| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 6. |
- Munn-Chernoff, M. A., et al.
(författare)
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- 2021
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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- Jimenez, J. L., et al.
(författare)
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Evolution of Organic Aerosols in the Atmosphere
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 326:5959, s. 1525-1529
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Tidskriftsartikel (refereegranskat)abstract
- Organic aerosol (OA) particles affect climate forcing and human health, but their sources and evolution remain poorly characterized. We present a unifying model framework describing the atmospheric evolution of OA that is constrained by high-time-resolution measurements of its composition, volatility, and oxidation state. OA and OA precursor gases evolve by becoming increasingly oxidized, less volatile, and more hygroscopic, leading to the formation of oxygenated organic aerosol (OOA), with concentrations comparable to those of sulfate aerosol throughout the Northern Hemisphere. Our model framework captures the dynamic aging behavior observed in both the atmosphere and laboratory: It can serve as a basis for improving parameterizations in regional and global models.
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| 12. |
- McMurray, J. J. V., et al.
(författare)
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Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction
- 2019
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 381:21, s. 1995-2008
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes.METHODS In this phase 3, placebo-controlled trial, we randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either dapagliflozin (at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death.RESULTS Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). A first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin group and in 326 patients (13.7%) in the placebo group (hazard ratio, 0.70; 95% CI, 0.59 to 0.83). Death from cardiovascular causes occurred in 227 patients (9.6%) in the dapagliflozin group and in 273 patients (11.5%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98); 276 patients (11.6%) and 329 patients (13.9%), respectively, died from any cause (hazard ratio, 0.83; 95% CI, 0.71 to 0.97). Findings in patients with diabetes were similar to those in patients without diabetes. The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups.CONCLUSIONS Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes.
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| 13. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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| 14. |
- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 15. |
- Inzucchi, S. E., et al.
(författare)
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Dapagliflozin and the incidence of type 2 diabetes in patients with heart failure and reduced ejection fraction: An exploratory analysis from DAPA-HF
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:2, s. 586-594
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE The sodium–glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of cardiovascular mortality and worsening heart failure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. This report explores the effect of dapagliflozin on incident type 2 diabetes (T2D) in the cohort without diabetes enrolled in the trial. RESEARCH DESIGN AND METHODS The subgroup of 2,605 patients with heart failure and reduced ejection fraction (HFrEF), no prior history of diabetes, and an HbA1c of <6.5% at baseline was randomized to dapagliflozin 10 mg daily or placebo. In this exploratory analysis, surveillance for new-onset diabetes was accomplished through periodic HbA1c testing as part of the study protocol and comparison between the treatment groups assessed through a Cox proportional hazards model. RESULTS At baseline, the mean HbA1c was 5.8%. At 8 months, there were minimal changes, withaplacebo-adjusted change inthedapagliflozin groupof20.04%. Over a median follow-up of 18 months, diabetes developed in 93 of 1,307 patients (7.1%) in the placebogroup and 64 of 1,298 (4.9%) in the dapagliflozingroup. Dapagliflozin led to a 32% reduction in diabetes incidence (hazard ratio 0.68, 95% CI 0.50–0.94; P 5 0.019). More than 95% of the participants who developed T2D had prediabetes at baseline (HbA1c 5.7–6.4%). Participants who developed diabetes in DAPA-HF had a higher subsequent mortality than those who did not. CONCLUSIONS In this exploratory analysis among patients with HFrEF, treatment with dapagliflozin reduced the incidence of new diabetes. This potential benefit needs confirmation in trials of longer duration and in people without heart failure. © 2020 by the American Diabetes Association.
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| 16. |
- Shen, L., et al.
(författare)
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Prior Pacemaker Implantation and Clinical Outcomes in Patients With Heart Failure and Preserved Ejection Fraction
- 2019
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Ingår i: Jacc-Heart Failure. - : Elsevier BV. - 2213-1779. ; 7:5, s. 418-427
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES This study examined the relationship between prior pacemaker implantation and clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). BACKGROUND Conventional right ventricular pacing causes electrical and mechanical left ventricular dyssynchrony and may worsen left ventricular systolic dysfunction and HF. Whether conventional pacing is also associated with worse outcomes in HFpEF is unknown. METHODS Patient data were pooled from the CHARM-Preserved (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity), I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction), and TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial) studies and were examined for the association between having a pacemaker and the risk of the primary composite of cardiovascular death or HF hospitalization, the individual components of the composite, the 2 main modes of cardiovascular death (i.e., sudden death and pump failure death), and all-cause death in unadjusted and adjusted analyses. RESULTS Of the 8,466 patients included, 682 patients (8%) had a pacemaker. Pacemaker patients were older and more often men and had lower body mass indexes, estimated glomerular filtration rates, and blood pressures but higher concentrations of N-terminal pro-B-type natriuretic peptide than those without a pacemaker. The rate of the primary composite outcome in pacemaker patients was almost twice that in patients without a pacemaker (13.6 vs. 7.6 per 100 patient-years of follow up, respectively), with a similar finding for HF hospitalizations (10.8 vs. 5.1 per 100 patient-years, respectively). This risk rate persisted after adjusting for other prognostic variables (hazard ratio [HR] for the composite outcome: 1.17; 95% confidence interval [CI]: 1.02 to 1.33; p = 0.026), driven mainly by HF hospitalization (HR: 1.37; 95% CI: 1.17 to 1.60; p < 0.001). The risk of death was not significantly higher in pacemaker patients in the adjusted analyses. CONCLUSIONS These findings raise the possibility that right ventricular pacing-induced left ventricular dyssynchrony may be detrimental in HFpEF patients. (C) 2019 by the American College of Cardiology Foundation.
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| 17. |
- Soda, T., et al.
(författare)
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International Consortium on the Genetics of Electroconvulsive Therapy and Severe Depressive Disorders (Gen-ECT-ic)
- 2020
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Ingår i: European Archives of Psychiatry and Clinical Neuroscience. - : Springer Science and Business Media LLC. - 0940-1334 .- 1433-8491. ; 270:7, s. 921-932
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines. This is perhaps because ECT has controlled risk and logistical demands including use of general anaesthesia and muscle relaxants and side-effects such as short-term memory impairment. Better understanding of the genetics and biology of ECT response and of cognitive side-effects could lead to more personalized treatment decisions. To enhance the understanding of the genomics of severe depression and ECT response, researchers and ECT providers from around the world and from various depression or ECT networks, but not limited to, such as the Psychiatric Genomics Consortium, the Clinical Alliance and Research in ECT, and the National Network of Depression Centers have formed the Genetics of ECT International Consortium (Gen-ECT-ic). Gen-ECT-ic will organize the largest clinical and genetic collection to date to study the genomics of severe depressive disorders and response to ECT, aiming for 30,000 patients worldwide using a GWAS approach. At this stage it will be the largest genomic study on treatment response in depression. Retrospective data abstraction and prospective data collection will be facilitated by a uniform data collection approach that is flexible and will incorporate data from many clinical practices. Gen-ECT-ic invites all ECT providers and researchers to join its efforts.
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| 18. |
- Curtain, J. P., et al.
(författare)
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Effect of sacubitril/valsartan on investigator-reported ventricular arrhythmias in PARADIGM-HF
- 2022
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:3, s. 551-561
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Tidskriftsartikel (refereegranskat)abstract
- Aims Sudden death is a leading cause of mortality in heart failure with reduced ejection fraction (HFrEF). In PARADIGM-HF, sacubitril/valsartan reduced the incidence of sudden death. The purpose of this post hoc study was to analyse the effect of sacubitril/valsartan, compared to enalapril, on the incidence of ventricular arrhythmias. Methods and results Adverse event reports related to ventricular arrhythmias were examined in PARADIGM-HF. The effect of randomized treatment on two arrhythmia outcomes was analysed: ventricular arrhythmias and the composite of a ventricular arrhythmia, implantable cardioverter defibrillator (ICD) shock or resuscitated cardiac arrest. The risk of death related to a ventricular arrhythmia was examined in time-updated models. The interaction between heart failure aetiology, or baseline ICD/cardiac resynchronization therapy-defibrillator (CRT-D) use, and the effect of sacubitril/valsartan was analysed. Of the 8399 participants, 333 (4.0%) reported a ventricular arrhythmia and 372 (4.4%) the composite arrhythmia outcome. Ventricular arrhythmias were associated with higher mortality. Compared with enalapril, sacubitril/valsartan reduced the risk of a ventricular arrhythmia (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.62-0.95; p = 0.015) and the composite arrhythmia outcome (HR 0.79, 95% CI 0.65-0.97; p = 0.025). The treatment effect was maintained after adjustment and accounting for the competing risk of death. Baseline ICD/CRT-D use did not modify the effect of sacubitril/valsartan, but aetiology did: HR in patients with an ischaemic aetiology 0.93 (95% CI 0.71-1.21) versus 0.53 (95% CI 0.37-0.78) in those without an ischaemic aetiology (p for interaction = 0.020). Conclusions Sacubitril/valsartan reduced the incidence of investigator-reported ventricular arrhythmias in patients with HFrEF. This effect may have been greater in patients with a non-ischaemic aetiology.
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| 19. |
- Curtain, J. P., et al.
(författare)
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Prevalent and Incident Anemia in PARADIGM-HF and the Effect of Sacubitril/Valsartan
- 2023
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Ingår i: Jacc-Heart Failure. - 2213-1779. ; 11:7, s. 749-759
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Anemia is common in patients with heart failure with reduced ejection fraction and is associated with poor clinical outcomes. Renin-angiotensin system blockers lower hemoglobin and may induce anemia. OBJECTIVES The authors investigated whether concomitant neprilysin inhibition might ameliorate this effect of renin-angiotensin system blockers in PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure). METHODS Anemia was defined as hemoglobin <120 g/L in women and <130 g/L in men at screening. The authors investigated the effect of randomized treatment on clinical outcomes according to anemia status, change in hemoglobin from baseline, and the incidence of anemia. RESULTS Of 8,239 participants with a baseline hemoglobin measurement, 1,677 (20.4%) were anemic. Patients with anemia had a more severe heart failure profile, worse kidney function, greater neurohormonal derangement, and worse clinical outcomes. Sacubitril/valsartan, compared with enalapril, decreased the risk of cardiovascular death or heart failure hospitalization similarly in patients with (HR: 0.84; 95% CI: 0.71-1.00) and without anemia (HR: 0.78 [95% CI: 0.71-0.87]; P value for interaction 1/4 0.478). Between baseline and 12 months, hemoglobin decreased by 1.5 g/L (95% CI: 1.2-1.7 g/L) with sacubitril/valsartan compared with 2.3 g/L (95% CI: 2.0-2.6 g/L) with enalapril: mean difference 0.8 g/L (95% CI: 0.5-1.2 g/L; P < 0.001). Patients assigned to sacubitril/valsartan were less likely to develop anemia at 12 months (321 of 2,806 [11.4%]) compared with patients randomized to enalapril (440 of 2,824 [15.6%]) (OR: 0.70 [95% CI: 0.60-0.81]; P < 0.001). These findings were similar in PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) (sacubitril/valsartan vs valsartan). There was biomarker evidence of increased iron utilization with sacubitril/valsartan. CONCLUSIONS Irrespective of anemia status, sacubitril/valsartan compared with enalapril, decreased mortality and hospitalization. Hemoglobin decreased less with sacubitril/valsartan and the incidence of new anemia was lower with sacubitril/valsartan.
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| 20. |
- Jackson, Alice M., et al.
(författare)
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Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF.
- 2020
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Ingår i: Circulation. - 1524-4539. ; 142:11, s. 1040-1054
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo. METHODS: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide $<$40, 40, and $>$40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms. RESULTS: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on $<$40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking $>$40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow- up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization. CONCLUSIONS: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
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| 21. |
- Kristensen, S. L., et al.
(författare)
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Prevalence and incidence of intraventricular conduction delays and outcomes in patients with heart failure and reduced ejection fraction: Insights from PARADIGM-HF and ATMOSPHERE
- 2020
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 22:12, s. 2370-9
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The importance of intraventricular conduction delay (IVCD), incidence of new IVCD and its relationship to outcomes in heart failure and reduced ejection fraction (HFrEF) is not well studied. We addressed these questions in the PARADIGM-HF and ATMOSPHERE trials. METHODS AND RESULTS: Risk of the primary composite outcome of cardiovascular death or HF hospitalization and all-cause mortality were estimated by use of Cox regression according to baseline QRS duration and morphology in 11,861 patients without an intracardiac device. At baseline, 1,789 (15.1%) patients had left bundle branch block (LBBB), 524 (4.4%) RBBB, 454 (3.8%) non-specific IVCD, 2588 (21.8%) "mildly abnormal" QRS (110-129 milliseconds [ms]) and 6506 (54.9%) QRS <110 ms. During a median follow-up of 2.5 years, the risk of the primary composite endpoint was higher among those with a wide QRS, irrespective of morphology: hazard ratios (95% CI) LBBB 1.36 (1.23, 1.50), RBBB 1.54 (1.31, 1.79), nonspecific IVCD 1.65 (1.40, 1.94) and QRS 110-129 ms 1.35 (95% CI 1.23, 1.47), compared with QRS duration <110 ms. A total of 1,234 (15.6%) patients developed new-onset QRS-widening >/=130 ms (6.1 per 100 py). Incident LBBB occurred in 495 (6.3%) patients (2.4 per 100 py) and was associated with a higher risk of the primary composite outcome; HR 1.42 (1.12, 1.82). CONCLUSION: In patients with HFrEF, a wide QRS was associated with worse clinical outcomes irrespective of morphology. The annual incidence of new-onset LBBB was around 2.5%, and associated with a higher risk of adverse outcomes, highlighting the importance of repeat ECG review.
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| 22. |
- Petrie, Mark C, et al.
(författare)
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Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes.
- 2020
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 323:14, s. 1353-1368
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Tidskriftsartikel (refereegranskat)abstract
- Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes.To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes.Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019.Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy.The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%.Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (P value for interaction=.80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 [95% CI, 0.59-0.94]) (P value for interaction=.72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes.In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status.ClinicalTrials.gov Identifier: NCT03036124.
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| 23. |
- Serenelli, Matteo, et al.
(författare)
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Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).
- 2020
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 41:36, s. 3402-3418
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Tidskriftsartikel (refereegranskat)abstract
- Concern about hypotension often leads to withholding of beneficial therapy in patients with heart failure and reduced ejection fraction (HFrEF). We evaluated the efficacy and safety of dapagliflozin, which lowers systolic blood pressure (SBP),according to baseline SBP in Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).Key inclusion criteria were: New York Heart Association Class II-IV, left ventricular ejection fraction ≤ 40%, elevated N-terminal pro-B-type natriuretic peptide level, and SBP ≥95mmHg. The primary outcome was a composite of worsening heart failure or cardiovascular death. The efficacy and safety of dapagliflozin were examined using SBP as both a categorical and continuous variable. A total of 1205 patients had a baseline SBP <110mmHg; 981≥110<120; 1149≥120<130; and 1409≥130mmHg. The placebo-corrected reduction in SBP from baseline to 2weeks with dapagliflozin was -2.54 (-3.33 to -1.76) mmHg (P<0.001), with a smaller between-treatment difference in patients in the lowest compared to highest SBP category. Patients in the lowest SBP category had a much higher rate (per 100 person-years) of the primary outcome [20.6, 95% confidence interval (95% CI) 17.6-24.2] than those in the highest SBP category (13.8, 11.7-16.4). The benefit and safety of dapagliflozin was consistent across the range of SBP; hazard ratio (95% CI) in each SBP group, lowest to highest: 0.76 (0.60-0.97), 0.76 (0.57-1.02), 0.81 (0.61-1.08), and 0.67 (0.51-0.87), P interaction = 0.78. Study drug discontinuation did not differ between dapagliflozin and placebo across the SBP categories examined.Dapagliflozin had a small effect on SBP in patients with HFrEF and was superior to placebo in improving outcomes, and well tolerated, across the range of SBP included in DAPA-HF.ClinicalTrials.gov NCT03036124.
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