effect ATE coefficient: 0.07; 95% confidence interval CI: −0.60 to 0.75; p = 0.827). Findings were similar for ST-segment elevation myocardial infarction (ATE coefficient: 0.30; 95% CI: −0.98 to 1.58; p = 0.637) and non–ST-segment elevation myocardial infarction (ATE coefficient: −0.07; 95% CI: −0.68 to 0.54; p = 0.819). Conclusions Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of β-blockers was not associated with a lower risk of death at any time point up to 1 year. (β-Blocker Use and Mortality in Hospital Survivors of Acute Myocardial Infarction Without Heart Failure; NCT02786654 )
Background
This study assessed sex differences in treatments, all‐cause mortality, relative survival, and excess mortality following acute myocardial infarction.
Methods and Results
A ...population‐based cohort of all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART Swedish Web System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies) from 2003 to 2013 was included in the analysis. Excess mortality rate ratios (EMRRs), adjusted for clinical characteristics and guideline‐indicated treatments after matching by age, sex, and year to background mortality data, were estimated. Although there were no sex differences in all‐cause mortality adjusted for age, year of hospitalization, and comorbidities for ST‐segment–elevation myocardial infarction (STEMI) and non‐STEMI at 1 year (mortality rate ratio: 1.01 95% confidence interval (CI), 0.96–1.05 and 0.97 95% CI, 0.95–0.99, respectively) and 5 years (mortality rate ratio: 1.03 95% CI, 0.99–1.07 and 0.97 95% CI, 0.95–0.99, respectively), excess mortality was higher among women compared with men for STEMI and non‐STEMI at 1 year (EMRR: 1.89 95% CI, 1.66–2.16 and 1.20 95% CI, 1.16–1.24, respectively) and 5 years (EMRR: 1.60 95% CI, 1.48–1.72 and 1.26 95% CI, 1.21–1.32, respectively). After further adjustment for the use of guideline‐indicated treatments, excess mortality among women with non‐STEMI was not significant at 1 year (EMRR: 1.01 95% CI, 0.97–1.04) and slightly higher at 5 years (EMRR: 1.07 95% CI, 1.02–1.12). For STEMI, adjustment for treatments attenuated the excess mortality for women at 1 year (EMRR: 1.43 95% CI, 1.26–1.62) and 5 years (EMRR: 1.31 95% CI, 1.19–1.43).
Conclusions
Women with acute myocardial infarction did not have statistically different all‐cause mortality, but had higher excess mortality compared with men that was attenuated after adjustment for the use of guideline‐indicated treatments. This suggests that improved adherence to guideline recommendations for the treatment of acute myocardial infarction may reduce premature cardiovascular death among women.
Clinical Trial Registration
URL: https://www.clinicaltrials.gov. Unique identifier: NCT02952417.
Background Studies have reported significant reduction in acute myocardial infarction-related hospitalizations during the coronavirus disease 2019 (COVID-19) pandemic. However, whether these trends ...are associated with increased incidence of out-of-hospital cardiac arrest (OHCA) in this population is unknown. Methods and Results Acute myocardial infarction hospitalizations with OHCA during the COVID-19 period (February 1-May 14, 2020) from the Myocardial Ischaemia National Audit Project and British Cardiovascular Intervention Society data sets were analyzed. Temporal trends were assessed using Poisson models with equivalent pre-COVID-19 period (February 1-May 14, 2019) as reference. Acute myocardial infarction hospitalizations during COVID-19 period were reduced by >50% (n=20 310 versus n=9325). OHCA was more prevalent during the COVID-19 period compared with the pre-COVID-19 period (5.6% versus 3.6%), with a 56% increase in the incidence of OHCA (incidence rate ratio, 1.56; 95% CI, 1.39-1.74). Patients experiencing OHCA during COVID-19 period were likely to be older, likely to be women, likely to be of Asian ethnicity, and more likely to present with ST-segment-elevation myocardial infarction. The overall rates of invasive coronary angiography (58.4% versus 71.6%;
<0.001) were significantly lower among the OHCA group during COVID-19 period with increased time to reperfusion (mean, 2.1 versus 1.1 hours;
=0.05) in those with ST-segment-elevation myocardial infarction. The adjusted in-hospital mortality probability increased from 27.7% in February 2020 to 35.8% in May 2020 in the COVID-19 group (
<.001). Conclusions In this national cohort of hospitalized patients with acute myocardial infarction, we observed a significant increase in incidence of OHCA during COVID-19 period paralleled with reduced access to guideline-recommended care and increased in-hospital mortality.
Abstract
Aims
The effect of the COVID-19 pandemic on care and outcomes across non-COVID-19 cardiovascular (CV) diseases is unknown. A systematic review and meta-analysis was performed to quantify the ...effect and investigate for variation by CV disease, geographic region, country income classification and the time course of the pandemic.
Methods and results
From January 2019 to December 2021, Medline and Embase databases were searched for observational studies comparing a pandemic and pre-pandemic period with relation to CV disease hospitalisations, diagnostic and interventional procedures, outpatient consultations, and mortality. Observational data were synthesised by incidence rate ratios (IRR) and risk ratios (RR) for binary outcomes and weighted mean differences for continuous outcomes with 95% confidence intervals. The study was registered with PROSPERO (CRD42021265930). A total of 158 studies, covering 49 countries and 6 continents, were used for quantitative synthesis. Most studies (80%) reported information for high-income countries (HICs). Across all CV disease and geographies there were fewer hospitalisations, diagnostic and interventional procedures, and outpatient consultations during the pandemic. By meta-regression, in low-middle income countries (LMICs) compared to HICs the decline in ST-segment elevation myocardial infarction (STEMI) hospitalisations (RR 0.79, 95% confidence interval CI 0.66–0.94) and revascularisation (RR 0.73, 95% CI 0.62–0.87) was more severe. In LMICs, but not HICs, in-hospital mortality increased for STEMI (RR 1.22, 95% CI 1.10–1.37) and heart failure (RR 1.08, 95% CI 1.04–1.12). The magnitude of decline in hospitalisations for CV diseases did not differ between the first and second wave.
Conclusions
There was substantial global collateral CV damage during the COVID-19 pandemic with disparity in severity by country income classification.
Structured Graphical Abstract
Structured Graphical Abstract
Major findings of the collateral damage of the COVID-19 pandemic on cardiovascular services. Abbreviations in text.
Audio Abstract
10.1093/eurheartj/ehac227_audio1
Audio Abstract
ehac227audio1
6306947121112
To describe the place and cause of death during the coronavirus disease 2019 (COVID-19) pandemic to assess its impact on excess mortality.
This national death registry included all adult (aged ≥18 ...years) deaths in England and Wales between January 1, 2014, and June 30, 2020. Daily deaths during the COVID-19 pandemic were compared against the expected daily deaths, estimated with use of the Farrington surveillance algorithm for daily historical data between 2014 and 2020 by place and cause of death.
Between March 2 and June 30, 2020, there was an excess mortality of 57,860 (a proportional increase of 35%) compared with the expected deaths, of which 50,603 (87%) were COVID-19 related. At home, only 14% (2267) of the 16,190 excess deaths were related to COVID-19, with 5963 deaths due to cancer and 2485 deaths due to cardiac disease, few of which involved COVID-19. In care homes or hospices, 61% (15,623) of the 25,611 excess deaths were related to COVID-19, 5539 of which were due to respiratory disease, and most of these (4315 deaths) involved COVID-19. In the hospital, there were 16,174 fewer deaths than expected that did not involve COVID-19, with 4088 fewer deaths due to cancer and 1398 fewer deaths due to cardiac disease than expected.
The COVID-19 pandemic has resulted in a large excess of deaths in care homes that were poorly characterized and likely to be the result of undiagnosed COVID-19. There was a smaller but important and ongoing excess in deaths at home, particularly from cancer and cardiac disease, suggesting public avoidance of hospital care for non-COVID-19 conditions.
The occurrence of a range of health outcomes following myocardial infarction (MI) is unknown. Therefore, this study aimed to determine the long-term risk of major health outcomes following MI and ...generate sociodemographic stratified risk charts in order to inform care recommendations in the post-MI period and underpin shared decision making.
This nationwide cohort study includes all individuals aged ≥18 years admitted to one of 229 National Health Service (NHS) Trusts in England between 1 January 2008 and 31 January 2017 (final follow-up 27 March 2017). We analysed 11 non-fatal health outcomes (subsequent MI and first hospitalisation for heart failure, atrial fibrillation, cerebrovascular disease, peripheral arterial disease, severe bleeding, renal failure, diabetes mellitus, dementia, depression, and cancer) and all-cause mortality. Of the 55,619,430 population of England, 34,116,257 individuals contributing to 145,912,852 hospitalisations were included (mean age 41.7 years (standard deviation SD 26.1); n = 14,747,198 (44.2%) male). There were 433,361 individuals with MI (mean age 67.4 years SD 14.4); n = 283,742 (65.5%) male). Following MI, all-cause mortality was the most frequent event (adjusted cumulative incidence at 9 years 37.8% (95% confidence interval CI 37.6,37.9), followed by heart failure (29.6%; 95% CI 29.4,29.7), renal failure (27.2%; 95% CI 27.0,27.4), atrial fibrillation (22.3%; 95% CI 22.2,22.5), severe bleeding (19.0%; 95% CI 18.8,19.1), diabetes (17.0%; 95% CI 16.9,17.1), cancer (13.5%; 95% CI 13.3,13.6), cerebrovascular disease (12.5%; 95% CI 12.4,12.7), depression (8.9%; 95% CI 8.7,9.0), dementia (7.8%; 95% CI 7.7,7.9), subsequent MI (7.1%; 95% CI 7.0,7.2), and peripheral arterial disease (6.5%; 95% CI 6.4,6.6). Compared with a risk-set matched population of 2,001,310 individuals, first hospitalisation of all non-fatal health outcomes were increased after MI, except for dementia (adjusted hazard ratio aHR 1.01; 95% CI 0.99,1.02;p = 0.468) and cancer (aHR 0.56; 95% CI 0.56,0.57;p < 0.001). The study includes data from secondary care only-as such diagnoses made outside of secondary care may have been missed leading to the potential underestimation of the total burden of disease following MI.
In this study, up to a third of patients with MI developed heart failure or renal failure, 7% had another MI, and 38% died within 9 years (compared with 35% deaths among matched individuals). The incidence of all health outcomes, except dementia and cancer, was higher than expected during the normal life course without MI following adjustment for age, sex, year, and socioeconomic deprivation. Efforts targeted to prevent or limit the accrual of chronic, multisystem disease states following MI are needed and should be guided by the demographic-specific risk charts derived in this study.
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