Sacubitril-valsartan in Patients With Heart Failure With Reduced Ejection Fraction From Rural Tanzania

Summary

Angiotensin-neprilysin inhibitors (ARNI) are beneficial in patients with heart failure with reduced ejection fraction. No study evaluating ARNI has been conducted in sub-Saharan Africa (except South Africa) yet, where heart failure is a major health problem. Before implementing ARNI in Tanzania, a study evaluating the benefit and safety of ARNI in Africans is needed. The aim of this interventional pre-post study is to evaluate the health status of symptomatic patients with heart failure with reduced ejection fraction who are under a chronic heart failure therapy, before and after switching angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) to ARNI. Participants will be recruited at the Heart and Lung Clinic of the St Francis Regional Referral Hospital in Ifakara in rural Tanzania during a study period of 30 months, including 10 months of follow-up. A total of 298 participants will be included. The investigators hypothesize that health status, expressed by the Kansas City Cardiomyopathy Questionnaire summary score and 6-minute walking test, will improve after switching from ACE-inhibitors or ARB to ARNI. In Tanzania, sacubitril/valsartan is registered under the name Uperio®.

Timeline

Start

2026-06-30

Primary completion

2028-11-30

Completion

2028-11-30

Publications

• Results Senni M, McMurray JJ, Wachter R, McIntyre HF, Reyes A, Majercak I, Andreka P, Shehova-Yankova N, Anand I, Yilmaz MB, Gogia H, Martinez-Selles M, Fischer S, Zilahi Z, Cosmi F, Gelev V, Galve E, Gomez-Doblas JJ, Nociar J, Radomska M, Sokolova B, Volterrani M, Sarkar A, Reimund B, Chen F, Charney A. Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens. Eur J Heart Fail. 2016 Sep;18(9):1193-202. doi: 10.1002/ejhf.548. Epub 2016 May 12.
• Results Wang TD, Tan RS, Lee HY, Ihm SH, Rhee MY, Tomlinson B, Pal P, Yang F, Hirschhorn E, Prescott MF, Hinder M, Langenickel TH. Effects of Sacubitril/Valsartan (LCZ696) on Natriuresis, Diuresis, Blood Pressures, and NT-proBNP in Salt-Sensitive Hypertension. Hypertension. 2017 Jan;69(1):32-41. doi: 10.1161/HYPERTENSIONAHA.116.08484. Epub 2016 Nov 14.
• Results Ibrahim NE, Pina IL, Camacho A, Bapat D, Felker GM, Maisel AS, Butler J, Prescott MF, Abbas CA, Solomon SD, Januzzi JL Jr; Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entresto Therapy for Heart Failure (PROVE-HF) Study Investigators. Racial and Ethnic Differences in Biomarkers, Health Status, and Cardiac Remodeling in Patients With Heart Failure With Reduced Ejection Fraction Treated With Sacubitril/Valsartan. Circ Heart Fail. 2020 Nov;13(11):e007829. doi: 10.1161/CIRCHEARTFAILURE.120.007829. Epub 2020 Oct 3.
• Results Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K, Rocha R, Braunwald E; PIONEER-HF Investigators. Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure. N Engl J Med. 2019 Feb 7;380(6):539-548. doi: 10.1056/NEJMoa1812851. Epub 2018 Nov 11.
• Results Thomas M, Khariton Y, Fonarow GC, Arnold SV, Hill L, Nassif ME, Chan PS, Butler J, Thomas L, DeVore AD, Hernandez AF, Albert NM, Patterson JH, Williams FB, Spertus JA. Association between sacubitril/valsartan initiation and real-world health status trajectories over 18 months in heart failure with reduced ejection fraction. ESC Heart Fail. 2021 Aug;8(4):2670-2678. doi: 10.1002/ehf2.13298. Epub 2021 May 1.
• Results Green CP, Porter CB, Bresnahan DR, Spertus JA. Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure. J Am Coll Cardiol. 2000 Apr;35(5):1245-55. doi: 10.1016/s0735-1097(00)00531-3.
• Results McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30.
• Results 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. 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 Dec 3;400(10367):1938-1952. doi: 10.1016/S0140-6736(22)02076-1. Epub 2022 Nov 7.
• Results Raphael DM, Roos L, Myovela V, Mchomvu E, Namamba J, Kilindimo S, Gingo W, Hatz C, Paris DH, Weisser M, Kobza R, Rohacek M. Heart diseases and echocardiography in rural Tanzania: Occurrence, characteristics, and etiologies of underappreciated cardiac pathologies. PLoS One. 2018 Dec 26;13(12):e0208931. doi: 10.1371/journal.pone.0208931. eCollection 2018.
• Results Dokainish H, Teo K, Zhu J, Roy A, AlHabib KF, ElSayed A, Palileo-Villaneuva L, Lopez-Jaramillo P, Karaye K, Yusoff K, Orlandini A, Sliwa K, Mondo C, Lanas F, Prabhakaran D, Badr A, Elmaghawry M, Damasceno A, Tibazarwa K, Belley-Cote E, Balasubramanian K, Islam S, Yacoub MH, Huffman MD, Harkness K, Grinvalds A, McKelvie R, Bangdiwala SI, Yusuf S; INTER-CHF Investigators. Global mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study. Lancet Glob Health. 2017 Jul;5(7):e665-e672. doi: 10.1016/S2214-109X(17)30196-1. Epub 2017 May 3.
• Results Chillo P, Mlay J, Akanyirige PW, Majani N, Janabi M, Kaaya S, Hawkins C, Hirschhorn LR. Adapting and usability testing of the Kansas city cardiomyopathy questionnaire (KCCQ) in a heart failure clinic in Tanzania: the Swahili KCCQ. BMC Cardiovasc Disord. 2023 May 6;23(1):242. doi: 10.1186/s12872-023-03265-0.

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