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BACKGROUND: The effects of treatments for heart failure (HF) may vary among patients according to left ventricular ejection fraction (LVEF). In FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure), the nonsteroidal mineralocorticoid receptor antagonist finerenone reduced the risk of cardiovascular death and total worsening HF events in patients with HF with mildly reduced or preserved ejection fraction. We examined the effect of finerenone according to LVEF in FINEARTS-HF. METHODS: FINEARTS-HF was a randomized, placebo-controlled trial examining the efficacy and safety of finerenone in patients with HF and LVEF ≥40%. The treatment effect of finerenone was examined in prespecified analyses according to LVEF categories (<50%, ≥50% to <60%, and ≥60%) and with LVEF as a continuous variable. The primary outcome was a composite of total (first and recurrent) worsening HF events and cardiovascular death. RESULTS: Baseline LVEF data were available for 5993 of the 6001 participants in FINEARTS-HF. Mean and median LVEF were 53±8% and 53% (interquartile range, 46%–58%), respectively. LVEF was <50% in 2172 (36%), between 50% and <60% in 2674 (45%), and ≥60% in 1147 (19%). Patients with higher LVEF were older, were more commonly female, were less likely to have a history of coronary artery disease, and more frequently had a history of hypertension and chronic kidney disease compared with those with a lower LVEF. Finerenone reduced the risk of cardiovascular death and total HF events consistently across LVEF categories (LVEF <50% rate ratio, 0.84 [95% CI, 0.68–1.03]; LVEF ≥50% to <60% rate ratio, 0.80 [0.66–0.97]; and LVEF ≥60% rate ratio, 0.94 [0.70–1.25]; P interaction=0.70). There was no modification of the benefit of finerenone across the range of LVEF when analyzed as a continuous variable (P interaction=0.28). There was a similar consistent effect of finerenone on reducing the total number of worsening HF events (continuous P interaction=0.26). CONCLUSIONS: In patients with HF with mildly reduced or preserved ejection fraction, finerenone reduced the risk of cardiovascular death and worsening HF events, irrespective of LVEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04435626. URL: https://eudract.ema.europa.eu; Unique identifier: 2020-000306-29. [ABSTRACT FROM AUTHOR]

No randomized controlled trial has yet demonstrated a statistically significant reduction in mortality in patients with heart failure and mildly reduced ejection (HFmrEF) or heart failure and preserved ejection fraction (HFpEF), in contrast to the benefits observed in heart failure with reduced ejection fraction (HFrEF). However, this probably reflects the statistical power of trials to date to show an effect on mortality rather than mechanistic differences between HFmEF/HFpEF and HFrEF or differences in treatment efficacy. Compared to patients with HFrEF, those with HFmrEF/HFpEF have lower mortality rates and a smaller proportion of potentially modifiable cardiovascular deaths (as opposed to unmodifiable noncardiovascular deaths). In addition, some causes of cardiovascular deaths may not be reduced by treatments for HF. Therefore, the low rate of potentially modifiable deaths in patients with HFmrEF/HFpEF, compared with HFrEF, has made it challenging to demonstrate a reduction in death (or cardiovascular death) in trials to date. [ABSTRACT FROM AUTHOR]

Background: The English NHS data opt-out allows people to prevent use of their health data for purposes other than direct care. In 2021, the number of opt-outs increased in response to government-led proposals to create a centralised pseudonymised primary care record database. Aim: To describe the potential impact of NHS national data opt-outs in 2021 on health data research. Design & setting: We conducted a descriptive analysis of opt-outs using publicly available data and the potential consequences on research are discussed. Method: Trends in opt-outs in England were described by age, sex, and region. Using a hypothetical study, we explored statistical and epidemiological implications of opt-outs. Results: During the lead up to a key government-led deadline for registering opt-outs (from 31 May 2021-30 June 2021), 1 339 862 national data opt-outs were recorded; increasing the percentage of opt-outs in England from 2.77% to 4.97% of the population. Among females, percentage opt-outs increased by 83% (from 3.02% to 5.53%) compared with 76% in males (from 2.51% to 4.41%). Across age groups, the highest relative increase was among people aged 40-49 years, which rose from 2.89% to 6.04%. Considerable geographical variation was not clearly related to deprivation. Key research consequences of opt-outs include reductions in sample size and unpredictable distortion of observed measures of the frequency of health events or associations between these events. Conclusion: Opt-out rates varied by age, sex, and place. The impact of this and variation by other characteristics on research is not quantifiable. Potential effects of opt-outs on research and consequences for health policies based on this research must be considered when creating future opt-out solutions. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims Methods and results Conclusions In the absence of randomized trial evidence, we performed a large observational analysis of the association between beta‐blocker (BB) use and clinical outcomes in patients with heart failure (HF) and mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF).We pooled individual patient data from four large HFmrEF/HFpEF trials (I‐Preserve, TOPCAT, PARAGON‐HF, and DELIVER). The primary outcome was the composite of cardiovascular death or HF hospitalization. Among the 16 951 patients included, the mean left ventricular ejection fraction (LVEF) was 56.8%, and 13 400 (79.1%) had HFpEF (LVEF ≥50%). Overall, 12 812 patients (75.6%) received a BB. The median bisoprolol‐equivalent dose of BB was 5.0 (Q1–Q3: 2.5–5.0) mg with BB continuation rates of 93.1% at 2 years (in survivors). The unadjusted hazard ratio (HR) for the primary outcome did not differ between BB users and non‐users (HR 0.98, 95% confidence interval [CI] 0.91–1.05), but the adjusted HR was lower in BB users than non‐users (0.81, 95% CI 0.74–0.88), and this association was maintained across LVEF (pinteraction = 0.88). In subgroup analyses, the adjusted risk of the primary outcome was similar in BB users and non‐users with or without a history of myocardial infarction, hypertension, or a baseline heart rate <70 bpm. By contrast, a better outcome with BB use was seen in patients with atrial fibrillation compared to those without atrial fibrillation (pintreraction = 0.02).In this observational analysis of non‐randomized BB treatment, there was no suggestion that BB use was associated with worse HF outcomes in HFmrEF/HFpEF, even after extensive adjustment for other prognostic variables. [ABSTRACT FROM AUTHOR]

BACKGROUND: Finerenone improves outcomes in patients with heart failure and mildly reduced or preserved ejection fraction. It is important to understand the efficacy and safety of finerenone in these patients according to age. METHODS: The aim of this analysis was to evaluate the interaction between age and the efficacy and safety of finerenone in the FINEARTS-HF trial (Finerenone Trial to Investigate Efficacy and Safety Compared to Placebo in Patients With Heart Failure). A total of 6001 patients aged 40 to 97 years were stratified by quartile (Q1–Q4) of baseline age: Q1, 40 to 66 years (n=1581); Q2, 67 to 73 years (n=1587); Q3, 74 to 79 years (n=1421); and Q4, ≥80 years (n=1412). FINEARTS-HF evaluated the impact of age on the efficacy of finerenone with respect to the primary composite outcome of cardiovascular death and total (first and recurrent) heart failure events, including heart failure hospitalization or urgent heart failure event, along with secondary efficacy and safety outcomes. RESULTS: The incidence of primary outcomes increased with age. Finerenone reduced the risk of the primary outcome consistently across all age categories: rate ratio in Q1, 0.70 (95% CI, 0.53–0.92); Q2, 0.83 (95% CI, 0.64–1.07); Q3, 0.98 (95% CI, 0.76–1.26); and Q4, 0.85 (95% CI, 0.67–1.07); P interaction=0.27. Similarly, a consistent effect was observed for the components of the primary outcome. The mean increase in Kansas City Cardiomyopathy Questionnaire-total symptom score from baseline to 12 months was greater with finerenone than placebo, with a consistent effect across all age categories: mean placebo-corrected change in Q1, 2.87 (95% CI, 1.09–4.66); Q2, 1.24 (95% CI, −0.59 to 3.07); Q3, 0.94 (−0.98 to 2.86); and Q4, 1.24 (−0.90 to 3.38); P interaction=0.50. Adverse events were similar across all age categories. The odds of experiencing hypotension, elevated creatinine, or hyperkalemia (increased) or hypokalemia (decreased) related to finerenone did not differ by age. CONCLUSIONS: In the FINEARTS-HF trial, finerenone reduced the primary outcome and components of the primary outcome and improved symptoms across a wide age spectrum. In addition, finerenone was safe and well-tolerated, irrespective of age. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT04435626 and EudraCT 2020-000306-29. [ABSTRACT FROM AUTHOR]

An initial decline in estimated glomerular filtration rate (eGFR) often leads to reluctance to continue life-saving therapies in patients with heart failure (HF). The goal of this study was to describe the association between initial decline in eGFR and subsequent clinical outcomes in patients randomized to placebo or finerenone. In this prespecified analysis of FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure), we examined the association between initial decline in eGFR (≥15%) from randomization to 1 month and subsequent outcomes in patients assigned to finerenone or placebo. The primary outcome was the composite of total HF events and cardiovascular death. Among 5,587 patients with an eGFR measurement at both baseline and 1 month, 1,018 (18.2%) experienced a ≥15% decline in eGFR. The proportion of patients experiencing a ≥15% decline in eGFR was 23.0% with finerenone and 13.4% with placebo (OR: 1.95; 95% CI: 1.69-2.24; P < 0.001). After adjustment, an eGFR decline was associated with a higher risk of the primary outcome in patients assigned to placebo (adjusted rate ratio: 1.50; 95% CI: 1.20-1.89) but not in those assigned to finerenone (adjusted rate ratio: 1.07; 95% CI: 0.84-1.35; P interaction = 0.04). By contrast, the efficacy of finerenone was consistent across the range of change in eGFR from baseline to 1 month (P interaction = 0.50 for percent change in eGFR), and safety, including hyperkalemia, was similar regardless of an early eGFR decline. Although an initial decline in eGFR was associated with worse outcomes in patients assigned to placebo, this relationship was not as strong in those treated with finerenone. An early decline in eGFR can be anticipated with finerenone and should not automatically lead to the discontinuation of this disease-modifying therapy (FINEARTS-HF Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure [ NCT04435626 ]; A Multicenter, Randomized, Double-Bline, Parallel-Group, Placebo-Controlled Study to Evaluate the efficacy and safety of finerenone on morbidity and mortality in participants With Heart Failure [NYHA II-IV] and left ventricular ejection fraction ≥40% [EudraCT 2020-000306-29]). [Display omitted] [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion Beta‐blockers may inhibit neprilysin activity and conversely, neprilysin inhibition may have a sympatho‐inhibitory action. Consequently, sacubitril/valsartan may have a greater effect in patients not receiving a beta‐blocker compared to those treated with a beta‐blocker.We examined the effect of sacubitril/valsartan compared to enalapril on outcomes according to background beta‐blocker treatment in the 8399 patients with heart failure with reduced ejection fraction enrolled in PARADIGM‐HF. The primary outcome was time to first heart failure hospitalization or cardiovascular death. Compared to the 7811 patients taking a beta‐blocker, the 588 patients not receiving a beta‐blocker were older, more frequently female, but had a similar mean left ventricular ejection fraction and New York Heart Association class distribution, with little difference in N‐terminal pro‐B‐type natriuretic peptide. Patients not taking beta‐blockers had a higher rate of the primary endpoint than those taking beta‐blockers. The benefit of sacubitril/valsartan on the primary endpoint was evident in both the no beta‐blocker subgroup (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.45–0.82) and the beta‐blocker subgroup (HR 0.82, 95% CI 0.75–0.90; p‐interaction = 0.06). The respective HRs for cardiovascular death were 0.47 (95% CI 0.32–0.69) versus 0.84 (95% CI 0.75–0.95; p‐interaction <0.01) and for HF hospitalization 0.76 (95% CI 0.51–1.12) versus 0.80 (95% CI 0.71–0.90; p‐interaction = 0.73). For all‐cause death, the HR in the no beta‐blocker group was 0.50 (95% CI 0.36–0.71) compared to 0.89 (95% CI 0.80–0.99) in the beta‐blocker group (p‐interaction <0.01). Safety outcomes related to sacubitril/valsartan versus enalapril did not differ according to background beta‐blocker use.Sacubitril/valsartan may be more effective than enalapril in reducing the risk of death in patients not treated with a beta‐blocker compared to those treated with a beta‐blocker, but is effective regardless of beta‐blocker use.Clinical Trial Registration: ClinicalTrials.gov NCT01035255. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with excessive adipocyte-derived aldosterone secretion, independent of the classical renin-angiotensin-aldosterone cascade, and mineralocorticoid receptor antagonists may be more effective in patients with heart failure (HF) and obesity., Objectives: This study sought to examine the effects of the nonsteroidal mineralocorticoid receptor antagonist finerenone compared with placebo, according to body mass index (BMI) in FINEARTS-HF (FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure)., Methods: A total of 6,001 patients with HF with NYHA functional class II, III, and IV, a left ventricular ejection fraction of ≥40%, evidence of structural heart disease, and elevated natriuretic peptide levels were randomized to finerenone or placebo. BMI (kg/m 2 ) was examined using World Health Organization categories, namely, underweight/normal weight (<25.0 kg/m 2 ; n = 1,306); overweight (25.0-29.9 kg/m 2 ; n = 1,990); obesity class I (30.0-34.9 kg/m 2 ; n = 1,546); obesity class II (35.0-39.9 kg/m 2 ; n = 751); and obesity class III (≥40 kg/m 2 ; n = 395). The primary outcome was cardiovascular death and total worsening HF events., Results: Data on baseline BMI were available for 5,988 patients (median: 29.2 kg/m 2 ; Q1-Q3: 25.5-33.6 kg/m 2 ). Compared with patients who were underweight/normal weight, those with obesity class II or III had a higher risk of the primary outcome (underweight/normal weight, reference; overweight, unadjusted rate ratio: 0.96 [95% CI: 0.81-1.15]; obesity class I: 1.04 [95% CI: 0.86-1.26]; obesity class II-III: 1.26 [95% CI: 1.03-1.54]). The effect of finerenone on the primary outcome did not vary by baseline BMI (underweight/normal weight, rate ratio: 0.80 [95% CI: 0.62-1.04]; overweight: 0.91 [95% CI: 0.72-1.15]; obesity class I: 0.92 [95% CI: 0.72-1.19]; obesity class II-III: 0.67 [95% CI: 0.50-0.89]; P interaction  = 0.32). However, when BMI was examined as a continuous variable, the beneficial effect of finerenone seemed to be greater in those with a higher BMI (P interaction  = 0.005). A similar pattern was observed for total worsening HF events. Consistent effects across baseline BMI were observed for cardiovascular and all-cause death and improvement in the Kansas City Cardiomyopathy Questionnaire scores., Conclusions: In patients with HF with mildly reduced/preserved ejection fraction, the beneficial effects of finerenone on clinical events and symptoms were consistent, irrespective of BMI at baseline, possibly with a greater effect on the primary outcome in patients with higher BMI. (FINEARTS-HF [FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure]; NCT04435626)., Competing Interests: Funding Support and Author Disclosures FINEARTS-HF was funded by Bayer AG. The Steering Committees of the trial designed and oversaw their conduct in collaboration with the Sponsor. The primary analyses, interpretation of the data, and initial manuscript drafting were conducted independently by the academic team. Dr Butt has received advisory board honoraria from AstraZeneca and Bayer; has received consultant honoraria from Novartis and AstraZeneca; and has received travel grants from AstraZeneca. Dr Jhund has received speakers’ fees from AstraZeneca, Novartis, Alkem Metabolics, ProAdWise Communications, Sun Pharmaceuticals; has received advisory board fees from AstraZeneca, Boehringer Ingelheim, and Novartis; has received research funding from AstraZeneca, Boehringer Ingelheim, Analog Devices Inc, Roche Diagnostics; his employer the University of Glasgow has been remunerated for clinical trial work from AstraZeneca, Bayer AG, Novartis, and Novo Nordisk; and he is a director at GCTP Ltd. Dr Claggett has received personal consulting fees from Alnylam, Bristol Myers Squibb, Cardior, Cardurion, Corvia, CVRx, Eli Lilly, Intellia, and Rocket; and has served on a data safety monitoring board for Novo Nordisk. Dr Desai has received institutional research grants (to Brigham and Women’s Hospital) from Abbott, Alnylam, AstraZeneca, Bayer, Novartis, and Pfizer; and has received personal consulting fees from Abbott, Alnylam, AstraZeneca, Bayer, Biofourmis, Boston Scientific, Medpace, Medtronic, Merck, Novartis, Parexel, Porter Health, Regeneron, River2Renal, Roche, Veristat, Verily, and Zydus. Drs Viswanathan, Lage, Scheerer, and Lay-Flurrie are full-time employees of Bayer. Dr Lam has received research support from Novo Nordisk and Roche Diagnostics; has received consulting fees from Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, CPC Clinical Research, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corporation, Radcliffe Group Ltd., Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and, Us2.ai; and is a co-founder and nonexecutive director of Us2.ai. Dr Senni has served on advisory boards for, as a consultant for, and has received honoraria from Novartis, Abbott, Merck, MSD, Vifor, AstraZeneca, Cardurion, Novo Nordisk, Bayer, and Boehringer Ingelheim. Dr Shah has received research grants from the NIH (U54 HL160273, X01 HL169712, R01 HL140731, R01 HL149423), AHA (24SFRNPCN1291224), AstraZeneca, Corvia, and Pfizer; and has received consulting fees from Abbott, Alleviant, AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, and Ultromics. Dr Voors’ employer received consultancy fees and/or research support from Adrenomed, Anacardio, AstraZeneca, Bayer AG, BMS, Boehringer Ingelheim, Corteria, EliLilly, Merck, Moderna, Novartis, Novo Nordisk, Roche diagnostics, and SalubrisBio. Dr Bauersachs received honoraria for lectures/consulting from Novartis, Vifor, Bayer, Pfizer, Boehringer Ingelheim, AstraZeneca, Cardior, CVRx, BMS, Amgen, Corvia, Norgine, Edwards, and Roche not related to this paper; and has received research support for the department from Zoll, CVRx, Abiomed, Norgine, and Roche, not related to this paper. Dr Zannad has received personal fees from 89Bio, Abbott, Acceleron, Applied Therapeutics, Bayer, Betagenon, Boehringer, BMS, CVRx, Cambrian, Cardior, Cereno pharmaceutical, Cellprothera, CEVA, Inventiva, KBP, Merck, NovoNordisk, Owkin, Otsuka, Roche Diagnostics, Northsea, USa2; has stock options at G3Pharmaceutical; has equity in Cereno, Cardiorenal, and Eshmoun Clinical research; and is the founder of Cardiovascular Clinical Trialists. Dr Pitt is a consultant for Bayer, AstraZeneca, Boehringer Ingelheim, Lexicon, Bristol Myers Squibb, KBP Biosciences∗, Sarfez Pharmaceuticals∗, Pharmaceuticals∗, SQinnovations∗, G3 Pharmaceuticals, Sea Star medical∗, Vifor∗ Prointel∗, and Brainstorm Medical; has stock options in KBP Biosciences, Sarfez Pharmaceuticals, Pharmaceuticals, SQinnovations, Sea Star medical, Vifor, Prointel, and Brainstorm Medical; and has U.S. Patent 9931412-site specific delivery of eplerenone to the myocardium, and U.S. Patent pending 63/045,783 Histone modulating agents for the prevention and treatment of organ failure. Dr Vaduganathan has received research grant support, served on advisory boards, or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Milestone Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and participates on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. Dr Solomon has received research grants from Alexion, Alnylam, AstraZeneca, Bellerophon, Bayer, BMS, Boston Scientific, Cytokinetics, Edgewise, Eidos, Gossamer, GSK, Ionis, Lilly, MyoKardia, NIH/NHLBI, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, US2.AI; and has consulted for Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. Dr McMurray has received payments through Glasgow University from work on clinical trials; has receviedconsulting and grants from Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GSK and Novartis, British Heart Foundation, National Institute for Health – National Heart, Lung, and Blood Institute (NIH-NHLBI), Boehringer Ingelheim, SQ Innovations, and Catalyze Group; has receivedpersonal consultancy fees from Alynylam Pharmaceuticals, Amgen, AnaCardio, AstraZeneca, Bayer, Berlin Cures, BMS, Cardurion, Cytokinetics, Ionis Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, and River 2 Renal Corp; has received personal lecture fees from Abbott, Alkem Metabolics, Astra Zeneca, Blue Ocean Scientific Solutions Ltd., Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharmaceuticals Ltd., Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J.B. Chemicals & Pharmaceuticals Ltd, Lupin Pharmaceuticals, Medscape/Heart.Org., ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, and Translational Medicine Academy; and data safety monitoring board membership for WIRB-Copernicus Group Clinical Inc; andis a director of Global Clinical Trial Partners Ltd.All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Steroidal mineralocorticoid receptor antagonists reduce morbidity and mortality among patients with heart failure and reduced ejection fraction, but their efficacy in those with heart failure and mildly reduced or preserved ejection fraction has not been established. Data regarding the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist finerenone in patients with heart failure and mildly reduced or preserved ejection fraction are needed., Methods: In this international, double-blind trial, we randomly assigned patients with heart failure and a left ventricular ejection fraction of 40% or greater, in a 1:1 ratio, to receive finerenone (at a maximum dose of 20 mg or 40 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of total worsening heart failure events (with an event defined as a first or recurrent unplanned hospitalization or urgent visit for heart failure) and death from cardiovascular causes. The components of the primary outcome and safety were also assessed., Results: Over a median follow-up of 32 months, 1083 primary-outcome events occurred in 624 of 3003 patients in the finerenone group, and 1283 primary-outcome events occurred in 719 of 2998 patients in the placebo group (rate ratio, 0.84; 95% confidence interval [CI], 0.74 to 0.95; P = 0.007). The total number of worsening heart failure events was 842 in the finerenone group and 1024 in the placebo group (rate ratio, 0.82; 95% CI, 0.71 to 0.94; P = 0.006). The percentage of patients who died from cardiovascular causes was 8.1% and 8.7%, respectively (hazard ratio, 0.93; 95% CI, 0.78 to 1.11). Finerenone was associated with an increased risk of hyperkalemia and a reduced risk of hypokalemia., Conclusions: In patients with heart failure and mildly reduced or preserved ejection fraction, finerenone resulted in a significantly lower rate of a composite of total worsening heart failure events and death from cardiovascular causes than placebo. (Funded by Bayer; FINEARTS-HF ClinicalTrials.gov number, NCT04435626.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Finerenone has kidney protective effects in patients with chronic kidney disease (CKD) with type 2 diabetes, but effects on kidney outcomes in patients with heart failure (HF) with and without diabetes and/or CKD are not known., Objectives: Examine the effects of finerenone on kidney outcomes in FINEARTS-HF, a randomized trial of finerenone vs. placebo among patients with HF with mildly reduced or preserved ejection fraction., Methods: We explored the effects of finerenone on the secondary outcome of a sustained ≥50% eGFR decline or kidney failure (sustained eGFR decline <15 mL/min/1.73 m 2 ; initiation of maintenance dialysis; renal transplant). In this prespecified analysis, we also report effects of finerenone on: 1) sustained ≥57% eGFR decline or kidney failure; 2) eGFR slope; 3) changes in urine albumin/creatinine ratio (UACR)., Results: Among 6,001 participants, mean baseline eGFR was 62 ±20mL/min/1.73m 2 ; 48% had eGFR <60mL/min/1.73m 2 . Overall, 5,797 had baseline UACR data (median 18 [7,67]mg/g). Over 2.6 years median follow-up, the incidence of the composite kidney outcome (≥50% eGFR decline or kidney failure) was numerically, but non-significantly, higher for finerenone vs. placebo (75 vs. 55 events; HR 1.33; 95%CI 0.94, 1.89). Similar results were observed for the composite of ≥57% eGFR decline or kidney failure (41 vs. 31 events; HR 1.28; 95%CI 0.80, 2.05), though the overall event frequency was relatively low. During the first 3 months, finerenone led to an acute decline in eGFR of -2.9 mL/min/1.73m 2 (95%CI -3.4, -2.4) but did not alter chronic (from 3 months) eGFR slope (+0.2 mL/min/1.73m 2 /year; 95%CI -0.1, +0.4), vs. placebo. The difference in total slope was -0.7 (95%CI -0.9 to -0.4) mL/min/1.73 m 2 /year. Finerenone reduced UACR by 30% (95%CI 25%, 34%) over 6 months vs. placebo, an effect that persisted throughout follow-up. Finerenone reduced the risk of new-onset of micro- and macroalbuminuria by 24% (HR 0.76; 95%CI 0.68, 0.83) and 38% (HR 0.62; 95%CI 0.53, 0.73), respectively., Conclusions: In FINEARTS-HF, a population at low risk of adverse kidney outcomes, finerenone did not significantly modify the kidney composite outcomes. Finerenone led to a greater reduction in initial eGFR, but did not result in a significant difference in chronic eGFR slope, vs. placebo. Finerenone led to early and sustained reductions in albuminuria and reduced the risk of new-onset micro- and macroalbuminuria., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To examine the impact of the COVID-19 pandemic on deprivation-related inequalities in hospitalisations for cardiovascular disease (CVD) conditions in Denmark and England between March 2018 and December 2021., Design: Time-series studies in England and Denmark., Setting: With the approval of National Health Service England, we used English primary care electronic health records, linked to secondary care and death registry data through the OpenSAFELY platform and nationwide Danish health registry data., Participants: We included adults aged 18 and over without missing age, sex or deprivation information. On 1 March 2020, 16 234 700 people in England and 4 491 336 people in Denmark met the inclusion criteria., Primary Outcome Measures: Hospital admissions with the primary reason for myocardial infarction (MI), ischaemic or haemorrhagic stroke, heart failure and venous thromboembolism (VTE)., Results: We saw deprivation gradients in monthly CVD hospitalisations in both countries, with differences more pronounced in Denmark. Based on pre-pandemic trends, in England, there were an estimated 2608 fewer admissions than expected for heart failure in the most deprived quintile during the pandemic compared with an estimated 979 fewer admissions in the least deprived quintile. For all other outcomes, there was little variation by deprivation quintile. In Denmark, there were an estimated 1013 fewer admissions than expected over the pandemic for MI in the most deprived quintile compared with 619 in the least deprived quintile. Similar trends were seen for stroke and VTE, though absolute numbers were smaller. Heart failure admissions were similar to pre-pandemic levels with little variation by deprivation quintile., Conclusions: Overall, we did not find that the pandemic substantially worsened pre-existing deprivation-related differences in CVD hospitalisations, though there were exceptions in both countries., Competing Interests: Competing interests: REC has personal shares in AstraZeneca (AZ) unrelated to this work. BM is also employed by National Health Service ( NHS) England (all declarations are openly available at: https://www.whopaysthisdoctor.org/doctor/491/active ). JH has grant funding from UKRI and the Wellcome Trust, has a patent with Juli Health unrelated to this work and has received consultancy fees from Juli Health and the Wellcome Trust unrelated to this work. RM is supported by Barts Charity (MGU0504), receives salary contributions from Genes & Health and has received consultancy fees from Amgen. JKQ has grants from MRC, HDR UK, GlaxoSmithKline (GSK), BI, Asthma + Lung UK and AZ and has received fees from GSK, Evidera, AZ and Insmed. SL was co-founder and co-chair of the RECORD steering committee and has a leadership role at Health Data Research UK. KM has received consultancy fees from Amgen. LAT has grant funding from MRC, the Wellcome Trust, has consulted for Bayer and is on the MHRA expert advisory group (Women’s health) and is a member of four non-industry funded trial advisory committees (unpaid). AYSW is funded by British Heart Foundation (FS/19/19/34175) and AIR@InnoHK administered by Innovation and Technology Commission. AM has received consultancy fees from induction health and is a member of RCGP health informatics group and the NHS Digital GP data Professional Advisory Group. Department of Clinical Epidemiology, Aarhus University, receives funding for other studies from companies in the form of research grants to (and administered by) Aarhus University. None of these studies have any relation to the present study. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Patients with heart failure (HF) are limited by symptoms and have impaired quality of life. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a patient-reported outcome measure that enables evaluation of the effect of HF and the impact of new therapies on health status in patients with HF., Objectives: This prespecified analysis of FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure) assessed the efficacy and safety of finerenone according to baseline KCCQ Total Symptom Score (TSS) and the effect of finerenone on KCCQ-TSS., Methods: FINEARTS-HF tested the efficacy of the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone, compared with placebo, in patients with HF with mildly reduced ejection fraction/preserved ejection fraction. The primary endpoint was the composite of cardiovascular death and total worsening HF events. The KCCQ was completed by patients at randomization and at 6, 9, and 12 months after randomization. Change in KCCQ-TSS was a key secondary endpoint. Patients were stratified by KCCQ-TSS tertiles at baseline. The association between KCCQ tertile and clinical outcomes was evaluated using semiparametric proportional-rates models for total events and Cox models for time-to-first-event data, and the effects of finerenone vs placebo on the primary endpoint were assessed across tertiles of KCCQ-TSS., Results: Of the 6,001 participants in FINEARTS-HF, 5,986 (99.8%) had baseline KCCQ-TSS recorded (median score 69.8 of a possible 100; higher score = better health status). Lower (worse) KCCQ-TSS was associated with a higher risk of the primary endpoint. Finerenone, compared with placebo, reduced the risk of the primary endpoint across the range of KCCQ-TSS: tertile 1 (score 0-<57): RR: 0.82 (95% CI: 0.68-1.00); tertile 2 (57-<81): 0.88 (95% CI: 0.70-1.11); tertile 3 (81-100): 0.88 (95% CI: 0.69-1.14) (P interaction  = 0.89). Compared with placebo, finerenone significantly improved KCCQ-TSS from baseline with a mean difference at 12 months of 1.62 points (95% CI: 0.69-2.56 points) (P < 0.001). Numerically fewer finerenone-treated patients experienced clinically meaningful deterioration, and more had improvements in KCCQ-TSS., Conclusions: Finerenone significantly reduced HF events and improved health status in patients with HF and mildly reduced ejection fraction/preserved ejection fraction across the spectrum of KCCQ-TSS at baseline. (Study to Evaluate the Efficacy [Effect on Disease] and Safety of Finerenone on Morbidity [Events Indicating Disease Worsening] & Mortality [Death Rate] in Participants With Heart Failure and Left Ventricular Ejection Fraction [Proportion of Blood Expelled Per Heart Stroke] Greater or Equal to 40% [FINEARTS-HF], NCT04435626; Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure; EudraCT 2020-000306-29)., Competing Interests: Funding Support and Author Disclosures The FINEARTS-HF trial was funded by Bayer. Dr Yang has received Global CardioVascular Clinical Trialists (CVCT) Young Trialist Grant and travel grants from AstraZeneca and Bayer. Dr Atherton has received other support from Bayer, during the conduct of the study; and has received other support from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Novo Nordisk, Vifor Pharma, and Merck Sharp and Dome, outside of the submitted work. Dr Chiang has received personal fees from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Menarini, Merck Sharp and Dohme, Novartis, Pfizer, and Sanofi. Dr Chopra has received modest speaker fees from Boehringer, AstraZeneca, Novartis, Pfizer, Novo Nordisk, Glenmark, Sun, Mankind, Lupin, Alembic, JB, Reddy’s, Intas, Eris, and Cipla, outside of the submitted work. Dr Comin-Colet has received personal fees from Bayer, during the conduct of the study; has received grants from Novartis, Vifor Pharma, AstraZeneca, and Orion Pharma; and has received personal fees from Bayer, Boehringer Ingelheim, Vifor Pharma, Novartis, AstraZeneca, and Orion Pharma, outside the submitted work. Dr Kosiborod has received research grant support from AstraZeneca, Boehringer Ingelheim, and Pfizer; has served as a consultant or on an advisory board for Alnylam, Amgen, Applied Therapeutics, Arrowhead Pharmaceuticals, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Cytokinetics, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pfizer, Pharmacosmos, Sanofi, and Vifor Pharma; has received other research support from AstraZeneca and Vifor; and has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr Saraiva has received grants or fees for working on clinical trials, consultancy, advisory board or steering committee membership, and other activities from AstraZeneca, Novo Nordisk, Bayer, Boehringer Ingelheim, Novartis, Merck Sharp and Dohme, and Janssen. Dr Claggett has received personal consulting fees from Alnylam, Bristol Myers Squibb, Cardior, Cardurion, Corvia, CVRx, Eli Lilly, Intellia, and Rocket; and has served on a data safety monitoring board for Novo Nordisk. Dr Desai has received institutional research grants (to Brigham and Women’s Hospital) from Abbott, Alnylam, AstraZeneca, Bayer, Novartis, and Pfizer; and has received personal consulting fees from Abbott, Alnylam, AstraZeneca, Bayer, Biofourmis, Boston Scientific, Medpace, Medtronic, Merck, Novartis, Parexel, Porter Health, Regeneron, River2Renal, Roche, Veristat, Verily, and Zydus. Dr Lam has received research support from Novo Nordisk and Roche Diagnostics; has received consulting fees from Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, CPC Clinical Research, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research and Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corporation, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and is a cofounder and non-executive director of Us2.ai. Dr Senni has served on advisory boards for, served as a consultant for, and received honoraria from Novartis, Abbott, Merck, Merck Sharp and Dohme, Vifor, AstraZeneca, Cardurion, Novo Nordisk, Bayer, and Boehringer Ingelheim. Dr Shah has received research grants from National Institutes of Health (U54 HL160273, X01 HL169712, R01 HL140731, R01 HL149423), AHA (24SFRNPCN1291224), AstraZeneca, Corvia, and Pfizer; and has received consulting fees from Abbott, Alleviant, AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, and Ultromics. Dr Voors’ employer has received consultancy fees and/or research support from Adrenomed, Anacardio, AstraZeneca, Bayer AG, Bristol Myers Squibb, Boehringer Ingelheim, Corteria, EliLilly, Merck, Moderna, Novartis, Novo Nordisk, Roche Diagnostics, and SalubrisBio. Dr Zannad has received personal fees from 89Bio, Abbott, Acceleron, Applied Therapeutics, Bayer, Betagenon, Boehringer, Bristol Myers Squibb, CVRx, Cambrian, Cardior, Cereno Pharmaceutical, Cellprothera, CEVA, Inventiva, KBP, Merck, Novo Nordisk, Owkin, Otsuka, Roche Diagnostics, Northsea, and USa2; has stock options at G3Pharmaceutical; has equities at Cereno, Cardiorenal, and Eshmoun Clinical research; and is the founder of Cardiovascular Clinical Trialists. Dr Pitt is a consultant for Bayer, AstraZeneca, Boehringer Ingelheim, Lexicon, Bristol Myers Squibb, KBP Biosciences, Sarfez Pharmaceuticals, Pharmaceuticals, SQinnovations, G3 Pharmaceuticals, Sea Star medical, Vifor Prointel, and Brainstorm Medical; has stock/stock options in KBP Biosciences, Sarfez Pharmaceuticals, Pharmaceuticals, SQinnovations, G3 Pharmaceuticals, Sea Star medical, Vifor Prointel, and Brainstorm Medical; and has U.S. Patent 9931412-site specific delivery of eplerenone to the myocardium, U.S. Patent pending 63/045,783 Histone modulating agents for the prevention and treatment of organ failure. Dr Vaduganathan has received research grant support, served on advisory boards, or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Milestone Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and participates on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. Drs Jhund and McMurray are supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217 and the Vera Melrose Heart Failure Research Fund. Dr Jhund has received speakers’ fees from AstraZeneca, Novartis, Alkem Metabolics, ProAdWise Communications, and Sun Pharmaceuticals; has received advisory board fees from AstraZeneca, Boehringer Ingelheim, and Novartis; has received research funding from AstraZeneca, Boehringer Ingelheim, Analog Devices Inc, and Roche Diagnostics; his employer, the University of Glasgow, has been remunerated for clinical trial work from AstraZeneca, Bayer AG, Novartis, and Novo Nordisk; and is Director of GCTP Ltd. Dr Solomon has received research grants from Alexion, Alnylam, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Boston Scientific, Cytokinetics, Edgewise, Eidos, Gossamer, GlaxoSmithKline, Ionis, Lilly, MyoKardia, National Institutes of Health/NHLBI, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. Dr McMurray has received payments through Glasgow University from work on clinical trials, as well as consulting fees and grants from Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GlaxoSmithKline, Novartis, British Heart Foundation, National Institute for Health–National Heart, Lung, and Blood Institute, Boehringer Ingelheim, SQ Innovations, and Catalyze Group; has received personal consultancy fees from Alnylam Pharmaceuticals, Amgen, AnaCardio, AstraZeneca, Bayer, Berlin Cures, Bristol Myers Squibb, Cardurion, Cytokinetics, Ionis Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, and River 2 Renal Corp; has received personal lecture fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions Ltd, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharmaceuticals Ltd, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J.B. Chemicals and Pharmaceuticals Ltd, Lupin Pharmaceuticals, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, Translational Medicine Academy; has served on the Data Safety Monitoring Board for WIRB-Copernicus Group Clinical Inc; and is a director of Global Clinical Trial Partners Ltd. Drs. Kolkhof, Viswanathan, Lage, and Rohwedder are employees of Bayer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with heart failure (HF) with mildly reduced or preserved ejection fraction face heightened long-term risks of morbidity and mortality. The sodium glucose-co-transporter-2 inhibitors (SGLT2i) and the non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone have both been shown to reduce the risk of cardiovascular events in this population, but the effects of their combined use are not known., Methods: FINEARTS-HF was a randomized, double-blind, placebo-controlled trial of finerenone in patients with HF and left ventricular ejection fraction (LVEF) ≥40%. Baseline SGLT2i use was a prespecified subgroup. The primary outcome was a composite of total (first and recurrent) worsening HF events and cardiovascular death. We first assessed for evidence of treatment heterogeneity based on baseline SGLT2i use. We further examined SGLT2i uptake during the trial and evaluated the treatment effects of finerenone accounting for baseline and during trial use of SGLT2i in time-varying analyses., Results: Among 6,001 participants, 817 (13.6%) were treated with an SGLT2i at baseline. During 2.6-years median follow-up, treatment with finerenone similarly reduced the risk of the primary outcome in participants treated with an SGLT2i (rate ratio 0.83; 95% confidence interval 0.60 to 1.16) and without an SGLT2i at baseline (rate ratio 0.85; 95% confidence interval 0.74 to 0.98); P interaction =0.76. In follow-up, 980 participants initiated SGLT2i, which was less frequent in the finerenone arm compared with placebo (17.7% vs. 20.1%; hazard ratio 0.86; confidence interval 0.76 to 0.97). Time-updated analyses accounting for baseline and subsequent use of SGLT2i did not meaningfully alter the treatment effects of finerenone on the primary endpoint., Conclusions: The treatment benefits of the non-steroidal MRA finerenone were observed irrespective of concomitant use of an SGLT2i. These data suggest that the combined use of SGLT2i and a non-steroidal MRA may provide additive protection against cardiovascular events in patients with HF with mildly reduced or preserved ejection fraction.

Background: Long COVID is a major problem affecting patient health, the health service, and the workforce. To optimise the design of future interventions against COVID-19, and to better plan and allocate health resources, it is critical to quantify the health and economic burden of this novel condition. We aimed to evaluate and estimate the differences in health impacts of long COVID across sociodemographic categories and quantify this in Quality-Adjusted Life-Years (QALYs), widely used measures across health systems., Methods: With the approval of NHS England, we utilised OpenPROMPT, a UK cohort study measuring the impact of long COVID on health-related quality-of-life (HRQoL). OpenPROMPT invited responses to Patient Reported Outcome Measures (PROMs) using a smartphone application and recruited between November 2022 and October 2023. We used the validated EuroQol EQ-5D questionnaire with the UK Value Set to develop disutility scores (1-utility) for respondents with and without Long COVID using linear mixed models, and we calculated subsequent Quality-Adjusted Life-Months (QALMs) for long COVID., Findings: The total OpenPROMPT cohort consisted of 7575 individuals who consented to data collection, with which we used data from 6070 participants who completed a baseline research questionnaire where 24.6% self-reported long COVID. In multivariable regressions, long COVID had a consistent impact on HRQoL, showing a higher likelihood or odds of reporting loss in quality-of-life (Odds Ratio (OR): 4.7, 95% CI: 3.72-5.93) compared with people who did not report long COVID. Reporting a disability was the largest predictor of losses of HRQoL (OR: 17.7, 95% CI: 10.37-30.33) across survey responses. Self-reported long COVID was associated with an 0.37 QALM loss., Interpretation: We found substantial impacts on quality-of-life due to long COVID, representing a major burden on patients and the health service. We highlight the need for continued support and research for long COVID, as HRQoL scores compared unfavourably to patients with conditions such as multiple sclerosis, heart failure, and renal disease., Funding: This research was supported by the National Institute for Health and Care Research (NIHR) (OpenPROMPT: COV-LT2-0073)., Competing Interests: BG has received funding via the University of Oxford from a wide range of public and charitable funders: the NHS National Institute for Health Research (NIHR), NHS England, the NIHR School of Primary Care Research, the NIHR Oxford Biomedical Research Centre, the Peter Bennett Foundation, the Laura and John Arnold Foundation, the Mohn-Westlake Foundation, NIHR Applied Research Collaboration Oxford and Thames Valley, UKRI/MRC, the Wellcome Trust, the Good Thinking Foundation, Health Data Research UK, the Health Foundation, and the World Health Organisation; he also receives personal income from speaking and writing for lay audiences on the misuse of science. He led the Goldacre Review (“Better, broader, safer: using health data for research and analysis” March 2022) for Secretary Of State for Health and Social Care; I chaired the HealthTech Advisory Board for Sec of State; I was a Non-Executive Director at NHS Digital; I am on the UKHSA Data Science Advisory Board; I have sat on various other local and national committees in the public sector. BMK is also employed by NHS England working on medicines policy and clinical lead for primary care medicines data. AM is a senior clinical researcher at the University of Oxford in the Bennett Institute, which is funded by contracts and grants obtained from the Bennett Foundation, Wellcome Trust, NIHR Oxford Biomedical Research Centre, NIHR Applied Research Collaboration Oxford and Thames Valley, Mohn-Westlake Foundation, and NHS England, and has consulted for health care vendors, the last time in 2022; the companies consulted in the last 3 years have no relationship to OpenSAFELY; he has represented the RCGP in the health informatics group and the Profession Advisory Group that advises on access to GP Data for Pandemic Planning and Research (GDPPR); the latter was a paid role; and he is a former employee and interim Chief Medical Officer of NHS Digital. REC holds shares in AstraZeneca. AB has received consulting fees from AstraZeneca, Roche, Takeda, Daiichi-Sankyo, Eisai, Novartis, Idorsia and Rhythmn. LAT has received grants or contracts from MRC, Wellcome, NIHR and GSK for an epidemiological study of kidney disease (no personal payment received) and has consulted for Bayer in relation to an observational study of chronic kidney disease (no personal payment received); she has received support for attending the MHRA Expert advisory group on Women's health and is an unpaid member of 4 non-industry funded NIHR/MRC trial advisory committees. JP has acted as an expert witness for the GMC with all fees paid to the company, and is an employee of TPP who provide the SystmOne software. MJ received support from NIHR for the funding of this manuscript and has received research grants from BMGF, Gavi, RCUK, WHO, Wellcome Trust, European Commission, InnoHK, TFGH and CDC. All other authors declare no competing interests., (© 2024 The Authors. Published by Elsevier Ltd.)