Insights on prevalence and incidence of anemia and rapid up-titration of oral heart failure treatment from the STRONG-HF study.

Anemia Guideline-directed medical therapy Heart failure

Journal

Clinical research in cardiology : official journal of the German Cardiac Society

ISSN: 1861-0692

Titre abrégé: Clin Res Cardiol

Pays: Germany

ID NLM: 101264123

Informations de publication

Date de publication:
11 Sep 2024

Historique:

received: 06 05 2024

accepted: 05 08 2024

medline: 11 9 2024

pubmed: 11 9 2024

entrez: 11 9 2024

Statut: aheadofprint

Résumé

Anemia is one of the most frequent comorbidities in patients with heart failure (HF), which potentially can interfere with the effect of guideline-recommended HF medical therapy and can be associated with the use of neurohormonal blockers. The aim of this analysis was to determine the prevalence and changes of anemia status in the STRONG-HF study, its association with clinical endpoints, and possible interaction of the presence of anemia with the efficacy and safety of high-intensity HF treatment. The design and main results of the study have been previously described. Patients were randomized within 2 days prior to anticipated hospital discharge after HF worsening in a 1:1 fashion to either high-intensity care (HIC) or usual care (UC). Baseline characteristics, clinical and safety outcomes, and treatment effect of HIC vs. UC on the primary and secondary outcomes were compared in groups based on baseline anemia. In addition, dynamics of hemoglobin during the study follow-up and predictors of incident anemia at 90 days were investigated. The proportion of anemia in 1077 STRONG-HF patients at enrollment was 27.2%, while at 90 days, it changed to 32.1%. The primary composite outcome occurred in 18.2% of patients without baseline anemia, and 22.5% of patients with baseline anemia (unadjusted HR 1.27; 95% CI 0.90-1.80), a difference that did not reach statistical significance. However, patients with baseline anemia had significantly less improvement of EQ-VAS questionnaire values from baseline to day 90 (adjusted LS-Mean difference -2.34 (-4.37, -0.31), P = 0.02). During the study, anemia developed in 19.4 and 14.6% in HIC and UC groups, respectively. The opposite phenomenon-recovery of anemia-occurred in 27.6 and 28.8% in HIC and UC groups (P = 0.1379). The predictors of incident anemia at 90 days were male sex, geographical region other than Europe, ischemic etiology, higher glucose, and elevated uric acid at baseline. The percentages of optimal doses of renin-angiotensin system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists were not different between anemic and non-anemic patients. High-intensity care strategy did not increase rate of incident anemia at 90 days and reduced the rate of primary and secondary endpoints regardless of baseline hemoglobin. Hemoglobin level and status of anemia have a dynamic nature in the acute HF patients in the post-discharge period dependent on multiple factors. High-intensity HF treatment is safe and beneficial regardless of baseline hemoglobin level and presence of anemia. The improvement of quality of life is significantly lower in anemic HF patients implying specific attention to correction of this condition.

Sections du résumé

BACKGROUND BACKGROUND

AIM OBJECTIVE

The aim of this analysis was to determine the prevalence and changes of anemia status in the STRONG-HF study, its association with clinical endpoints, and possible interaction of the presence of anemia with the efficacy and safety of high-intensity HF treatment.

METHODS METHODS

The design and main results of the study have been previously described. Patients were randomized within 2 days prior to anticipated hospital discharge after HF worsening in a 1:1 fashion to either high-intensity care (HIC) or usual care (UC). Baseline characteristics, clinical and safety outcomes, and treatment effect of HIC vs. UC on the primary and secondary outcomes were compared in groups based on baseline anemia. In addition, dynamics of hemoglobin during the study follow-up and predictors of incident anemia at 90 days were investigated.

RESULTS RESULTS

The proportion of anemia in 1077 STRONG-HF patients at enrollment was 27.2%, while at 90 days, it changed to 32.1%. The primary composite outcome occurred in 18.2% of patients without baseline anemia, and 22.5% of patients with baseline anemia (unadjusted HR 1.27; 95% CI 0.90-1.80), a difference that did not reach statistical significance. However, patients with baseline anemia had significantly less improvement of EQ-VAS questionnaire values from baseline to day 90 (adjusted LS-Mean difference -2.34 (-4.37, -0.31), P = 0.02). During the study, anemia developed in 19.4 and 14.6% in HIC and UC groups, respectively. The opposite phenomenon-recovery of anemia-occurred in 27.6 and 28.8% in HIC and UC groups (P = 0.1379). The predictors of incident anemia at 90 days were male sex, geographical region other than Europe, ischemic etiology, higher glucose, and elevated uric acid at baseline. The percentages of optimal doses of renin-angiotensin system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists were not different between anemic and non-anemic patients. High-intensity care strategy did not increase rate of incident anemia at 90 days and reduced the rate of primary and secondary endpoints regardless of baseline hemoglobin.

CONCLUSION CONCLUSIONS

Hemoglobin level and status of anemia have a dynamic nature in the acute HF patients in the post-discharge period dependent on multiple factors. High-intensity HF treatment is safe and beneficial regardless of baseline hemoglobin level and presence of anemia. The improvement of quality of life is significantly lower in anemic HF patients implying specific attention to correction of this condition.

Identifiants

DOI: 10.1007/s00392-024-02518-y PMID: 39259364

pubmed: 39259364

doi: 10.1007/s00392-024-02518-y

pii: 10.1007/s00392-024-02518-y

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Informations de copyright

Références

Mebazaa A, Davison B, Chioncel O, Cohen-Solal A, Diaz R, Filippatos G, Metra M, Ponikowski P, Sliwa K, Voors AA, Edwards C, Novosadova M, Takagi K, Damasceno A, Saidu H, Gayat E, Pang PS, Celutkiene J, Cotter G (2022) Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial. Lancet. https://doi.org/10.1016/S0140-6736(22)02076-1

doi: 10.1016/S0140-6736(22)02076-1 pubmed: 36356631

McDonagh TA, Metra M, Adamo M, Baumbach A, Böhm M, Burri H, Čelutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gardner RS, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Piepoli MF, Price S, Rosano GMC, Ruschitzka F, Skibelund AK, de Boer RA, Schulze PC, Abdelhamid M, Aboyans V, Adamopoulos S, Anker SD, Arbelo E, Asteggiano R, Bauersachs J, Bayes-Genis A, Borger MA, Budts W, Cikes M, Damman K, Delgado V, Dendale P, Dilaveris P, Drexel H, Ezekowitz J, Falk V, Fauchier L, Filippatos G, Fraser A, Frey N, Gale CP, Gustafsson F, Harris J, Iung B, Janssens S, Jessup M, Konradi A, Kotecha D, Lambrinou E, Lancellotti P, Landmesser U, Leclercq C, Lewis BS, Leyva F, Linhart A, Løchen ML, Lund LH, Mancini D, Masip J, Milicic D, Mueller C, Nef H, Nielsen JC, Neubeck L, Noutsias M, Petersen SE, Petronio AS, Ponikowski P, Prescott E, Rakisheva A, Richter D, Schlyakhto E, Seferovic P, Senni M, Sitges M, Sousa-Uva M, Tocchetti CG, Touyz R, Tschoepe C, Waltenberger J, Krim M, Hayrapetyan H, Moertl D, Mustafayev I, Kurlianskaya A, Depauw M, Kušljugić Z, Gatzov P, Agathangelou P, Melenovský V, Løgstrup BB, Mostafa AM, Uuetoa T, Lassus J, Logeart D, Kipiani Z, Chrysohoou C, Sepp R, Ingimarsdóttir IJ, O’Neill J, Gotsman I, Iacoviello M, Bajraktari G, Lunegova O, Kamzola G, Massih TA, Benlamin H, Žaliaduonyte D, Noppe S, Moore A, Vataman E, Boskovic A, Bennis A, Manintveld OC, Kostovska ES, Gulati G, Straburzyńska-Migaj E, Silva-Cardoso J, Rimbaş RC, Lopatin Y, Foscoli M, Stojkovic S, Goncalvesova E, Fras Z, Segovia J, Lindmark K, Maeder MT, Bsata W, Abid L, Altay H, Voronkov L, Davies C, Abdullaev T, Baigent CN, Antoniou S, Collet JP, Halvorsen S, Koskinas KC (2021) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 42:3599–3726. https://doi.org/10.1093/EURHEARTJ/EHAB368

doi: 10.1093/EURHEARTJ/EHAB368 pubmed: 34447992

McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Piepoli MF, Price S, Rosano GMC, Ruschitzka F, Skibelund AK, Group ESD, de Boer RA, Schulze PC, Arbelo E, Bartunek J, Bauersachs J, Borger MA, Buccheri S, Cerbai E, Donal E, Edelmann F, Färber G, Heidecker B, Ibanez B, James S, Køber L, Koskinas KC, Masip J, McEvoy JW, Mentz R, Mihaylova B, Møller JE, Mullens W, Neubeck L, Nielsen JC, Pasquet AA, Ponikowski P, Prescott E, Rakisheva A, Rocca B, Rossello X, Sade LE, Schaubroeck H, Tessitore E, Tokmakova M, van der Meer P, Van Gelder IC, Van Heetvelde M, Vrints C, Wilhelm M, Witkowski A, Zeppenfeld K, Shuka N, Chettibi M, Hayrapetyan H, Pavo N, Islamli A, Pouleur A-C, Kusljugic Z, Tokmakova M, Milicic D, Christodoulides T, Malek F, Køber L, Koriem MAG, Põder P, Lassus J, Roubille F, Agladze V, Frantz S, Stavrati A, Kosztin A, Ingimarsdóttir IJ, Campbell P, Hasin T, Oliva F, Aidargaliyeva N, Bajraktari G, Mirrakhimov E, Kamzola G, El Neihoum AM, Zaliaduonyte D, Moore A, Vataman E, Boskovic A, Alami M, Manintveld O, Kostovska ES, Broch K, Nessler J, Franco F, Popescu BA, Foscoli M, Milosavljevic AS, Goncalvesova E, Fras Z, Gonzalez-Costello J, Lindmark K, Paul M, Oudeh A, Zakhama L, Celik A, Voronkov L, Clark A, Abdullaev T, Prescott E, James S, Arbelo E, Baigent C, Borger MA, Buccheri S, Ibanez B, Køber L, Koskinas KC, McEvoy JW, Mihaylova B, Mindham R, Neubeck L, Nielsen JC, Pasquet AA, Rakisheva A, Rocca B, Rossello X, Vaartjes I, Vrints C, Witkowski A, Zeppenfeld K (2023) Eur Heart J 44:3627–3639. https://doi.org/10.1093/EURHEARTJ/EHAD195

doi: 10.1093/EURHEARTJ/EHAD195 pubmed: 37622666

Chioncel O, Davison B, Adamo M, Antohi LE, Arrigo M, Barros M, Biegus J, Čerlinskaitė-Bajorė K, Celutkiene J, Cohen-Solal A, Damasceno A, Diaz R, Edwards C, Filippatos G, Kimmoun A, Lam CSP, Metra M, Novosadova M, Pagnesi M, Pang PS, Ponikowski P, Radu RI, Saidu H, Sliwa K, Voors AA, Takagi K, Ter Maaten JM, Tomasoni D, Cotter G, Mebazaa A (2023) Non-cardiac comorbidities and intensive up-titration of oral treatment in patients recently hospitalized for heart failure: Insights from the STRONG-HF trial. Eur J Heart Fail 25:1994–2006. https://doi.org/10.1002/EJHF.3039

doi: 10.1002/EJHF.3039 pubmed: 37728038

Groenveld HF, Januzzi JL, Damman K, van Wijngaarden J, Hillege HL, van Veldhuisen DJ, van der Meer P (2008) Anemia and mortality in heart failure patients: a systematic review and meta-analysis. J Am Coll Cardiol 52:818–827. https://doi.org/10.1016/J.JACC.2008.04.061

doi: 10.1016/J.JACC.2008.04.061 pubmed: 18755344

Ishani A, Weinhandl E, Zhao Z, Gilbertson DT, Collins AJ, Yusuf S, Herzog CA (2005) Angiotensin-converting enzyme inhibitor as a risk factor for the development of anemia, and the impact of incident anemia on mortality in patients with left ventricular dysfunction. J Am Coll Cardiol 45:391–399. https://doi.org/10.1016/J.JACC.2004.10.038

doi: 10.1016/J.JACC.2004.10.038 pubmed: 15680718

Azizi M, Junot C, Ezan E, Ménard J (2001) Angiotensin I-converting enzyme and metabolism of the haematological peptide N-acetyl-seryl-aspartyl-lysyl-proline. Clin Exp Pharmacol Physiol 28:1066–1069. https://doi.org/10.1046/J.1440-1681.2001.03560.X

doi: 10.1046/J.1440-1681.2001.03560.X pubmed: 11903317

Komajda M, Anker SD, Charlesworth A, Okonko D, Metra M, Di Lenarda A, Remme W, Moullet C, Swedberg K, Cleland JGF, Poole-Wilson PA (2006) The impact of new onset anaemia on morbidity and mortality in chronic heart failure: results from COMET. Eur Heart J 27:1440–1446. https://doi.org/10.1093/EURHEARTJ/EHL012

doi: 10.1093/EURHEARTJ/EHL012 pubmed: 16717081

McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR (2014) PARADIGM-HF investigators and committees, angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 371:993–1004. https://doi.org/10.1056/NEJMoa1409077

doi: 10.1056/NEJMoa1409077 pubmed: 25176015

McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang C-E, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O’Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde A-M (2019) Dapagliflozin in patients with heart failure and reduced ejection fraction. Clinical Trial 381:1995–2008. https://doi.org/10.1056/NEJMOA1911303

doi: 10.1056/NEJMOA1911303

Streng KW, Nauta JF, Hillege HL, Anker SD, Cleland JG, Dickstein K, Filippatos G, Lang CC, Metra M, Ng LL, Ponikowski P, Samani NJ, van Veldhuisen DJ, Zwinderman AH, Zannad F, Damman K, van der Meer P, Voors AA (2018) Non-cardiac comorbidities in heart failure with reduced, mid-range and preserved ejection fraction. Int J Cardiol 271:132–139. https://doi.org/10.1016/J.IJCARD.2018.04.001

doi: 10.1016/J.IJCARD.2018.04.001 pubmed: 30482453

Chioncel O, Benson L, Crespo-Leiro MG, Anker SD, Coats AJS, Filippatos G, McDonagh T, Margineanu C, Mebazaa A, Metra M, Piepoli MF, Adamo M, Rosano GMC, Ruschitzka F, Savarese G, Seferovic P, Volterrani M, Ferrari R, Maggioni AP, Lund LH (2023) Comprehensive characterization of non-cardiac comorbidities in acute heart failure: an analysis of ESC-HFA EURObservational Research Programme Heart Failure Long-Term Registry. Eur J Prev Cardiol 30:1346–1358. https://doi.org/10.1093/EURJPC/ZWAD151

doi: 10.1093/EURJPC/ZWAD151 pubmed: 37172316

Fox MT, Jorde UP (2005) Anemia, chronic heart failure, and the impact of male vs female gender. Congest Heart Fail 11:129–132. https://doi.org/10.1111/J.1527-5299.2005.03953.X

doi: 10.1111/J.1527-5299.2005.03953.X pubmed: 15947533

Go AS, Yang J, Ackerson LM, Lepper K, Robbins S, Massie BM, Shlipak MG (2006) Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure. Circulation 113:2713–2723. https://doi.org/10.1161/CIRCULATIONAHA.105.577577

doi: 10.1161/CIRCULATIONAHA.105.577577 pubmed: 16754803

Mehdi U, Toto RD (2009) Anemia, diabetes, and chronic kidney disease. Diabetes Care 32:1320–1326. https://doi.org/10.2337/DC08-0779

doi: 10.2337/DC08-0779 pubmed: 19564475 pmcid: 2699743

Shah R, Agarwal AK (2013) Anemia associated with chronic heart failure: current concepts. Clin Interv Aging 8:111. https://doi.org/10.2147/CIA.S27105

doi: 10.2147/CIA.S27105 pubmed: 23403618 pmcid: 3569049

Van Der Meer P, Lipsic E, Westenbrink BD, Van De Wal RMA, Schoemaker RG, Vellenga E, Van Veldhuisen DJ, Voors AA, Van Gilst WH (2005) Levels of hematopoiesis inhibitor N-acetyl-seryl-aspartyl-lysyl-proline partially explain the occurrence of anemia in heart failure. Circulation 112:1743–1747. https://doi.org/10.1161/CIRCULATIONAHA.105.549121

doi: 10.1161/CIRCULATIONAHA.105.549121 pubmed: 16172283

Anand IS, Kuskowski MA, Rector TS, Florea VG, Glazer RD, Hester A, Chiang YT, Aknay N, Maggioni AP, Opasich C, Latini R, Cohn JN (2005) Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure. Circulation 112:1121–1127. https://doi.org/10.1161/CIRCULATIONAHA.104.512988

doi: 10.1161/CIRCULATIONAHA.104.512988 pubmed: 16103233

Guralnik JM, Ershler WB, Schrier SL, Picozzi VJ (2005) Anemia in the elderly: a public health crisis in hematology. Hematology 2005:528–532. https://doi.org/10.1182/ASHEDUCATION-2005.1.528

doi: 10.1182/ASHEDUCATION-2005.1.528

Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC (2004) Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood 104:2263–2268. https://doi.org/10.1182/BLOOD-2004-05-1812

doi: 10.1182/BLOOD-2004-05-1812 pubmed: 15238427

Mansoor F, Bai P, Kaur N, Sultan S, Sharma S, Dilip A, Kammawal Y, Shahid S, Rizwan A (2021) Evaluation of serum electrolyte levels in patients with anemia. Cureus. https://doi.org/10.7759/CUREUS.18417

doi: 10.7759/CUREUS.18417 pubmed: 35111481 pmcid: 8794366

Rafiq M, Arooj A, Tahir Q-A, Fayyaz N, Samad A, Bashir S (2021) Evaluation of serum electrolyte levels in iron deficiency anemia patients. Prof Med J 28:691–696. https://doi.org/10.29309/TPMJ/2021.28.05.5702

doi: 10.29309/TPMJ/2021.28.05.5702

Balducci L, Hardy CL, Lyman GH (2000) Hemopoietic reserve in the older cancer patient. Clin Econ Consid 7:539–547. https://doi.org/10.1177/107327480000700605

doi: 10.1177/107327480000700605