In this double-blind trial, patients with chronic kidney disease and type 2 diabetes were randomly assigned to receive the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone or ...placebo. Treatment with finerenone resulted in lower risks of chronic kidney disease outcomes and cardiovascular outcomes than placebo.
Patients with acute heart failure who received ularitide had greater reductions in systolic blood pressure and in levels of N-terminal pro–brain natriuretic peptide than those receiving placebo but ...had no improvement in cardiovascular mortality.
Acute presentation with new-onset heart failure and rapid worsening of preexisting heart failure are two of the most common causes of hospitalization worldwide.
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The disorder in each case is characterized by intravascular volume expansion and ventricular distention, which may cause myocardial injury in the absence of coronary artery disease or occlusion.
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Episodes are associated with an accelerated rate of disease progression; each hospitalization for heart failure increases the risk of subsequent admissions as well as the risk of death from cardiovascular causes.
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The first few hours after the initial presentation with acute heart failure may represent a period of . . .
Aims
To evaluate the impact of physicians' adherence to guideline‐recommended medications for heart failure with reduced ejection fraction (HFrEF), including ≥50% prescription of recommended doses, ...on clinical outcomes at 6‐month follow‐up.
Methods and results
In QUALIFY, an international, prospective, observational, longitudinal survey, 6669 outpatients with HFrEF were recruited 1–15 months after heart failure (HF) hospitalization from September 2013 to December 2014 in 36 countries and followed up at 6 months. A global adherence to guidelines score was developed for prescription of angiotensin‐converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta‐blockers (BBs), mineralocorticoid receptor antagonists (MRAs) and ivabradine and their dosages. Baseline global adherence score was good in 23% of patients, moderate in 55%, and poor in 22%. At 6‐month follow‐up, poor adherence was associated with significantly higher overall mortality hazard ratio (HR) 2.21, 95% confidence interval (CI) 1.42–3.44, P=0.001, cardiovascular mortality (HR 2.27, 95% CI 1.36–3.77, P=0.003), HF mortality (HR 2.26, 95% CI 1.21–4.2, P=0.032), combined HF hospitalization or HF death (HR 1.26, 95% CI 1.08–1.71, P=0.024) and cardiovascular hospitalization or cardiovascular death (HR 1.35, 95% CI 1.08–1.69, P=0.013). There was a strong trend between poor adherence and HF hospitalization (HR 1.32, 95% CI 1.04–1.68, P=0.069).
Conclusion
Good adherence to pharmacologic treatment guidelines for ACEIs, ARBs, BBs, MRAs and ivabradine, with prescription of at least 50% of recommended dosages, was associated with better clinical outcomes during 6‐month follow‐up. Continuing global educational initiatives are needed to emphasise the importance of guideline recommendations for optimising drug therapy and prescribing evidence‐based doses in clinical practice.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Aims
To assess physicians' adherence to guideline‐recommended medications for the treatment of chronic heart failure (CHF) with reduced ejection fraction.
Methods and results
QUALIFY is an ...international prospective observational longitudinal survey of 7092 CHF outpatients recruited 1–15 months after hospitalization for heart failure from September 2013 to December 2014 in 547 centres in 36 countries. We constructed a five‐class guideline adherence score for angiotensin converting enzyme inhibitors (ACEIs), beta‐blockers, angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists, and ivabradine. The adherence score was good in 67%, moderate in 25%, and poor in 8% of patients. Adherence was lower in women than men but there were differences in age (65.7 ± 12.5 years women vs. 62.2 ± 12.4 years men, P < 0.001) and the proportion of women at ≥50% target dose of beta‐blockers was lower in those >67 years (median) (11% vs. 16.2%, P = 0.005). Geographic variations were observed with lower adherence scores in Central/Eastern European countries. The proportion of patients at target dose and ≥50% of target dose was low (27.9% and 63.3% for ACEIs, 14.8% and 51.8% for beta‐blockers, 6.9% and 39.5% for ARBs, and 6.9% and 39.5% for ivabradine, respectively). It was also lower in patients most recently hospitalized (<6 vs. ≥6 months) except for beta‐blockers.
Conclusion
This international survey shows that adherence to guideline‐recommended medications is relatively satisfactory but the dosage of recommended CHF medications is usually suboptimal. Action plans aimed at improving adherence to guidelines are required.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Among patients with heart failure and a reduced ejection fraction, those who received the SGLT2 inhibitor empagliflozin had a significantly lower incidence of cardiovascular death or hospitalization ...for heart failure than those who received placebo.
Aims
Inflammation is a central process in the pathophysiology of heart failure (HF), but trials targeting tumour necrosis factor (TNF)‐α were largely unsuccessful. Interleukin (IL)‐6 is an important ...inflammatory mediator and might constitute a potential pharmacologic target in HF. However, little is known regarding the association between IL‐6 and clinical characteristics, outcomes and other inflammatory biomarkers in HF. We thus aimed to identify and characterize these associations.
Methods and results
Interleukin‐6 was measured in 2329 patients 89.4% with a left ventricular ejection fraction (LVEF) ≤ 40% of the BIOSTAT‐CHF cohort. The primary outcome was all‐cause mortality and HF hospitalization during 2 years, with all‐cause, cardiovascular (CV), and non‐CV death as secondary outcomes. Approximately half (56%) of all included patients had plasma IL‐6 values greater than the previously determined 95th percentile of normal values at baseline. Elevated N‐terminal pro‐brain natriuretic peptide, procalcitonin and hepcidin, younger age, TNF‐α/IL‐1‐related biomarkers, or having iron deficiency, atrial fibrillation and LVEF > 40% independently predicted elevated IL‐6 levels. IL‐6 independently predicted the primary outcome HR (95% confidence interval) per doubling: 1.16 (1.11–1.21), P < 0.001, all‐cause mortality 1.22 (1.16–1.29), P < 0.001 and CV as well as non‐CV mortality 1.16 (1.09–1.24), P < 0.001; 1.31 (1.18–1.45), P < 0.001, but did not improve discrimination in previously published risk models.
Conclusions
In a large, heterogeneous cohort of HF patients, elevated IL‐6 levels were found in more than 50% of patients and were associated with iron deficiency, reduced LVEF, atrial fibrillation and poorer clinical outcomes. These findings warrant further investigation of IL‐6 as a potential therapeutic target in specific HF subpopulations.
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Table of Contents Preamble777 Introduction779 Methodology and Evidence Review779 Organization of the Writing Group779 Document Review and Approval779 Initial and Serial Evaluation of the HF ...Patient780 Biomarkers780 Biomarkers for Prevention: Recommendation781 Biomarkers for Diagnosis: Recommendation782 Biomarkers for Prognosis or Added Risk Stratification: Recommendations782 Treatment of Stages A to D784 Stage C784 Pharmacological Treatment for Stage C HF With Reduced Ejection Fraction: Recommendations784 Renin-Angiotensin System Inhibition With Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker or ARNI: Recommendation791 Treating Hypertension in Stage C HFrEF: Recommendation791 Treating Hypertension in Stage C HFpEF: Recommendation791 Sleep-Disordered Breathing: Recommendations792 References793 Appendix 1 Author Relationships With Industry and Other Entities (Relevant)798 Appendix 2 Reviewer Relationships With Industry and Other Entities (Comprehensive)800 Appendix 3 Abbreviations803 Preamble Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health. Effects of more vs. less intensive blood pressure lowering and different achieved blood pressure levels - updated overview and meta-analyses of randomized trials, J Hypertens, Vol. 34, 2016, 613-622 191 J.T. Wright Jr., J.D. Williamson, P.K. Whelton, A Randomized Trial of Intensive versus Standard Blood-Pressure Control, N Engl J Med, Vol. 373, 2015, 2103-2116 192 J.D. Williamson, M.A. Supiano, W.B. Applegate, JAMA, Vol. 315, 2016, 2673-2682 193 J. Lv, P. Ehteshami, M.J. Sarnak, Effects of intensive blood pressure lowering on the progression of chronic kidney disease: a systematic review and meta-analysis, CMAJ, Vol. 185, 2013, 949-957 194 Deleted in press. 195 W.S. Aronow, J.L...
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Drugs that inhibit the sodium–glucose co‐transporter 2 (SGLT2) have been shown to reduce the risk of hospitalizations for heart failure in patients with type 2 diabetes. In populations that largely ...did not have heart failure at the time of enrolment, empagliflozin, canagliflozin and dapagliflozin decreased the risk of serious new‐onset heart failure events by ≈30%. In addition, in the EMPA‐REG OUTCOME trial, empagliflozin reduced the risk of both pump failure and sudden deaths, the two most common modes of death among patients with heart failure. In none of the three trials could the benefits of SGLT2 inhibitors on heart failure be explained by the actions of these drugs as diuretics or anti‐hyperglycaemic agents. These observations raise the possibility that SGLT2 inhibitors could reduce morbidity and mortality in patients with established heart failure, including those without diabetes. The EMPEROR‐Reduced trial is enrolling ≈3600 patients with heart failure and a reduced left ventricular ejection fraction (≤ 40%), half of whom are expected not to have diabetes. Patients are being randomized to placebo or empagliflozin 10 mg daily, which is added to all appropriate treatment with inhibitors of the renin–angiotensin system and neprilysin, beta‐blockers and mineralocorticoid receptor antagonists. The primary endpoint is the time‐to‐first event analysis of the combined risk of cardiovascular death and hospitalization for heart failure, but the trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death, all‐cause mortality, and recurrent hospitalization events. By adjusting eligibility based on natriuretic peptide levels to the baseline ejection fraction, the trial will preferentially enrol high‐risk patients. A large proportion of the participants is expected to have an ejection fraction < 30%, and the estimated annual event rate is expected to be at least 15%. The EMPEROR‐Reduced trial is well‐positioned to determine if the addition of empagliflozin can add meaningfully to current approaches that have established benefits in the treatment of chronic heart failure with left ventricular systolic dysfunction.
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