Guideline-Directed Heart Failure Pharmacotherapy in Adults Aged ≥75 Years: Evidence Gaps, Tolerability, and Implications for Clinical Practice

Maggioni AP, Anker SD, Dahlström U, Filippatos G, Ponikowski P, Zannad F, et al. Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12,440 patients of the ESC Heart Failure Long-Term Registry. Eur J Heart Fail. 2013;15(10):1173–84. https://doi.org/10.1093/eurjhf/hft134.

Article  CAS  PubMed  Google Scholar 

Chioncel O, Lainscak M, Seferovic PM, Anker SD, Crespo-Leiro MG, Harjola VP, et al. Epidemiology and one-year outcomes in patients with chronic heart failure and preserved, mid-range and reduced ejection fraction: an analysis of the ESC Heart Failure Long-Term Registry. Eur J Heart Fail. 2017;19(12):1574–85. https://doi.org/10.1002/ejhf.813.

Article  CAS  PubMed  Google Scholar 

McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023;44(37):3627–39. https://doi.org/10.1093/eurheartj/ehad195. (Erratum in: Eur Heart J. 2024 Jan 1;45(1):53. doi: 10.1093/eurheartj/ehad613.).

Article  CAS  PubMed  Google Scholar 

Crespo-Leiro MG, Anker SD, Maggioni AP, Coats AJ, Filippatos G, Ruschitzka F, et al. European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT): 1-year follow-up outcomes and differences across regions. Eur J Heart Fail. 2016;18(6):613–25. https://doi.org/10.1002/ejhf.566.

Article  PubMed  Google Scholar 

Conrad N, Judge A, Tran J, Mohseni H, Hedgecott D, Crespillo AP, et al. Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals. Lancet. 2018;391(10120):572–80. https://doi.org/10.1016/S0140-6736(17)32520-5.

Article  PubMed  Google Scholar 

Savarese G, Lund LH. Global public health burden of heart failure. Card Fail Rev. 2017;3(1):7–11. https://doi.org/10.15420/cfr.2016:25:2.

Article  PubMed  PubMed Central  Google Scholar 

Shah KS, Xu H, Matsouaka RA, Bhatt DL, Heidenreich PA, Hernandez AF, et al. Heart failure with preserved, borderline, and reduced ejection fraction: 5-year outcomes. J Am Coll Cardiol. 2017;70(20):2476–86. https://doi.org/10.1016/j.jacc.2017.08.074.

Article  PubMed  Google Scholar 

CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med. 1987;316(23):1429–35. https://doi.org/10.1056/NEJM198706043162301.

Article  Google Scholar 

SOLVD Investigators, Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325(5):293–302. https://doi.org/10.1056/NEJM199108013250501.

Article  Google Scholar 

The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353(9146):9–13.

Effect of metoprolol CR/XL in chronic heart failure. Metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF). Lancet. 1999;353(9169):2001–7.

Article  Google Scholar 

Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341(10):709–17. https://doi.org/10.1056/NEJM199909023411001.

Article  CAS  PubMed  Google Scholar 

Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11–21. https://doi.org/10.1056/NEJMoa1009492.

Article  CAS  PubMed  Google Scholar 

McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993–1004. https://doi.org/10.1056/NEJMoa1409077.

Article  CAS  PubMed  Google Scholar 

McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995–2008. https://doi.org/10.1056/NEJMoa1911303.

Article  CAS  PubMed  Google Scholar 

Böhm M, Swedberg K, Komajda M, Borer JS, Ford I, Dubost-Brama A, et al. Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet. 2010;376(9744):886–94. https://doi.org/10.1016/S0140-6736(10)61259-7.

Article  PubMed  Google Scholar 

Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003;362(9386):759–66. https://doi.org/10.1016/s0140-6736(03)14282-1.

Article  CAS  PubMed  Google Scholar 

Tan E, Meei-Wah C, Teo YH, Tan LF, Ho VWT, Lin W, et al. Survival benefit of guideline-directed medical therapy in older patients with heart failure: a systematic review and meta-analysis. Heart. 2026. https://doi.org/10.1136/heartjnl-2025-326305.

Article  PubMed  PubMed Central  Google Scholar 

Nijskens CM, Handoko L, Remmelzwaal S, Ziesemer KA, Muller M. Efficacy and safety of heart failure treatment according to frailty status: a systematic review. J Am Heart Assoc. 2025;14(17):e042367. https://doi.org/10.1161/JAHA.125.042367.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Duong MH, Gnjidic D, McLachlan AJ, Redston MR, Goyal P, Mathieson S, et al. The effect of down-titration and discontinuation of heart failure pharmacotherapy in older people: a systematic review and meta-analysis. Br J Clin Pharmacol. 2025;91(1):23–37. https://doi.org/10.1111/bcp.16223.

Article  PubMed  Google Scholar 

Duong MH, Gnjidic D, McLachlan AJ, Sakiris MA, Goyal P, Hilmer SN. The prevalence of adverse drug reactions and adverse drug events from heart failure medications in frail older adults: a systematic review. Drugs Aging. 2022;39(8):631–43. https://doi.org/10.1007/s40266-022-00957-8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413–24. https://doi.org/10.1056/NEJMoa2022190.

Article  CAS  PubMed  Google Scholar 

Niederseer D, Thaler CW, Niederseer M, Niebauer J. Mismatch between heart failure patients in clinical trials and the real world. Int J Cardiol. 2013;168(3):1859–65. https://doi.org/10.1016/j.ijcard.2012.12.069.

Article  PubMed  Google Scholar 

Tahhan AS, Vaduganathan M, Greene SJ, Fonarow GC, Fiuzat M, Jessup M, et al. Enrollment of older patients, women, and racial and ethnic minorities in contemporary heart failure clinical trials: a systematic review. JAMA Cardiol. 2018;3(10):1011–9. https://doi.org/10.1001/jamacardio.2018.2559.

Article  PubMed  Google Scholar 

Mebazaa A, Davison B, Chioncel O, Cohen-Solal A, Diaz R, Filippatos G, et al. 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. 2022;400(10367):1938–52. https://doi.org/10.1016/S0140-6736(22)02076-1.

Article  CAS  PubMed  Google Scholar 

Stolfo D, Savarese G. Use of renin-angiotensin-aldosterone system inhibitors in older patients with heart failure and reduced ejection fraction. Card Fail Rev. 2019;5(2):70–3. https://doi.org/10.15420/cfr.2019.6.2.

Article  PubMed  PubMed Central  Google Scholar 

Brunner-La Rocca HP, Buser PT, Schindler R, Bernheim A, Rickenbacher P, et al. Management of elderly patients with congestive heart failure–design of the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF). Am Heart J. 2006;151(5):949–55. https://doi.org/10.1016/j.ahj.2005.10.022.

Article  PubMed  Google Scholar 

Jhund PS, Fu M, Bayram E, Chen CH, Negrusz-Kawecka M, Rosenthal A, et al. Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: insights from PARADIGM-HF. Eur Heart J. 2015;36(38):2576–84. https://doi.org/10.1093/eurheartj/ehv330.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca MP, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019;393(10166):31–9. https://doi.org/10.1016/S0140-6736(18)32590-X.

Article  CAS 

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