Rationale and design of the FAIR‐HF2‐DZHK05 trial: Ferric carboxymaltose assessment of morbidity and mortality in patients with iron deficiency and chronic heart failure

European Journal of Heart Failure, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Abstract Aims While it is widely accepted that intravenous (IV) iron improves functional capacity, symptoms, and cardiovascular outcomes in patients with heart failure (HF) reduced ejection fraction (HFrEF) diagnosed deficiency (ID), three recently published outcome trials (AFFIRM‐AHF, IRONMAN HEART‐FID) of IV supplementation HF failed to demonstrate a significant benefit on their respective primary endpoints. Dosing after the initial correction baseline ID – by design or as result trial circumstances was relatively low (i.e. <500 mg/year). The objective FAIR‐HF2 evaluate treatment effect ferric carboxymaltose (FCM) compared placebo ambulatory HFrEF using higher dose during follow‐up >1000 second study create prospective evidence for fulfilling new definition HF, i.e. those transferrin saturation <20%. Methods an investigator‐initiated, multicentre, randomized, double‐blind, placebo‐controlled has recruited 1105 chronic left ventricular ≤45% concomitant ID, defined serum ferritin <100 ng/ml 100–299 Patients were consented randomized receive either FCM (treatment) saline (placebo). During estimated median over 2 years, underwent repletion maintenance phase, up 2000 mg, followed 500 mg every 4 months unless stop criteria haemoglobin >16 mg/dl >800 are met repeat visits. will hypotheses: (i) time first event death hospitalization (ii) rate total (first recurrent) hospitalizations (both analysed full population), (iii) <20% at baseline. familywise type I error across endpoint hypotheses be controlled Hochberg procedure (alpha 0.05). Conclusion efficacy improving utilizing more aggressive approach towards ensuring prevention transitional targets have been met.

Language: Английский

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Intravenous iron and SGLT2 inhibitors in iron‐deficient patients with heart failure and reduced ejection fraction

ESC Heart Failure, Journal Year: 2024, Volume and Issue: 11(4), P. 1875 - 1879

Published: March 28, 2024

To explore the potential interaction between use of SGLT2 inhibitors and increase in haemoglobin patients randomized to intravenous iron or control group IRONMAN (Effectiveness Intravenous Iron Treatment versus Standard Care Patients with Heart Failure Deficiency) trial.

Language: Английский

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Treating iron deficiency in patients with heart failure: what, why, when, how, where and who

Heart, Journal Year: 2024, Volume and Issue: 110(20), P. 1201 - 1207

Published: Aug. 19, 2024

For patients with heart failure and reduced or mildly left ventricular ejection fraction, iron deficiency is common associated more severe symptoms, worse quality of life an increased risk hospitalisations death. Iron can be swiftly, effectively safely treated by administering intravenous iron, either as ferric carboxymaltose derisomaltose, which improves patient well-being reduces the including those for failure. However, current definition in has serious flaws. A serum ferritin <100 µg/L does not identify likely to respond iron. In contrast, transferrin saturations <20%, most whom are also anaemic, have a beneficial response this review, we summarise available evidence use provide recommendations targeted future research practical considerations general cardiologist.

Language: Английский

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SGLT2 Inhibitors and How They Work Beyond the Glucosuric Effect. State of the Art

American Journal of Cardiovascular Drugs, Journal Year: 2024, Volume and Issue: 24(6), P. 707 - 718

Published: Aug. 24, 2024

Language: Английский

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Ferric carboxymaltose assessment of morbidity and mortality in patients with iron deficiency and chronic heart failure (FAIR‐HF2‐DZHK05) trial: Baseline characteristics and comparison to other relevant clinical trials

European Journal of Heart Failure, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Aims Prior randomized trials have reported conflicting evidence regarding the efficacy of intravenous (IV) iron in patients with heart failure reduced ejection fraction (HFrEF) and deficiency (ID). Methods results FAIR‐HF2 is a double‐blind, randomized, controlled trial evaluating IV ferric carboxymaltose HFrEF ID. We report baseline characteristics enrolled compare them other major (FAIR‐HF, CONFIRM‐HF, AFFIRM‐AHF, IRONMAN, HEART‐FID). A total 1105 were between March 2017 November 2023. Most men (67%) median age was 72 (interquartile range [IQR] 63–79) years. More than one‐third had hospitalization within preceding 12 months (36%), 53% hospitalized at randomization. Common comorbidities included hypertension (79%), coronary artery disease (74%), dyslipidaemia (67%), diabetes (46%). The left ventricular 58% (IQR 42–77) mean estimated glomerular filtration rate 58 ml/min/1.73 m 2 . 1064 (96%) on renin–angiotensin system inhibitors (angiotensin receptor–neprilysin [ARNI] 38%), 1016 (92%) beta‐blockers, 779 (71%) mineralocorticoid receptor antagonists; 261 (24%) sodium–glucose cotransporter (SGLT2) inhibitors, which much higher prior trials. proportion ischaemic (78%) compared to haemoglobin (g/dl) 12.7 11.8–13.4), serum ferritin (μg/dl) 63 36–90), transferrin saturation (%) 16.5 11.8–22.9), resembling that 6‐min walk distance enrolment 314 ± 118 m. Conclusion represents contemporary cohort mostly similar populations. Use SGLT2 ARNI Clinical Trial Registration: ClinicalTrials.gov ID NCT03036462.

Language: Английский

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Translating evidence into practice: Managing electrolyte imbalances and iron deficiency in heart failure

European Journal of Internal Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

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Sodium-Glucose Cotransporter-2 Inhibitors in Diabetic Patients with Heart Failure: An Update

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(11), P. 1419 - 1419

Published: Oct. 23, 2024

Diabetes mellitus and heart failure are two diseases that commonly found together, in particular older patients. High blood glucose has a detrimental effect on the cardiovascular system, worse glycemic control contributes to onset recrudesce of failure. Therefore, any specific treatment aimed reduce glycated hemoglobin may, turn, have beneficial Sodium-glucose cotransporter-2 inhibitors been initially developed for type 2 diabetes mellitus, their significant action is increase glycosuria, which turn causes reduction level risk. However, recent clinical trials progressively demonstrated glycosuric sodium-glucose also diuretic effect, crucial target management patients with Additional studies documented improve therapeutical failure, independently by and, therefore, presence mellitus. In this review, we analyzed demonstrating efficacy treating chronic acute

Language: Английский

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Administration of ferric derisomaltose for iron deficiency and heart failure during hospital admission or at the clinic – insights from the IRONMAN trial

European Journal of Heart Failure, Journal Year: 2024, Volume and Issue: 26(10), P. 2293 - 2295

Published: July 30, 2024

Large clinical trials of intravenous iron for patients with heart failure have studied hospitalized immediately prior to discharge (AFFIRM-HF) and outpatients (HEART-FID)1-3; efficacy might differ by enrolment setting. IRONMAN (NCT02642562) was a prospective, randomized, open-label, blinded-endpoint trial comparing ferric derisomaltose (FDI) usual care in left ventricular ejection fraction (LVEF) ≤45% either serum ferritin <100 μg/L or transferrin saturation (TSAT) <20%.4-6 Patients were grouped according recruitment settings: (i) hospitalized; (ii) recently (within 6 months); (iii) without recent hospitalization elevated plasma concentrations natriuretic peptides. The primary outcome (HFH) (recurrent events) cardiovascular (CV) death. Secondary outcomes included: HFH (first event) CV death; myocardial infarction, stroke, (iv) all-cause hospitalization; (v) (vi) (vii) unplanned (viii) infection. In this pre-specified subgroup analysis, the effect FDI on secondary endpoints compared investigated Of 1137 164 enrolled hospital, 208 had been hospitalized, 765 more stable outpatients. median follow-up duration 2.7 years. hospital lowest haemoglobin other groups (median 11.5 vs. 12.0 12.3 g/dL), TSAT (medians 10% 14% 16%), highest proportion <20% (90% 76% 73%), 65 50 47 μg/L), estimated glomerular filtration rate (eGFR) 45 48 53 mL/min/1.73 m2), systolic blood pressure 113 117 121 mmHg), LVEF 30% 32% 35%), least likely ischaemic aetiology (41% 51% 62%), acute coronary syndrome (37% 42% 56%), worst (highest) Minnesota Living Heart Failure Questionnaire (MLHFQ) scores (physical score 30 24 22). Other baseline characteristics, including age sex similar across groups. loop diuretics less renin–angiotensin system inhibitors (angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, sacubitril/valsartan) at baseline. Similar proportions beta-blockers, mineralocorticoid antagonists, sodium–glucose cotransporter 2 (SGLT2) inhibitors, digoxin. Investigators encouraged optimize treatment per international practice guidelines all visits7; therefore, treatments may changed over follow-up. arm double (rate/100 patient-years 44 group 22 outpatient group). similar, terms relative risk, irrespective setting (Figure 1). change from month 4 consistent different settings (pinteraction = 0.16). Enrolment associated greater MLHFQ physical months (difference [95% confidence interval] −3 [−5, −1]) (−2 [−6, 2]) (2 [−2, 5]) 0.043). is first provide within-trial comparisons As anticipated, higher risk profile generally demonstrated rates endpoints. benefits, terms, between regardless whether initiated inpatient suggest that therapy be beneficial broad range throughout their disease trajectory. Hospital admission provides an opportune window optimizing medical therapy, correction deficiency. Indeed, if benefits are same profile, absolute benefit will amongst risk. Compared those settings, features severe (including lower eGFR, pressure, LVEF) which itself underpin haemoglobin. Haemodilution also contribute. Lower TSAT, indicating worse deficiency, reflect severity inflammation, potentially contributing Higher levels seen inflammation due various causes. AFFIRM-AHF, given discharge; it challenging coordinate this. contrast, IRONMAN, could receive any time during stay, allows resources used flexibly, helping mitigate 'therapeutic inertia' potential delays initiation. Reassuringly, there no suggestion increased infection increase hazards settings. difference three SGLT2 foundational failure, necessitating understanding interactions iron. post-hoc analysis trend towards iron-deficient not one.8 This has several limitations should acknowledged. powered investigate effects subgroups. Patient characteristics differed many ways context, account observed trends lack thereof. solely UK, most White men, therefore results extrapolated populations caution. conclusion, exhibited outpatients, but reduction wards clinics. These findings offer breadth management failure. We thank Public Health Scotland NHS Digital provision data linkage. participants, physicians, nurses, staff who contributed study. study funded British Foundation (grant award CS/15/1/31175) Pharmacosmos. Pharmacosmos provided supplies supported additional unrestricted grant. M.C.P. Centre Research Excellence Award (RE/13/5/30177 RE/18/6/34217). Conflict interest: none declared.

Language: Английский

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Therapeutic Consequences and Prognostic Impact of Multimorbidity in Heart Failure: Time to Act

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 14(1), P. 139 - 139

Published: Dec. 29, 2024

Background/Objectives: In heart failure (HF) with reduced ejection fraction (HFrEF), the early diagnosis and proper treatment of comorbidities (CMs) are fundamental relevance. Our aim was to assess prevalence CMs among real-world patients requiring hospitalisation for HFrEF investigate effect on implementation guideline-directed medical therapy (GDMT) all-cause mortality (ACM). Methods: The data a consecutive patient cohort hospitalised HF between 2021 2024 were analysed retrospectively. Sixteen (6 CV 10 non-CV) considered. Patients divided into three categories: 0–3 vs. 4–6 ≥7 CMs. GDMT at discharge ACM compared CM categories. predictors 1-year also evaluated. Results: From 388 (male: 76%, age: 61 [50–70] years; NT-proBNP: 5286 [2570–9923] pg/mL; ≥2 cardiovascular–kidney–metabolic disease overlap: 46%), large proportion received (RASi: 91%; βB: 85%; MRA: 95%; SGLT2i: 59%; triple [TT: RASi+βB+MRA]: 82%; quadruple [QT: TT + SGLT2i]: 54%) discharge. Multimorbidity accompanied (p < 0.05) lower application ratio RASi (96% 92% CMs) βB (94% 85% 78%), while MRA (99% 94% 94%) SGTL2i use (61% 59% 57%) did not differ > 0.05). multimorbidity less likely be treated (93% 82% 73%, p = 0.001), no difference detected in QT (56% 54% 50%, 0.685). an increased burden higher (9% 13% 25%, 0.003). risk favourably affected by TT/QT severe left ventricular systolic dysfunction, having ≥5 had unfavourable impact prognosis. Conclusions: According our analysis, can expect favourable outcome. However, modern even applied this population, resulting significantly improved Thus, clinicians should insist early, conscious prognosis-modifying drug regime multimorbid as well.

Language: Английский

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