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Aims Despite landmark heart failure (HF) with reduced ejection fraction (HFrEF) trials showing effect of mineralocorticoid receptor antagonists (MRA) on the risk of death and HF hospitalization, it has been suggested that MRAs are underutilized or frequently withdrawn. This study sought to identify temporal trends in the initiation of MRAs and the subsequent risk of withdrawal and adherence of MRAs in HF patients treated with a renin-angiotensin system inhibitor and a beta-blocker in Denmark from 2003-2017. Methods and results From nationwide registries, we identified patients receiving a diagnosis of HF. Use of MRA was identified by at least one prescription within 6 months after the diagnosis. The absolute risk of withdrawal with treatment was assessed with cumulative incidence, accounting for the competing risk of death. To estimate adherence, we calculated the proportion of days covered. We included 51 512 patients with incident HF. During the study period, 20 779 (40.3%) patients initiated MRA therapy. The incidence of withdrawal of MRA was 49.2% throughout the study period; 48.0% of the HF patients were adherent to the treatment. Among patients withdrawing treatment with MRA, the cumulative incidence of reinitiating was 36.6%. Conclusions In a nationwide cohort of patients with HF, approximately half of the patients received MRA as third-line therapy within the first 6 months after diagnosis and approximately half of these withdrew MRA within 5 years. These findings warrant an increasing focus on retention to MRA treatment in a real-life setting. [ABSTRACT FROM AUTHOR]

Objective: Chronic heart failure with reduced ejection fraction (HF-REF) represents a major public health issue and is associated with considerable morbidity and mortality. We evaluated the cost-effectiveness of sacubitril/valsartan (formerly LCZ696) compared with an ACE inhibitor (ACEI) (enalapril) in the treatment of HF-REF from the perspective of healthcare providers in the UK, Denmark and Colombia.Methods: A cost-utility analysis was performed based on data from a multinational, Phase III randomised controlled trial. A decision-analytic model was developed based on a series of regression models, which extrapolated health-related quality of life, hospitalisation rates and survival over a lifetime horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER).Results: In the UK, the cost per quality-adjusted life-year (QALY) gained for sacubitril/valsartan (using cardiovascular mortality) was £17 100 (€20 400) versus enalapril. In Denmark, the ICER for sacubitril/valsartan was Kr 174 000 (€22 600). In Colombia, the ICER was COP$39.5 million (€11 200) per QALY gained. Deterministic sensitivity analysis showed that results were most sensitive to the extrapolation of mortality, duration of treatment effect and time horizon, but were robust to other structural changes, with most scenarios associated with ICERs below the willingness-to-pay threshold for all three country settings. Probabilistic sensitivity analysis suggested the probability that sacubitril/valsartan was cost-effective at conventional willingness-to-pay thresholds was 68%-94% in the UK, 84% in Denmark and 95% in Colombia.Conclusions: Our analysis suggests that, in all three countries, sacubitril/valsartan is likely to be cost-effective compared with an ACEI (the current standard of care) in patients with HF-REF. [ABSTRACT FROM AUTHOR]

Background: Febuxostat and allopurinol are urate-lowering therapies used to treat patients with gout. Following concerns about the cardiovascular safety of febuxostat, the European Medicines Agency recommended a post-licensing study assessing the cardiovascular safety of febuxostat compared with allopurinol.Methods: We did a prospective, randomised, open-label, blinded-endpoint, non-inferiority trial of febuxostat versus allopurinol in patients with gout in the UK, Denmark, and Sweden. Eligible patients were 60 years or older, already receiving allopurinol, and had at least one additional cardiovascular risk factor. Those who had myocardial infarction or stroke in the previous 6 months or who had severe congestive heart failure or severe renal impairment were excluded. After a lead-in phase in which allopurinol dose was optimised towards achieving a serum urate concentration of less than 0·357 mmol/L (<6 mg/dL), patients were randomly assigned (1:1, with stratification according to previous cardiovascular events) to continue allopurinol (at the optimised dose) or start febuxostat at 80 mg/day, increasing to 120 mg/day if necessary to achieve the target serum urate concentration. The primary outcome was a composite of hospitalisation for non-fatal myocardial infarction or biomarker-positive acute coronary syndrome; non-fatal stroke; or cardiovascular death. The hazard ratio (HR) for febuxostat versus allopurinol in a Cox proportional hazards model (adjusted for the stratification variable and country) was assessed for non-inferiority (HR limit 1·3) in an on-treatment analysis. This study is registered with the EU Clinical Trials Register (EudraCT 2011-001883-23) and ISRCTN (ISRCTN72443728) and is now closed.Findings: From Dec 20, 2011, to Jan 26, 2018, 6128 patients (mean age 71·0 years [SD 6·4], 5225 [85·3%] men, 903 [14·7%] women, 2046 [33·4%] with previous cardiovascular disease) were enrolled and randomly allocated to receive allopurinol (n=3065) or febuxostat (n=3063). By the study end date (Dec 31, 2019), 189 (6·2%) patients in the febuxostat group and 169 (5·5%) in the allopurinol group withdrew from all follow-up. Median follow-up time was 1467 days (IQR 1029-2052) and median on-treatment follow-up was 1324 days (IQR 870-1919). For incidence of the primary endpoint, on-treatment, febuxostat (172 patients [1·72 events per 100 patient-years]) was non-inferior to allopurinol (241 patients [2·05 events per 100 patient-years]; adjusted HR 0·85 [95% CI 0·70-1·03], p<0·0001). In the febuxostat group, 222 (7·2%) of 3063 patients died and 1720 (57·3%) of 3001 in the safety analysis set had at least one serious adverse event (with 23 events in 19 [0·6%] patients related to treatment). In the allopurinol group, 263 (8·6%) of 3065 patients died and 1812 (59·4%) of 3050 had one or more serious adverse events (with five events in five [0·2%] patients related to treatment). Randomised therapy was discontinued in 973 (32·4%) patients in the febuxostat group and 503 (16·5%) patients in the allopurinol group.Interpretation: Febuxostat is non-inferior to allopurinol therapy with respect to the primary cardiovascular endpoint, and its long-term use is not associated with an increased risk of death or serious adverse events compared with allopurinol.Funding: Menarini, Ipsen, and Teijin Pharma Ltd. [ABSTRACT FROM AUTHOR]

Background: Return to work is important financially, as a marker of functional status and for self-esteem in patients developing chronic illness. We examined return to work after first heart failure (HF) hospitalization.Methods: By individual-level linkage of nationwide Danish registries, we identified 21 455 patients of working age (18-60 years) with a first HF hospitalization in the period from 1997 to 2012. Of these patients, 11 880 (55%) were in the workforce before HF hospitalization and comprised the study population. We applied logistic regression to estimate odds ratios for associations between age, sex, length of hospital stay, level of education, income, comorbidity, and return to work.Results: One year after first HF hospitalization, 8040 (67.7%) returned to the workforce, 2981 (25.1%) did not, 805 (6.7%) died, and 54 (0.5%) emigrated. Predictors of return to work included younger age (18-30 versus 51-60 years; odds ratio [OR], 3.12; 95% confidence interval [CI], 2.42-4.03), male sex (OR, 1.22; 95% CI, 1.12-1.34), and level of education (long-higher versus basic school; OR, 2.06; 95% CI, 1.63-2.60). Conversely, hospital stay >7 days (OR, 0.56; 95% CI, 0.51-0.62) and comorbidity including history of stroke (OR, 0.55; 95% CI, 0.45-0.69), chronic kidney disease (OR, 0.46; 95% CI, 0.36-0.59), chronic obstructive pulmonary disease (OR, 0.62; 95% CI, 0.52-0.75), diabetes mellitus (OR 0.76; 95% CI, 0.68-0.85), and cancer (OR, 0.49; 95% CI, 0.40-0.61) were all significantly associated with lower chance of return to work.Conclusions: Patients in the workforce before HF hospitalization had low mortality but high risk of detachment from the workforce 1 year later. Young age, male sex, and a higher level of education were predictors of return to work. [ABSTRACT FROM AUTHOR]

Aims: Although recent randomized clinical trials have demonstrated the advantages of heart failure (HF) therapy in both frail and not frail patients, there is insufficient information on the use of HF therapy based on frailty status in a real-world setting. The aim was to examine how frailty status in HF patients associates with use of HF therapy and with clinical outcomes., Methods and Results: Patients with new-onset HF between 2014 and 2021 were identified using the nationwide Danish registers. Patients across the entire range of ejection fraction were included. The associations between frailty status (using the Hospital Frailty Risk Score) and use of HF therapy and clinical outcomes (all-cause mortality, HF hospitalization, and non-HF hospitalization) were evaluated using multivariable-adjusted Cox models adjusting for age, sex, diagnostic setting, calendar year, comorbidities, pharmacotherapy, and socioeconomic status. Of 35 999 participants (mean age 69.1 years), 68% were not frail, 26% were moderately frail, and 6% were severely frail. The use of HF therapy was significantly lower in frailer patients. The hazard ratio (HR) for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker initiation was 0.74 (95% confidence interval 0.70-0.77) and 0.48 (0.43-0.53) for moderate frailty and severe frailty, respectively. For beta-blockers, the corresponding HRs were 0.74 (0.71-0.78) and 0.51 (0.46-0.56), respectively, and for mineralocorticoid receptor antagonists, 0.83 (0.80-0.87) and 0.58 (0.53-0.64), respectively. The prevalence of death and non-HF hospitalization increased with frailty status. The HR for death was 1.55 (1.47-1.63) and 2.32 (2.16-2.49) for moderate and severe frailty, respectively, and the HR for non-HF hospitalization was 1.37 (1.32-1.41) and 1.82 (1.72-1.92), respectively. The association between frailty status and HF hospitalization was not significant (HR 1.08 [1.02-1.14] and 1.08 [0.97-1.20], respectively)., Conclusion: In real-world HF patients, frailty was associated with lower HF therapy use and with a higher incidence of clinical outcomes including mortality and non-HF hospitalization., (© 2024 European Society of Cardiology.)

Background: Despite advances in heart failure care reducing mortality in clinical trials, it remains unclear whether real-life cohorts have had similar improvements in life expectancy across the age spectrum. We aimed to investigate how mortality trends changed in patients with heart failure over the past 25 years, stratified by age groups., Methods: Using Danish nationwide registries, we identified patients with new-onset heart failure aged 18-95 years. The 5-year all-cause mortality risk and the absolute risk difference of mortality between patients with heart failure and age-matched and sex-matched heart failure-free controls were assessed using Kaplan-Meier estimates and multivariable Cox regression models. Mortality trends were analysed across five calendar periods (1996-2000, 2001-05, 2006-10, 2011-15, and 2016-20) and three age groups (<65 years, 65-79 years, and ≥80 years)., Findings: 194 997 patients with heart failure were included. Mortality significantly decreased from 1996-2000 (66% [95% CI 65·5-66·4]) to 2016-20 (43% [42·1-43·4]), with similar results shown in all age groups (<65 years: 35% [33·9-36·1] to 15% [14·6-16·3]; 65-79 years: 64% [63·1-64·5] to 39% [37·6-39·6]; and ≥80 years: 84% [83·1-84·3] to 73% [71·7-73·9]). Adjusted mortality rates supported these associations. The absolute risk difference declined notably in younger age groups (<65 years: 29·9% [28·8-31·0] to 12·7% [12·0-13·4] and 65-79 years: 41·1% [40·3-41·9] to 25·1% [24·4-25·8]), remaining relatively stable in those aged 80 years or older (30·6% [29·9-31·3] to 28% [27·2-28·8])., Interpretation: Over 25 years, there has been a consistent decrease in mortality among patients with heart failure across age groups, albeit less prominently in patients aged 80 years or older. Further insight is needed to identify effective strategies for improving disease burden in older patients with heart failure., Funding: None., Translation: For the Danish translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests MS reports lecture fees from Boehringer, Novo AstraZeneca, and Novartis. MCP reports grants from Boehringer Ingelheim, Roche, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, and Pharmacosmos, and lecture and consultant fees from Akero, Applied Therapeutics, Amgen, AnaCardio, Biosensors, Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Horizon Therapeutics, Takeda, Cardiorentis, Pharmacosmos, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, Teikoku, LIB Therapeutics, and 3R Lifesciences. JJVM reports lecture fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharmaceuticals, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J B Chemicals & Pharmaceuticals, Lupin Pharmaceuticals, Medscape/Heart. Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, and Translational Medicine Academy, and consultant fees from Akero, Applied Therapeutics, Amgen, AnaCardio, Biosensors, Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Horizon Therapeutics, Takeda, Cardiorentis, Pharmacosmos, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, Teikoku, LIB Therapeutics, and 3R Lifesciences. LK reports speaker's honorarium from AstraZeneca, Bayer, Boehringer, Novartis and Novo. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Whether frailty influences the initiation of two cardioprotective diabetes drug therapies (ie, SGLT2 inhibitors and GLP-1 receptor agonists) in people with type 2 diabetes and cardiovascular disease is unknown. We aimed to assess rates of initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to frailty in people with type 2 diabetes and cardiovascular disease., Methods: For this cross-sectional, nationwide study, all people with type 2 diabetes and cardiovascular disease in Denmark between Jan 1, 2015, and Dec 31, 2021, from six Danish health-data registers were identified. People younger than 40 years, with end-stage renal disease, with registered contraindications to SGLT2 inhibitors or GLP-1 receptor agonists, or with previous use of either drug therapy were excluded. The Hospital Frailty Risk Score was used to categorise people as either non-frail, moderately frail, or severely frail. Cox proportional hazards models were used to analyse the association between frailty and initiation of an SGLT2 inhibitor or a GLP-1 receptor agonist., Findings: Of 119 390 people with type 2 diabetes and cardiovascular disease, 103 790 were included. Median follow-up time was 4·5 years (IQR 2·7-6·1) and median age across the three frailty groups was 71 years (64-79). 65 959 (63·6%) of 103 790 people were male and 37 831 (36·5%) were female. At index date, 66 910 (64·5%) people were non-frail, 29 250 (28·2%) were moderately frail, and 7630 (7·4%) were severely frail. Frailty was associated with a significantly lower probability of initiating therapy with an SGLT2 inhibitor or a GLP-1 receptor agonist than in people who were non-frail (moderately frail hazard ratio 0·91, 95% CI 0·88-0·94, p<0·0001; severely frail 0·75, 0·70-0·80, p<0·0001). This association persisted after adjustment for age, sex, socioeconomic status, year of inclusion, duration of type 2 diabetes, duration of cardiovascular disease, polypharmacy, and comorbidity., Interpretation: In people with type 2 diabetes and cardiovascular disease in Denmark, frailty was associated with a significantly lower probability of SGLT2-inhibitor or GLP-1 receptor-agonist initiation, despite their benefits. Formulating clear and updated guidelines on the use of SGLT2 inhibitors and GLP-1 receptor agonists in people who are frail with type 2 diabetes and cardiovascular disease should be a priority., Funding: Department of Cardiology, Herlev and Gentofte University Hospital., Translation: For the Danish translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests MEM receives grants from the CARDIO-HGH Foundation, Herlev and Gentofte University Hospital, and the Danish Cardiovascular Academy. MS receives lecture fees from Novartis, Boehringer Ingelheim, AstraZeneca, and Novo Nordisk. ACF receives grants from Steno Diabetes Center Sjaelland, Region Sjælland Den Sundhedsvidenskabelige Forskningsfond, and Murermester Lauritz Peter Christensen og Hustru Kirsten Sigrid Christensens Fond. JHB participates on an advisory board for Bayer. JJ receives grants from The Danish Heart Foundation and the CARDIO-HGH Foundation; receives payment and honoraria for lectures, presentations, and manuscript writing from Boehringer Ingelheim; and participates on advisory boards for AstraZeneca and Boehringer Ingelheim. JES receives grants from Herlev-Gentofte Forskningsfond, Snedkermester Sophus Jacobs; Torben og Alice Frimodts Fond; Dagmar Marshalls Fond; and Eva og Henry Frænkels Mindefond. LK receives speaker honoraria from Novo Nordisk, AstraZeneca, Novartis, and Boehringer Ingelheim. MCP receives grants and contracts from Boehringer Ingelheim, Roche, SQ Innovation, AstraZeneca, Novartis, Novo Nordisk, and Pharmacosmos; receives consulting fees from Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Takeda, Corvia, Cardiorentis, Pharmacosmos, Siemens, and Vifor; receives payment or honoraria for lectures, presentations, manuscript writing, or educational events from Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Takeda, Corvia, Cardiorentis, Pharmacosmos, Siemens, and Vifor; participates on a data safety monitoring board and advisory board for Takeda and Taikoku; and is the Director of Global Clinical Trials Partners. NS receives grants and contracts from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics; receives consulting fees from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi; and receives fees for lectures or manuscript writing from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, and Novo Nordisk. JJVM receives payment or honoraria for lectures, presentations, speaker bureaus, or manuscript writing from Abbott, Alkem Metabolics, Eris Lifesciences, Hikma, Lupin, Sun Pharmaceuticals, Medscape, Herat.org, ProAdWise, Servier, and the Corpus. JJVM receives payment for participating on advisory boards for Cytokinetics, Amgen, AstraZeneca, Theracos, Ionis Pharmaceuticals, DalCor, Cardurion, Novartis, GlaxoSmithKline, Bayer, KBP Biosciences, Boehringer Ingelheim, and Bristol Myers Squibb. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background Guideline-recommended disease-modifying pharmacological therapies for heart failure (HF) with reduced ejection fraction are underutilized, particularly among elderly patients. We studied the association of age in adherence and discontinuation of angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers (ACEi/ARB), β-blockers (BB), and mineralocorticoid receptor antagonists. Methods and Results Patients with a first heart failure diagnosis who had initiated ACEi/ARB and BB within 120 days of presentation were included from nationwide registries and divided into 3 age groups: <65 years (reference), 65 to 79, and ≥80. One-year median proportions of daily target doses were calculated. Adherence was estimated by the proportion of days covered. The 5-year risk of discontinuation was assessed with the Aalen-Johansen estimator. Discontinuation rates were evaluated using Multivariable Cox regression. Twenty-nine thousand four hundred eighty-two patients were included. Advancing age was associated with lower median proportions of daily target doses and adherence (ACEi/ARB 79.1%, 77.5%, and 69.4%; BB 79.1%, 78.6%, and 73.8%), in the <65, 65 to 79, and ≥80 age groups, respectively. Age ≥80 was associated with higher discontinuation rates (cumulative incidence, ACEi/ARB 41%, 44%, and 51%; BB 38%, 35%, and 39%; hazard ratio, ACEi/ARB 1.60 [95% CI, 1.51-1.69]; BB 1.33 [95% CI, 1.25-1.41]). The risk of mineralocorticoid receptor antagonists discontinuation differed little with age (50%, 54%, and 56%), although mineralocorticoid receptor antagonists initiation in the most elderly was less frequent (33%, 33%, and 22%). Conclusions In a nationwide cohort of patients with heart failure, advanced age was associated with lower proportions of daily target doses, lower adherence, and higher discontinuation rates of ACEi/ARB and BBs. Focus on treatment adherence and optimal dosages among elderly patients with heart failure could improve outcomes.

Background: Patients with chronic diseases are at higher risk of requiring domiciliary and nursing home care, but how different chronic diseases compare in terms of risk is not known. We examined initiation of domiciliary care and nursing home admission among patients with heart failure (HF), stroke, COPD and cancer., Methods: Patients with a first-time hospitalization for HF, stroke, COPD or cancer from 2008-2016 were identified. Patients were matched on age and sex and followed for five years., Results: 111,144 patients, 27,786 with each disease, were identified. The median age was 69 years and two thirds of the patients were men. The 5-year risk of receiving domiciliary care was; HF 20.9%, stroke 25.2%, COPD 24.6% and cancer 19.3%. The corresponding adjusted hazard ratios (HRs), with HF patients used as reference, were: stroke 1.35[1.30-1.40]; COPD 1.29[1.25-1.34]; and cancer 1.19[1.14-1.23]. The five-year incidence of nursing home admission was 6.6% for stroke, and substantially lower in patients with HF(2.6%), COPD(2.6%) and cancer (1.5%). The adjusted HRs were (HF reference): stroke, 2.44 [2.23-2.68]; COPD 1.01 [0.91-1.13] and cancer 0.76 [0.67-0.86]. Living alone, older age, diabetes, chronic kidney disease, depression and dementia predicted a higher likelihood of both types of care., Conclusions: In patients with HF, stroke, COPD or cancer 5-year risk of domiciliary care and nursing home admission, ranged from 19-25% and 1-7%, respectively. Patients with stroke had the highest rate of domiciliary care and were more than twice as likely to be admitted to a nursing home, compared to patients with the other conditions., Competing Interests: The authors have declared that no competing interests exist.

Background: Data on long-term cardiovascular outcomes in systemic lupus erythematosus (SLE) are sparse., Objectives: This study sought to examine the long-term risk and prognosis associated with cardiovascular outcomes, including heart failure (HF), in patients with SLE., Methods: Using Danish administrative registries, risks of outcomes were compared between SLE patients (diagnosed 1996 to 2018, no history of cardiovascular disease) and age-, sex-, and comorbidity-matched control subjects from the background population (matched 1:4). Furthermore, mortality following HF diagnosis was compared between SLE patients developing HF and age- and sex-matched non-SLE control subjects with HF (matched 1:4)., Results: A total of 3,411 SLE patients (median age: 44.6 years [25th to 75th percentile: 31.9 to 57.0 years]; 14.1% men) were matched with 13,644 control subjects. The median follow-up was 8.5 years (25th to 75th percentile: 4.0 to 14.4 years). Absolute 10-year risks of outcomes were: HF, 3.71% (95% confidence interval [CI]: 3.02% to 4.51%) for SLE patients, 1.94% (95% CI: 1.68% to 2.24%) for control subjects; atrial fibrillation, 4.35% (95% CI: 3.61% to 5.18%) for SLE patients, 2.82% (95% CI: 2.50% to 3.16%) for control subjects; ischemic stroke, 3.75% (95% CI: 3.06% to 4.54%) for SLE patients, 1.92% (95% CI: 1.66% to 2.20%) for control subjects; myocardial infarction, 2.17% (95% CI: 1.66% to 2.80%) for SLE patients, 1.49% (95% CI: 1.26% to 1.75%) for control subjects; venous thromboembolism, 6.03% (95% CI: 5.17% to 6.98%) for SLE patients, 1.68% (95% CI: 1.44% to 1.95%) for control subjects; and the composite of implantable cardioverter-defibrillator implantation/ventricular arrhythmias/cardiac arrest, 0.89% (95% CI: 0.58% to 1.31%) for SLE patients, 0.30% (95% CI: 0.20% to 0.43%) for control subjects. SLE with subsequent HF was associated with higher mortality compared with HF without SLE (adjusted hazard ratio: 1.50; 95% CI: 1.08 to 2.08)., Conclusions: SLE patients had a higher associated risk of HF and other cardiovascular outcomes compared with matched control subjects. Among patients developing HF, a history of SLE was associated with higher mortality., Competing Interests: Funding Support and Author Disclosures All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy) targeted young sarcomeric gene mutation carriers with early-stage hypertrophic cardiomyopathy (HCM) to test whether valsartan can modify disease progression. We describe the baseline characteristics of the VANISH cohort and compare to previous trials evaluating angiotensin receptor blockers., Methods: Applying a randomized, double-blinded, placebo-controlled design, 178 participants with nonobstructive HCM (age, 23.3±10.1 years; 61% men) were randomized in the primary cohort and 34 (age, 16.5±4.9 years; 50% men) in the exploratory cohort of sarcomeric mutation carriers without left ventricular hypertrophy., Results: In the primary cohort, maximal left ventricular wall thickness was 17±4 mm for adults and Z score 7.0±4.5 for children. Nineteen percent had late gadolinium enhancement on cardiac magnetic resonance. Mean peak oxygen consumption was 33 mL/kg per minute, and 92% of participants were New York Heart Association functional class I. New York Heart Association class II was associated with older age, MYH7 variants, and more prominent imaging abnormalities. Six previous trials of angiotensin receptor blockers in HCM enrolled a median of 24 patients (range, 19-133) with mean age of 51.2 years; 42% of patients were in New York Heart Association class ≥II, and sarcomeric mutations were not required., Conclusions: The VANISH cohort is much larger, younger, less heterogeneous, and has less advanced disease than prior angiotensin receptor blocker trials in HCM. Participants had relatively normal functional capacity and mild HCM features. New York Heart Association functional class II symptoms were associated with older age, more prominent imaging abnormalities, and MYH7 variants, suggesting both phenotype and genotype contribute to disease manifestations., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01912534.

Objectives: This study investigated the association between the use of evidence-based medicine (EBM) for heart failure (HF) and risk of workforce detachment., Background: The ability to work can be a marker of functional capacity and quality of life., Methods: We examined a nationwide cohort of patients in the workforce 1 year after first hospitalization for HF. EBM was defined as treatment with β-blockers and renin angiotensin system inhibitors. The fraction of target dose (0 TO 1) for each drug was calculated. The sum of the fractions gave each patient a score between 0 and 2. Patients were stratified into 4 groups according to this score: group 4 score = 2 (target dose of both drugs); group 3 score <2 to >1; group 2 score ≤1 to >0.5; and group 1 score ≤0.5. The risk of subsequent workforce detachment was estimated in cause specific Cox regression models., Results: One year after first HF hospitalization, 10,185 patients were part of the workforce, and 7,561 (74%) were in treatment with at least 1 of the components of EBM. During a median follow-up of 727 days, 2,698 individuals (36%) became detached from the workforce. Patients receiving more EBM had a significantly lower risk of workforce detachment compared with those receiving less EBM (group 4 hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.77 to 0.98; group 3 HR: 0.85; 95% CI: 0.77 to 0.94; and group 2 HR 0.92; 95% CI: 0.83 to 1.02), all compared to group 1., Conclusions: Patients in the workforce 1 year after first HF hospitalization and treated with target or near-target doses of EBM were associated with a significantly lower risk of subsequent workforce detachment., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)