Publications by authors named "Gregory Y H Lip"

2,323 Publications

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Association of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies.

BMC Med 2021 Jun 22;19(1):139. Epub 2021 Jun 22.

Head Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz (MUL), Lodz, Poland.

Background: Current evidence from randomized controlled trials on statins for primary prevention of cardiovascular disease (CVD) in older people, especially those aged > 75 years, is still lacking. We conducted a systematic review and meta-analysis of observational studies to extend the current evidence about the association of statin use in older people primary prevention group with risk of CVD and mortality.

Methods: PubMed, Scopus, and Embase were searched from inception until March 18, 2021. We included observational studies (cohort or nested case-control) that compared statin use vs non-use for primary prevention of CVD in older people aged ≥ 65 years; provided that each of them reported the risk estimate on at least one of the following primary outcomes: all cause-mortality, CVD death, myocardial infarction (MI), and stroke. Risk estimates of each relevant outcome were pooled as a hazard ratio (HR) with a 95% confidence interval (CI) using the random-effects meta-analysis model. The quality of the evidence was rated using the GRADE approach.

Results: Ten observational studies (9 cohorts and one case-control study; n = 815,667) fulfilled our criteria. The overall combined estimate suggested that statin therapy was associated with a significantly lower risk of all-cause mortality (HR: 0.86 [95% CI 0.79 to 0.93]), CVD death (HR: 0.80 [95% CI 0.78 to 0.81]), and stroke (HR: 0.85 [95% CI 0.76 to 0.94]) and a non-significant association with risk of MI (HR 0.74 [95% CI 0.53 to 1.02]). The beneficial association of statins with the risk of all-cause mortality remained significant even at higher ages (> 75 years old; HR 0.88 [95% CI 0.81 to 0.96]) and in both men (HR: 0.75 [95% CI: 0.74 to 0.76]) and women (HR 0.85 [95% CI 0.72 to 0.99]). However, this association with the risk of all-cause mortality remained significant only in those with diabetes mellitus (DM) (HR 0.82 [95% CI 0.68 to 0.98]) but not in those without DM. The level of evidence of all the primary outcomes was rated as "very low."

Conclusions: Statin therapy in older people (aged ≥ 65 years) without CVD was associated with a 14%, 20%, and 15% lower risk of all-cause mortality, CVD death, and stroke, respectively. The beneficial association with the risk of all-cause mortality remained significant even at higher ages (> 75 years old), in both men and women, and in individuals with DM, but not in those without DM. These observational findings support the need for trials to test the benefits of statins in those above 75 years of age.
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http://dx.doi.org/10.1186/s12916-021-02009-1DOI Listing
June 2021

Exercise-based cardiac rehabilitation for cardiac implantable electronic device recipients.

Eur J Prev Cardiol 2021 Jun 21. Epub 2021 Jun 21.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK.

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http://dx.doi.org/10.1093/eurjpc/zwab103DOI Listing
June 2021

How effective is pharmacotherapy for stroke and what more is needed? A focus on atrial fibrillation.

Expert Opin Pharmacother 2021 Jun 19:1-4. Epub 2021 Jun 19.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK.

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http://dx.doi.org/10.1080/14656566.2021.1921738DOI Listing
June 2021

The Atrial Fibrillation Better Care pathway for managing atrial fibrillation: a review.

Europace 2021 Jun 14. Epub 2021 Jun 14.

Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool Heart & Chest Hospital, 6 West Derby Street, Liverpool L7 8TX, UK.

The 2020 European Society of Cardiology guidelines endorse the Atrial Fibrillation Better Care (ABC) pathway as a structured approach for the management of atrial fibrillation (AF), addressing three principal elements: 'A' - avoid stroke (with oral anticoagulation), 'B' - patient-focused better symptom management, and 'C' - cardiovascular and comorbidity risk factor reduction and management. This review summarizes the definitions used for the ABC criteria in different studies and the impact of adherence/non-adherence on clinical outcomes, from 12 studies on seven different cohorts. All studies consistently showed statistically significant reductions in the risk of stroke, myocardial infarction, and mortality among those with ABC pathway adherent treatment. The ABC pathway provides a simple decision-making framework to enable consistent equitable care from clinicians in primary and secondary/tertiary care. Further research examining the impact of ABC pathway implementation in prospective cohorts utilizing consistent inclusion criteria and definitions of 'A', 'B', and 'C' adherent care is warranted.
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http://dx.doi.org/10.1093/europace/euab092DOI Listing
June 2021

Low bleeding and thromboembolic risk with continued dabigatran during cardiovascular interventions: the GLORIA-AF study.

Eur J Intern Med 2021 Jun 11. Epub 2021 Jun 11.

Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.

Background: Prospective data on nonvitamin-K-antagonist oral anticoagulant (NOAC) management during cardiovascular interventions are limited. We therefore evaluated the safety and effectiveness of uninterrupted dabigatran therapy as well as dabigatran management during atrial fibrillation (AF)-cardioversions, AF-ablations, pacemaker implantations and coronary angiography and/or stenting procedures.

Method: GLORIA-AF is an international registry programme involving patients with newly diagnosed AF. Dabigatran users were followed for ≤2 years. The primary outcome was occurrence of stroke/systemic embolism and major bleeding ≤8 weeks after a cardiovascular intervention during uninterrupted dabigatran therapy.

Results: During the 2-year follow-up, 599 cardiovascular interventions were identified in 479 eligible patients. 412/599 (69%) interventions were performed with uninterrupted dabigatran therapy: 299/354 (84%) AF-cardioversions, 38/89 (43%) AF-ablations, 25/58 (43%) pacemaker implantations, and 50/98 (51%) coronary angiography and/or stenting procedures. During an average follow-up of 8.4 weeks after intervention, one major bleed and one systemic embolic event occurred (risk 0.25% for both outcomes; 95% confidence interval, 0.01%-1.36%).

Conclusions: More than two thirds of the interventions were performed with uninterrupted dabigatran therapy, of which most were AF-cardioversions. Uninterrupted dabigatran therapy was associated with low major bleeding and stroke/systemic embolism risk, supporting the favourable safety and effectiveness profile of dabigatran in clinical practice-based settings.
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http://dx.doi.org/10.1016/j.ejim.2021.05.020DOI Listing
June 2021

Bleeding complications in patients with gastrointestinal cancer and atrial fibrillation treated with oral anticoagulants.

Cancer Med 2021 Jun 11. Epub 2021 Jun 11.

Unit for Thrombosis and Drug Research, Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

Background: Direct oral anticoagulants (DOACs) may increase the risk of gastrointestinal (GI) bleeding in patients with atrial fibrillation (AF) and GI cancer compared with vitamin K antagonists (VKA).

Methods: We conducted a Danish nationwide cohort study comparing the bleeding risk associated with DOAC versus VKA in patients with AF and GI cancer. We calculated crude bleeding rates per 100 person-years (PYs) for GI and major bleeding. We then compared rates of bleeding at 1 year after initial oral anticoagulation filled prescription by treatment regimen using inverse probability of treatment weighting and Cox regression.

Results: The unweighted study population included 1476 AF patients with GI cancer (41.6% women, median age 78 years) initiating a DOAC and 652 initiating a VKA. One-year risk of GI bleeding was 5.0% in the DOAC group and 4.7% in the VKA group with a corresponding weighted hazard ratio (HR) of 0.95 (95% confidence interval [CI]: 0.63, 1.45). For patients with active cancer, weighted GI bleeding rates were slightly higher in both the VKA and DOAC group, and the weighted HR was 1.00 (95% CI: 0.53, 1.88). The HR was 1.12 (95% CI: 0.71, 1.76) for all bleedings. Hazard ratios for GI bleeding were 0.61 (95% CI: 0.25, 1.52) for patients with upper GI cancer, and 0.92 (95% CI: 0.58, 1.46) in patients with colorectal cancer.

Conclusion: Evidence from this nationwide cohort study suggests a comparable 1-year risk of bleeding associated with DOAC compared with VKA among patients with AF and GI cancer.
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http://dx.doi.org/10.1002/cam4.4012DOI Listing
June 2021

Associations of hypertension burden on subsequent dementia: a population-based cohort study.

Sci Rep 2021 Jun 10;11(1):12291. Epub 2021 Jun 10.

Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

In this nationwide cohort study, we assessed the effects of hypertension burden and blood pressure (BP) control on dementia in different age subgroups. From the Korean National Health Insurance Service-Health Screening cohort from January 1, 2005 to December 31, 2013, we enrolled 428,976 subjects aged 40-79 years without previous diagnosis of dementia or stroke. During a mean follow-up of 7.3 ± 1.5 years, 9435 (2.2%) were diagnosed with dementia. Per 10 mmHg increase in systolic BP (SBP), risk of dementia was increased by 22% (95% confidence interval [CI] 1.15-1.30) in subjects aged 40-59 years and 8% (95% CI 1.04-1.11) in subjects aged 60-69 years. No significant associations were observed in subjects aged ≥ 70 years. Among subjects aged 40-59 years, both vascular and Alzheimer's dementia risks were increased with increasing SBP. Increasing hypertension burden (proportion of days with increased BP) was associated with higher dementia risk (hazard ratio [HR] 1.09 per 10% increase, 95% CI 1.08-1.10). Among patients with baseline SBP ≥ 140 mmHg, optimal follow-up SBP (120-139 mmHg) was associated with decreased dementia risk (HR 0.69, 95% CI 0.50-0.95). Hypertension burden was associated with higher risks of dementia. Adequate BP control was associated with lower risk of dementia in individuals aged < 70 years.
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http://dx.doi.org/10.1038/s41598-021-91923-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192762PMC
June 2021

Cardiovascular risk factors, cardiovascular disease, and COVID-19: an umbrella review of systematic reviews.

Eur Heart J Qual Care Clin Outcomes 2021 Jun 9. Epub 2021 Jun 9.

Liverpool Centre for Cardiovascular Science, University of Liverpool & Liverpool Heart and Chest Hospital, William Henry Duncan Building, 6 West Derby Street, Liverpool L7 8TX, UK.

Aims: To consolidate evidence to determine (i) the association between cardiovascular risk factors and health outcomes with coronavirus 2019 (COVID-19); and (ii) the impact of COVID-19 on cardiovascular health.

Methods And Results: An umbrella review of systematic reviews was conducted. Fourteen medical databases and pre-print servers were searched from 1 January 2020 to 5 November 2020. The review focused on reviews rated as moderate or high-quality using the AMSTAR 2 tool. Eighty-four reviews were identified; 31 reviews were assessed as moderate quality and one was high-quality. The following risk factors were associated with higher mortality and severe COVID-19: renal disease [odds ratio (OR) (95% confidence interval) for mortality 3.07 (2.43-3.88)], diabetes mellitus [OR 2.09 (1.80-2.42)], hypertension [OR 2.50 (2.02-3.11)], smoking history [risk ratio (RR) 1.26 (1.20-1.32)], cerebrovascular disease [RR 2.75 (1.54-4.89)], and cardiovascular disease [OR 2.65 (1.86-3.78)]. Liver disease was associated with higher odds of mortality [OR 2.81 (1.31-6.01)], but not severe COVID-19. Current smoking was associated with a higher risk of severe COVID-19 [RR 1.80 (1.14-2.85)], but not mortality. Obesity associated with higher odds of mortality [OR 2.18 (1.10-4.34)], but there was an absence of evidence for severe COVID-19. In patients hospitalized with COVID-19, the following incident cardiovascular complications were identified: acute heart failure (2%), myocardial infarction (4%), deep vein thrombosis (7%), myocardial injury (10%), angina (10%), arrhythmias (18%), pulmonary embolism (19%), and venous thromboembolism (25%).

Conclusion: Many of the risk factors identified as associated with adverse outcomes with COVID-19 are potentially modifiable. Primary and secondary prevention strategies that target cardiovascular risk factors may improve outcomes for people following COVID-19.
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http://dx.doi.org/10.1093/ehjqcco/qcab029DOI Listing
June 2021

Association between exercise habits and stroke, heart failure, and mortality in Korean patients with incident atrial fibrillation: A nationwide population-based cohort study.

PLoS Med 2021 Jun 8;18(6):e1003659. Epub 2021 Jun 8.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: There is a paucity of information about cardiovascular outcomes related to exercise habit change after a new diagnosis of atrial fibrillation (AF). We investigated the association between exercise habits after a new AF diagnosis and ischemic stroke, heart failure (HF), and all-cause death.

Methods And Findings: This is a nationwide population-based cohort study using data from the Korea National Health Insurance Service. A retrospective analysis was performed for 66,692 patients with newly diagnosed AF between 2010 and 2016 who underwent 2 serial health examinations within 2 years before and after their AF diagnosis. Individuals were divided into 4 categories according to performance of regular exercise, which was investigated by a self-reported questionnaire in each health examination, before and after their AF diagnosis: persistent non-exercisers (30.5%), new exercisers (17.8%), exercise dropouts (17.4%), and exercise maintainers (34.2%). The primary outcomes were incidence of ischemic stroke, HF, and all-cause death. Differences in baseline characteristics among groups were balanced considering demographics, comorbidities, medications, lifestyle behaviors, and income status. The risks of the outcomes were computed by weighted Cox proportional hazards models with inverse probability of treatment weighting (IPTW) during a mean follow-up of 3.4 ± 2.0 years. The new exerciser and exercise maintainer groups were associated with a lower risk of HF compared to the persistent non-exerciser group: the hazard ratios (HRs) (95% CIs) were 0.95 (0.90-0.99) and 0.92 (0.88-0.96), respectively (p < 0.001). Also, performing exercise any time before or after AF diagnosis was associated with a lower risk of mortality compared to persistent non-exercising: the HR (95% CI) was 0.82 (0.73-0.91) for new exercisers, 0.83 (0.74-0.93) for exercise dropouts, and 0.61 (0.55-0.67) for exercise maintainers (p < 0.001). For ischemic stroke, the estimates of HRs were 10%-14% lower in patients of the exercise groups, yet differences were statistically insignificant (p = 0.057). Energy expenditure of 1,000-1,499 MET-min/wk (regular moderate exercise 170-240 min/wk) was consistently associated with a lower risk of each outcome based on a subgroup analysis of the new exerciser group. Study limitations include recall bias introduced due to the nature of the self-reported questionnaire and restricted external generalizability to other ethnic groups.

Conclusions: Initiating or continuing regular exercise after AF diagnosis was associated with lower risks of HF and mortality. The promotion of exercise might reduce the future risk of adverse outcomes in patients with AF.
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http://dx.doi.org/10.1371/journal.pmed.1003659DOI Listing
June 2021

Lower risk of stroke after alcohol abstinence in patients with incident atrial fibrillation: a nationwide population-based cohort study.

Eur Heart J 2021 Jun 7. Epub 2021 Jun 7.

Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.

Aims: The aim of this study was to evaluate the association between alcohol consumption status (and its changes) after newly diagnosed atrial fibrillation (AF) and the risk of ischaemic stroke.

Methods And Results: Using the Korean nationwide claims and health examination database, we included subjects who were newly diagnosed with AF between 2010 and 2016. Patients were categorized into three groups according to the status of alcohol consumption before and after AF diagnosis: non-drinkers; abstainers from alcohol after AF diagnosis; and current drinkers. The primary outcome was incident ischaemic stroke during follow-up. Non-drinkers, abstainers, and current drinkers were compared using incidence rate differences after the inverse probability of treatment weighting (IPTW). Among a total of 97 869 newly diagnosed AF patients, 51% were non-drinkers, 13% were abstainers, and 36% were current drinkers. During 310 926 person-years of follow-up, 3120 patients were diagnosed with incident ischaemic stroke (10.0 per 1000 person-years). At 5-year follow-up, abstainers and non-drinkers were associated with a lower risk for stroke than current drinkers (incidence rate differences after IPTW, -2.03 [-3.25, -0.82] for abstainers and -2.98 [-3.81, -2.15] for non-drinkers, per 1000 person-years, respectively; and incidence rate ratios after IPTW, 0.75 [0.70, 0.81] for non-drinkers and 0.83 [0.74, 0.93] for abstainers, respectively).

Conclusion : Current alcohol consumption was associated with an increased risk of ischaemic stroke in patients with newly diagnosed AF, and alcohol abstinence after AF diagnosis could reduce the risk of ischaemic stroke. Lifestyle intervention, including attention to alcohol consumption, should be encouraged as part of a comprehensive approach to AF management to improve clinical outcomes.
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http://dx.doi.org/10.1093/eurheartj/ehab315DOI Listing
June 2021

Exercise-Based Cardiac Rehabilitation and All-Cause Mortality Among Patients With Atrial Fibrillation.

J Am Heart Assoc 2021 Jun 5;10(12):e020804. Epub 2021 Jun 5.

Liverpool Centre for Cardiovascular Science University of Liverpool and Liverpool Heart & Chest Hospital Liverpool United Kingdom.

Background There is limited evidence of long-term impact of exercise-based cardiac rehabilitation (CR) on clinical end points for patients with atrial fibrillation (AF). We therefore compared 18-month all-cause mortality, hospitalization, stroke, and heart failure in patients with AF and an electronic medical record of exercise-based CR to matched controls. Methods and Results This retrospective cohort study included patient data obtained on February 3, 2021 from a global federated health research network. Patients with AF undergoing exercise-based CR were propensity-score matched to patients with AF without exercise-based CR by age, sex, race, comorbidities, cardiovascular procedures, and cardiovascular medication. We ascertained 18-month incidence of all-cause mortality, hospitalization, stroke, and heart failure. Of 1 366 422 patients with AF, 11 947 patients had an electronic medical record of exercise-based CR within 6-months of incident AF who were propensity-score matched with 11 947 patients with AF without CR. Exercise-based CR was associated with 68% lower odds of all-cause mortality (odds ratio, 0.32; 95% CI, 0.29-0.35), 44% lower odds of rehospitalization (0.56; 95% CI, 0.53-0.59), and 16% lower odds of incident stroke (0.84; 95% CI, 0.72-0.99) compared with propensity-score matched controls. No significant associations were shown for incident heart failure (0.93; 95% CI, 0.84-1.04). The beneficial association of exercise-based CR on all-cause mortality was independent of sex, older age, comorbidities, and AF subtype. Conclusions Exercise-based CR among patients with incident AF was associated with lower odds of all-cause mortality, rehospitalization, and incident stroke at 18-month follow-up, supporting the provision of exercise-based CR for patients with AF.
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http://dx.doi.org/10.1161/JAHA.121.020804DOI Listing
June 2021

Challenges and opportunities in improving the management of atrial fibrillation: recent research advances and their clinical translation.

Cardiovasc Res 2021 Jun;117(7):1609-1611

Department of Medicine and Research Center, Montreal Heart Institute and Université de Montréal, 3655 Promenade Sir William Osler, Montreal QC, H3G 1Y6, Canada.

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http://dx.doi.org/10.1093/cvr/cvab170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208734PMC
June 2021

Chronic Kidney Disease and Cerebrovascular Disease: Consensus and Guidance From a KDIGO Controversies Conference.

Stroke 2021 Jun 3:STROKEAHA120029680. Epub 2021 Jun 3.

Ottawa Hospital Research Institute, Department of Medicine, The Ottawa Hospital, Civic Campus, ON, Canada (M.M.S.).

The global health burden of chronic kidney disease is rapidly rising, and chronic kidney disease is an important risk factor for cerebrovascular disease. Proposed underlying mechanisms for this relationship include shared traditional risk factors such as hypertension and diabetes, uremia-related nontraditional risk factors, such as oxidative stress and abnormal calcium-phosphorus metabolism, and dialysis-specific factors such as cerebral hypoperfusion and changes in cardiac structure. Chronic kidney disease frequently complicates routine stroke risk prediction, diagnosis, management, and prevention. It is also associated with worse stroke severity, outcomes and a high burden of silent cerebrovascular disease, and vascular cognitive impairment. Here, we present a summary of the epidemiology, pathophysiology, diagnosis, and treatment of cerebrovascular disease in chronic kidney disease from the Kidney Disease: Improving Global Outcomes Controversies Conference on central and peripheral arterial disease with a focus on knowledge gaps, areas of controversy, and priorities for research.
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http://dx.doi.org/10.1161/STROKEAHA.120.029680DOI Listing
June 2021

Predicting Silent Atrial Fibrillation in the Elderly: A Report from the NOMED-AF Cross-Sectional Study.

J Clin Med 2021 May 26;10(11). Epub 2021 May 26.

Department of Cardiology, Silesian Centre of Heart Diseases, 41-800 Zabrze, Poland.

Background: Silent atrial fibrillation (SAF) is common and is associated with poor outcomes.

Aims: to study the risk factors for AF and SAF in the elderly (≥65 years) general population and to develop a risk stratification model for predicting SAF.

Methods: Continuous ECG monitoring was performed for up to 30 days using a vest-based system in a cohort from NOMED-AF, a cross-sectional study based on a nationwide population sample. The independent risk factors for AF and SAF were determined using multiple logistic regression. ROC analysis was applied to validate the developed risk stratification score.

Results: From the total cohort of 3014 subjects, AF was diagnosed in 680 individuals (mean age, 77.5 ± 7.9; 50.1% men) with AF, and, of these, 41% had SAF. Independent associations with an increased risk of AF were age, male gender, coronary heart disease, thyroid diseases, prior ischemic stroke or transient ischemic attack (ICS/TIA), diabetes, heart failure, chronic kidney disease (CKD), obesity, and NT-proBNP >125 ng/mL. The risk factors for SAF were age, male gender, ICS/TIA, diabetes, heart failure, CKD, and NT-proBNP >125 ng/mL. We developed a clinical risk scale (MR-DASH score) that achieved a good level of prediction in the derivation cohort (AUC 0.726) and the validation cohort (AUC 0.730).

Conclusions: SAF is associated with various clinical risk factors in a population sample of individuals ≥65 years. Stratifying individuals from the general population according to their risk for SAF may be possible using the MR-DASH score, facilitating targeted screening programs of individuals with a high risk of SAF.
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http://dx.doi.org/10.3390/jcm10112321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199269PMC
May 2021

Smoking Cessation after Diagnosis of New-Onset Atrial Fibrillation and the Risk of Stroke and Death.

J Clin Med 2021 May 21;10(11). Epub 2021 May 21.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea.

Limited data are available regarding the impact of smoking cessation after atrial fibrillation (AF) diagnosis on clinical outcomes. Using the Korean National Health Insurance Service database, we included patients newly diagnosed with AF and categorized them into four groups as follows: (i) never smokers, (ii) ex-smokers, (iii) smoking cessation after AF diagnosis ("quitters"), and (iv) current smokers. The primary outcomes were incident ischemic stroke and all-cause death during follow-up. Fatal ischemic stroke and death from cerebrovascular events were evaluated as secondary outcomes. Among 97,637 patients (mean age, 61 years; mean CHADS-VASc score, 2.3), 6.9% stopped smoking after AF diagnosis. The mean follow-up duration was 3.2 ± 2.0 years. After multivariable adjustment, quitters had lower risks of ischemic stroke (hazard ratio (HR), 0.702; 95% confidence interval (CI), 0.595-0.827) and all-cause death (HR, 0.842; 95% CI, 0.748-0.948) than current smokers. Quitters after AF diagnosis were associated with lower risks of fatal ischemic stroke (HR, 0.454; 95% CI, 0.287-0.718) and death from cerebrovascular events (HR, 0.664; 95% CI, 0.465-0.949) compared with current smokers. Quitting smoking may reduce the risk of ischemic stroke, the severity of ischemic stroke, and the incidence of cerebrovascular events in patients with new-onset AF.
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http://dx.doi.org/10.3390/jcm10112238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196704PMC
May 2021

Hypertension and atrial fibrillation: Closing a virtuous circle.

PLoS Med 2021 Jun 1;18(6):e1003598. Epub 2021 Jun 1.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom.

Ying Gue and Gregory Lip discuss the accompanying study by Ana-Catarina Pinho-Gomes and co-workers on blood pressure lowering treatment in patients with atrial fibrillation.
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http://dx.doi.org/10.1371/journal.pmed.1003598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168876PMC
June 2021

Cryoablation as Initial Therapy for Atrial Fibrillation.

N Engl J Med 2021 05;384(21):e82

University of Liverpool, Liverpool, United Kingdom.

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http://dx.doi.org/10.1056/NEJMc2103408DOI Listing
May 2021

The effect of sex on the efficacy and safety of dual antithrombotic therapy with dabigatran versus triple therapy with warfarin after PCI in patients with atrial fibrillation (a RE-DUAL PCI subgroup analysis and comparison to other dual antithrombotic therapy trials).

Clin Cardiol 2021 May 27. Epub 2021 May 27.

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Background: The RE-DUAL PCI trial demonstrated that in patients with nonvalvular atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), dual therapy with dabigatran and a P2Y inhibitor, either clopidogrel or ticagrelor, reduced the risk of bleeding without an increased risk of thromboembolic events as compared to triple therapy with warfarin in addition to a P2Y inhibitor and aspirin. What remains unclear is whether this effect is consistent between males and females undergoing PCI.

Hypothesis: The reduction in risk of bleeding without increased risk of thromboembolic events with dual therapy with dabigatran and a P2Y inhibitor in comparison to triple therapy with warfarin, a P2Y inhibitor and aspirin is consistent in females and males.

Methods: The primary safety endpoint was the first International Society on Thrombosis and Hemostasis (ISTH) major bleeding event (MBE) or clinically relevant non-major bleeding event (CRNMBE). The efficacy endpoint was the composite of death, thromboembolic event (stroke, myocardial infarction, and systemic embolism) or unplanned revascularization. Cox proportional hazard regression analyses were applied to calculate corresponding hazard ratios and interaction p values for each endpoint.

Results: A total of 655 women and 2070 men were enrolled. The risk of major or CRNM bleeding was lower with both dabigatran 110 mg dual therapy and dabigatran 150 mg dual therapy compared with warfarin triple therapy in female and male patients (for 110 mg: females: HR 0.69, 95% CI 0.47-1.01, males: HR 0.46, 95% CI 0.37-0.59, interaction p value: 0.084 and for 150 mg: females HR 0.74, 95% CI 0.48-1.16, males HR 0.71, 95% CI 0.56-0.90, interaction p value: 0.83). There was also no detectable difference in the composite efficacy endpoint of death, thromboembolic events or unplanned revascularization between dabigatran dual therapy and warfarin triple therapy, with no statistically significant interaction between sex and treatment (interaction p values: 0.73 and 0.72, respectively).

Conclusions: Consistent with the overall study results, the risk of bleeding was lower with dabigatran 110 mg and 150 mg dual therapy compared with warfarin triple therapy, and risk of thromboembolic events was comparable with warfarin triple therapy independent of the patient's sex.
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http://dx.doi.org/10.1002/clc.23649DOI Listing
May 2021

Incident atrial fibrillation and its risk prediction in patients developing COVID-19: A machine learning based algorithm approach.

Eur J Intern Med 2021 May 14. Epub 2021 May 14.

Anthem Inc., Indianapolis, IN, USA.

Background: The elderly multi-morbid patient is at high risk of adverse outcomes with COVID-19 complications, and in the general population, the development of incident AF is associated with worse outcomes in such patients. There is therefore the need to identify those patients with COVID-19 who are at highest risk of developing incident AF. We therefore investigated incident AF risks in a large prospective population of elderly patients with/without incident COVID-19 cases and baseline cardiovascular/non-cardiovascular multi-morbidities. We used two approaches: main effect modeling and secondly, a machine-learning (ML) approach, accounting for the complex dynamic relationships among comorbidity variables.

Methods: We studied a prospective elderly US cohort of 280,592 patients from medical databases in an 8-month investigation of with/without newly incident COVID19 cases. Incident AF outcomes were examined in relationship to diverse multi-morbid conditions, COVID-19 status and demographic variables, with ML accounting for the dynamic nature of changing multimorbidity risk factors.

Results: Multi-morbidity contributed to the onset of confirmed COVID-19 cases with cognitive impairment (OR 1.69; 95%CI 1.52-1.88), anemia (OR 1.41; 95%CI 1.32-1.50), diabetes mellitus (OR 1.35; 95%CI 1.27-1.44) and vascular disease (OR 1.30; 95%CI 1.21-1.39) having the highest associations. A main effect model (C-index value 0.718) showed that COVID-19 had the highest association with incident AF cases (OR 3.12; 95%CI 2.61-3.710, followed by congestive heart failure (1.72; 95%CI 1.50-1.96), then coronary artery disease (OR 1.43; 95%CI 1.27-1.60) and valvular disease (1.42; 95%CI 1.26-1.60). The ML algorithm demonstrated improved discriminatory validity incrementally over the statistical main effect model (training: C-index 0.729, 95%CI 0.718-0.740; validation: C-index 0.704, 95%CI 0.687-0.72). Calibration of the ML based formulation was satisfactory and better than the main-effect model. Decision curve analysis demonstrated that the clinical utility for the ML based formulation was better than the 'treat all' strategy and the main effect model.

Conclusion: COVID-19 status has major implications for incident AF in a cohort with diverse cardiovascular/non-cardiovascular multi-morbidities. Our ML approach accounting for dynamic multimorbidity changes had good prediction for new onset AF amongst incident COVID19 cases.
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http://dx.doi.org/10.1016/j.ejim.2021.04.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118660PMC
May 2021

Adherence to the 'Atrial Fibrillation Better Care' Pathway in Patients with Atrial Fibrillation: Impact on Clinical Outcomes-A Systematic Review and Meta-Analysis of 285,000 Patients.

Thromb Haemost 2021 May 21. Epub 2021 May 21.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom.

Objective:  The 'Atrial fibrillation Better Care' (ABC) pathway has been recently proposed as a holistic approach for the comprehensive management of patients with atrial fibrillation (AF). We performed a systematic review of current evidence for the use of the ABC pathway on clinical outcomes.

Methods And Results:  We performed a systematic review and meta-analysis according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed and EMBASE were searched for studies reporting the prevalence of ABC-pathway-adherent management in AF patients, and its impact on clinical outcomes (all-cause death, cardiovascular death, stroke, and major bleeding). Meta-analysis of odds ratio (OR) was performed with random-effects models; subgroup analysis and meta-regression were performed to account for heterogeneity. Among the eight studies included, we found a pooled prevalence of ABC-adherent management of 21% (95% confidence interval, CI: 13-34%), with a high grade of heterogeneity, explained by the increasing adherence to each ABC criterion. Patients treated according to the ABC pathway showed a lower risk of all-cause death (OR: 0.42; 95% CI: 0.31-0.56), cardiovascular death (OR: 0.37; 95% CI: 0.23-0.58), stroke (OR: 0.55; 95% CI: 0.37-0.82) and major bleeding (OR: 0.69; 95% CI: 0.51-0.94), with moderate heterogeneity. Prevalence of comorbidities was moderators of heterogeneity for all-cause and cardiovascular death, while longer follow-up was associated with increased effectiveness for all outcomes.

Conclusion:  Adherence to the ABC pathway was suboptimal, being adopted in one in every five patients. Adherence to the ABC pathway was associated with a reduction in the risk of major adverse outcomes.
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http://dx.doi.org/10.1055/a-1515-9630DOI Listing
May 2021

Ferritinophagy and ferroptosis in the management of metabolic diseases.

Trends Endocrinol Metab 2021 Jul 15;32(7):444-462. Epub 2021 May 15.

Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Fudan University, Shanghai 200032, China; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA. Electronic address:

Ferroptosis is a form of regulated cell death modality associated with disturbed iron-homeostasis and unrestricted lipid peroxidation. Ample evidence has depicted an essential role for ferroptosis as either the cause or consequence for human diseases, denoting the likely therapeutic promises for targeting ferroptosis in the preservation of human health. Ferritinophagy, a selective form of autophagy, contributes to the initiation of ferroptosis through degradation of ferritin, which triggers labile iron overload (IO), lipid peroxidation, membrane damage, and cell death. In this review, we will delineate the role of ferritinophagy in ferroptosis, and its underlying regulatory mechanisms, to unveil the therapeutic value of ferritinophagy as a target in the combat of ferroptosis to manage metabolic diseases.
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http://dx.doi.org/10.1016/j.tem.2021.04.010DOI Listing
July 2021

Improving dynamic stroke risk prediction in non-anticoagulated patients with and without atrial fibrillation: Comparing common clinical risk scores and machine learning algorithms.

Eur Heart J Qual Care Clin Outcomes 2021 May 17. Epub 2021 May 17.

IngenioRX, Indianapolis, IN, USA.

Background: Diversified cardiovascular/non-cardiovascular multimorbid risk and efficient machine learning algorithms may facilitate improvements in stroke risk prediction, especially in newly diagnosed non-anticoagulated atrial fibrillation (AF) patients where initial decision-making on stroke prevention is needed.

Objective: sTo update common clinical risk assessment for stroke risk prediction in AF/non-AF cohorts with cardiovascular/non-cardiovascular multimorbid conditions; second, to improve stroke risk prediction using machine learning approaches; and third, to compare the improved clinical prediction rules for multi-morbid conditions using machine learning algorithms.

Data Design: We used cohort data from two health plans with 6,457,412 males/females contributing 14,188,679 person-years of data.

Predictive Modeling: The model inputs consisted of diversified list of comorbidities/demographic/temporal exposure variables, with the outcome capturing stroke event incidences. Machine learning algorithms used two parametric and two non-parametric techniques.

Results: The best prediction model was derived on the basis of non-linear formulations using machine learning criteria, with the highest c-index was obtained for logistic regression (0.892; 95%CI 0.886-0.898), with consistency on external validation (0.891; 95%CI 0.882-0.9). These were significantly higher than those based on the conventional stroke risk scores (CHADS2: 0.7488, 95% CI 0.746-0.7516; CHA2DS2-VASc: 0.7801, 95% CI 0.7772-0.7831) and multimorbid index (0.8508, 95% CI 0.8483-0.8532). The machine learning algorithm had good internal and external calibration, and net benefit values.

Conclusion: In this large cohort of newly diagnosed non-anticoagulated AF/non-AF patients, large improvements in stroke risk prediction can be shown with a cardiovascular/non-cardiovascular multimorbid index and a machine learning approach incorporating changes in risk related to ageing and incident comorbidities.
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http://dx.doi.org/10.1093/ehjqcco/qcab037DOI Listing
May 2021

Comparative effectiveness and safety of direct acting oral anticoagulants in nonvalvular atrial fibrillation for stroke prevention: a systematic review and meta-analysis.

Eur J Epidemiol 2021 May 15. Epub 2021 May 15.

Liverpool Centre for Cardiovascular Science, University of Liverpool, 6 West Derby St, Liverpool, L7 8TX, UK.

Purpose: To systematically review available evidence of indirect comparisons from RCTs and direct comparisons from observational studies regarding the comparative effectiveness and safety of DOACs in patients with AF.

Methods: Electronic databases including EMBASE, MEDLINE, and PUBMED were searched up to June 5th, 2020. Primary endpoints included effectiveness (stroke or systemic embolism [SE]) and safety (major bleeding) outcomes. Bucher methods and random-effects models were conducted for indirect and direct comparisons among DOACs, respectively. Ranking probability analyses and the number needed to treat for net effect (NNTnet) were applied.

Results: A total of 36 studies, involving 7 RCTs (n = 60,292 patients) and 29 observational studies (n = 1,164,821 patients), were included for analyses. Regarding the risk of stroke/SE, no significant differences were found from indirect comparisons of RCTs among the DOACs. For major bleeding, apixaban tended to be safer than rivaroxaban and dabigatran based on both direct and indirect comparisons (all p < 0.05; evidence quality: very low to moderate). Ranking probability analysis showed that apixaban had a high probability of being the best treatment in decreased risk of stroke/SE and major bleeding (80.30% and 91.30%, respectively). Likewise, apixaban was found to have the highest net clinical benefit (0.02, 95% CI: 0.014-0.029) and smallest NNTnet (48, 95% CI: 35-74).

Conclusions: Apixaban appeared to have a favorable effectiveness-safety profile compared with the other DOACs in AF for stroke prevention, based on evidence from both direct and indirect comparisons. However, additional high-quality evidence is needed to support firm recommendations on clinical decision-making.
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http://dx.doi.org/10.1007/s10654-021-00751-7DOI Listing
May 2021

Associations of Hepatosteatosis with Cardiovascular Disease in HIV Positive and HIV Negative Patients: The Liverpool HIV-Heart Project.

J Acquir Immune Defic Syndr 2021 May 8. Epub 2021 May 8.

Department of Cardiology, Royal Liverpool University Hospital, Liverpool UK Institute of Translational Medicine, University of Liverpool, Liverpool, UK Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool UK School of Computer Science and Mathematics, Liverpool John Moores University, Liverpool UK.

Background: Hepatosteatosis (HS) has been associated with cardiovascular disorders in the general population. We sought to investigate whether HS is a marker of CVD risk in HIV-positive individuals given that metabolic syndrome is implicated in the increasing CVD burden in this population.

Aims: To investigate the association of hepatosteatosis (HS) with cardiovascular disease (CVD) in HIV-positive and HIV-negative individuals.

Methods And Results: We analysed computed tomography (CT) images of 1304 subjects of whom 209 (16%) were HIV-positive and 1097 (84%) HIV-negative. CVD was quantified by the presence of coronary calcification from both cardiac-dedicated, and non-dedicated CT of the thorax. HS was diagnosed from CT datasets in those with non-contrast dedicated cardiac CT and those with venous phase CT of the liver using previously validated techniques. Prior liver ultrasound was also assessed for the presence of HS.The HIV-positive group had lower mean age (p<0.005), higher proportions of male sex (p<0.005) and more current smokers (p<0.005). The HIV-negative group had higher proportions of hypertension (p<0.005), type II diabetes (p=0.032), dyslipidaemia (p<0.005), statin use (p=0.008) and hepatosteatosis (HS) (p=0.018). The prevalence of coronary calcification was not significantly different between the groups.Logistic regression demonstrated that in the HIV-positive group, increasing age (OR: 1.15, p<0.005), male sex (OR 3.37, p=0.022) and HS (p=0.005) were independently associated with CVD. In the HIV-negative group, increasing age (OR: 1.11, p<0.005), male sex (p<0.005), current smoking (p<0.005) and dyslipidaemia (p=0.03) were independently associated with CVD. Using a machine learning random forest algorithm to assess the variables of importance, the top three variables of importance in the HIV-positive group were age, HS and male sex. In the HIV-negative group the top three variables were: age, male sex and HS. The logistic regression models predicted CVD well, with the mean area under the receiver operator curve (AUC) for the HIV-positive and HIV negative cohorts being 0.831 (95% CI: 0.713 - 0.928) and 0.786 (95% CI: 0.735 - 0.836), respectively. The random forest models outperformed logistic regression models, with a mean AUC in HIV-positive and HIV-negative populations of 0.877 (95% CI: 0.775-0.959) and 0.828 (95% CI: 0.780-0.873) respectively, with differences between both methods being statistically significant.

Conclusion: In contrast to the general population, HS is a strong and independent predictor of CVD in HIV-positive individuals. This suggests that metabolic dysfunction may be attributable to the excess CVD risk seen with these patient groups. Assessment of HS may help accurate quantification of CVD risk in HIV-positive patients.
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http://dx.doi.org/10.1097/QAI.0000000000002721DOI Listing
May 2021

How machine learning is impacting research in atrial fibrillation: implications for risk prediction and future management.

Cardiovasc Res 2021 Jun;117(7):1700-1717

Liverpool Centre for Cardiovascular Science, Liverpool John Moores University, Liverpool, UK.

There has been an exponential growth of artificial intelligence (AI) and machine learning (ML) publications aimed at advancing our understanding of atrial fibrillation (AF), which has been mainly driven by the confluence of two factors: the advances in deep neural networks (DeepNNs) and the availability of large, open access databases. It is observed that most of the attention has centred on applying ML for dvsetecting AF, particularly using electrocardiograms (ECGs) as the main data modality. Nearly a third of them used DeepNNs to minimize or eliminate the need for transforming the ECGs to extract features prior to ML modelling; however, we did not observe a significant advantage in following this approach. We also found a fraction of studies using other data modalities, and others centred in aims, such as risk prediction, AF management, and others. From the clinical perspective, AI/ML can help expand the utility of AF detection and risk prediction, especially for patients with additional comorbidities. The use of AI/ML for detection and risk prediction into applications and smart mobile health (mHealth) technology would enable 'real time' dynamic assessments. AI/ML could also adapt to treatment changes over time, as well as incident risk factors. Incorporation of a dynamic AI/ML model into mHealth technology would facilitate 'real time' assessment of stroke risk, facilitating mitigation of modifiable risk factors (e.g. blood pressure control). Overall, this would lead to an improvement in clinical care for patients with AF.
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http://dx.doi.org/10.1093/cvr/cvab169DOI Listing
June 2021

Treatment timing and the effects of rhythm control strategy in patients with atrial fibrillation: nationwide cohort study.

BMJ 2021 05 11;373:n991. Epub 2021 May 11.

Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

Objective: To investigate whether the results of a rhythm control strategy differ according to the duration between diagnosis of atrial fibrillation and treatment initiation.

Design: Longitudinal observational cohort study.

Setting: Population based cohort from the Korean National Health Insurance Service database.

Participants: 22 635 adults with atrial fibrillation and cardiovascular conditions, newly treated with rhythm control (antiarrhythmic drugs or ablation) or rate control strategies between 28 July 2011 and 31 December 2015.

Main Outcome Measure: A composite outcome of death from cardiovascular causes, ischaemic stroke, admission to hospital for heart failure, or acute myocardial infarction.

Results: Of the study population, 12 200 (53.9%) were male, the median age was 70, and the median follow-up duration was 2.1 years. Among patients with early treatment for atrial fibrillation (initiated within one year since diagnosis), compared with rate control, rhythm control was associated with a lower risk of the primary composite outcome (weighted incidence rate per 100 person years 7.42 in rhythm control 9.25 in rate control; hazard ratio 0.81, 95% confidence interval 0.71 to 0.93; P=0.002). No difference in the risk of the primary composite outcome was found between rhythm and rate control (weighted incidence rate per 100 person years 8.67 in rhythm control 8.99 in rate control; 0.97, 0.78 to 1.20; P=0.76) in patients with late treatment for atrial fibrillation (initiated after one year since diagnosis). No significant differences in safety outcomes were found between the rhythm and rate control strategies across different treatment timings. Earlier initiation of treatment was linearly associated with more favourable cardiovascular outcomes for rhythm control compared with rate control.

Conclusions: Early initiation of rhythm control treatment was associated with a lower risk of adverse cardiovascular outcomes than rate control treatment in patients with recently diagnosed atrial fibrillation. This association was not found in patients who had had atrial fibrillation for more than one year.
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http://dx.doi.org/10.1136/bmj.n991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111568PMC
May 2021

Use of Non-Vitamin K Antagonist Oral Anticoagulants Among Patients with Nonvalvular Atrial Fibrillation and Multimorbidity.

Adv Ther 2021 06 7;38(6):3166-3184. Epub 2021 May 7.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK.

Introduction: Non-valvular atrial fibrillation (NVAF) is often accompanied by multiple comorbid conditions, which increase the associated risks and complexity of patient management. This study evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) among multimorbid patients with NVAF who were prescribed non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin.

Methods: A retrospective study of patients with NVAF and high multimorbidity who initiated apixaban, dabigatran, rivaroxaban, or warfarin from 1 January 2013 to 30 September 2015 was conducted using five insurance claims databases. Multimorbidity was defined as six or more comorbid conditions, and 1:1 propensity score matching (PSM) was conducted between the NOAC-warfarin and NOAC-NOAC cohorts. Cox proportional hazard models were used to evaluate the hazard ratios of stroke/SE and MB.

Results: Of the NVAF population (n = 466,991), 33.4% (n = 155,959) had multimorbidity, including 36,921 apixaban, 10,248 dabigatran, 45,509 rivaroxaban, and 63,281 warfarin patients. Compared to warfarin, apixaban and rivaroxaban were associated with a lower risk of stroke/SE (hazard ratio [HR] 0.63, 95% CI 0.54-0.74; HR 0.70, 95% CI 0.64-0.77, respectively). Apixaban and dabigatran were associated with a lower risk of MB (HR 0.61, 95% CI 0.56-0.67; HR 0.75, 95% CI 0.66-0.86, respectively) and rivaroxaban was associated with a higher risk of MB (HR 1.06, 95% CI 1.01-1.12) compared to warfarin.

Conclusions: Among patients with NVAF and six or more comorbid conditions, NOACs were associated with varying risk of stroke/SE and MB compared to warfarin and to each other. Rather than a "one drug fits all" approach, our results may be useful for appropriate OAC treatment for multimorbid patients.
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http://dx.doi.org/10.1007/s12325-021-01724-8DOI Listing
June 2021

Quality of care and risk of incident atrial fibrillation in patients with newly-diagnosed heart failure: A nationwide cohort study.

Eur Heart J Qual Care Clin Outcomes 2021 May 7. Epub 2021 May 7.

Danish Center for Clinical Health Services Research, Aalborg University, Aalborg, Denmark.

Aims: Incident atrial fibrillation (AF) is an adverse prognostic indicator in heart failure (HF); identifying modifiable targets may be relevant to reduce the incidence and morbidity of AF. Therefore, we examined the association between quality of HF care and risk of AF.

Methods And Results: Using the Danish Heart Failure Registry, we conducted a nationwide registry-based cohort study of all incident HF patients diagnosed between 2008 and 2018 and without history of AF. Quality of HF care was assessed by seven process performance measures, including echocardiographic examination, New York Heart Association classification, treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta-blockers, and mineralocorticoid antagonists, physical training, and patient education. In the main analysis, we examined adherence with all measures in a cohort of 25,100 patients (mean age 68.5 ± 13.2 years; 33.6% women). The median follow-up was 3.1 years. Cox proportional hazard regressions estimated the hazard ratios (HRs) with 95% confidence intervals (95% CIs) between the number of fulfilled measures and incident AF. In a multivariable-adjusted analysis with 0 fulfilled performance measures as reference, the HRs (95% CIs) were 1: 0.78 (0.61-1.00), 2: 0.63 (0.49-0.80), 3: 0.53 (0.36-0.80), 4: 0.64 (0.44-0.94), 5: 0.56 (0.39-0.82), 6: 0.51 (0.35-0.74), and 7: 0.49 (0.33-0.73), with a significant decreasing linear trend (p < 0.001).

Conclusion: In patients with incident HF, fulfillment of guideline-based process performance measures was associated with decreased long-term risk of AF. This study supports initiatives to improve the quality of care for patients with HF to prevent incident AF.
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http://dx.doi.org/10.1093/ehjqcco/qcab036DOI Listing
May 2021

The Reply.

Am J Med 2021 05;134(5):e354-e355

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address:

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http://dx.doi.org/10.1016/j.amjmed.2020.11.033DOI Listing
May 2021

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and cardiac arrhythmias: a systematic review and meta-analysis.

Cardiovasc Diabetol 2021 05 7;20(1):100. Epub 2021 May 7.

Division of Cardiology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Room 1929B/K1931, Block K, Hong Kong, China.

Background: Cardiac arrhythmias are associated with poorer outcomes in patients with heart failure (HF), diabetes mellitus (DM), and chronic kidney disease (CKD). Previous studies have shown inconsistent conclusions regarding the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the risk of developing arrhythmias. This study aims to investigate the association of SGLT2i treatment with arrhythmia outcomes in clinical trials of patients with HF, DM, or CKD.

Methods: MEDLINE, EMBASE, and ClinicalTrials.gov were searched from inception up to 27 August 2020. Randomized controlled trials that randomized patients with DM, CKD, or HF to SGLT2i or placebo were included. The outcomes of interest include atrial fibrillation (AF), embolic stroke, atrial flutter (AFL), AF/AFL, ventricular tachycardia (VT), and cardiac arrest. Relative risks (RRs) and 95% confidence intervals (CI) were pooled using a random-effects model.

Results: Out of 4,532 citations, 22 trials with altogether 52,115 patients were included (mean age 63.2 years; 33,747 [64.8%] of participants were men). SGLT2i were associated with a lower risk of AF (RR 0.82, 95% CI 0.70-0.96), embolic stroke (RR 0.32, 95% CI 0.12-0.85), AF/AFL (RR 0.82, 95% CI 0.71-0.95), and VT (RR 0.73, 95% CI 0.53-0.99), while the risk reductions in AFL (RR 0.83, 95% CI 0.58-1.17) and cardiac arrest (RR 0.83, 95% CI 0.61-1.14) did not reach statistical significance. The associations appeared to be consistent across different baseline conditions (DM vs CKD vs HF; atherosclerotic cardiovascular disease [ASCVD] vs no ASCVD) and the SGLT2i used.

Conclusions: SGLT2i reduced the risk of cardiac arrhythmias. Our study provides further evidence for recommending the use of SGLT2i in patients with DM, CKD, and HF. Further research is needed to fully elucidate the mechanism by which SGLT2i protect against arrhythmias.
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http://dx.doi.org/10.1186/s12933-021-01293-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106208PMC
May 2021