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

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 238 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®.

Background Non-communicable diseases (NCDs) cause more than 40 million deaths globally each year, and more than three quarters of them occur in low- and middle-income countries. The majority of deaths are caused by cardiovascular diseases, such as heart failure and stroke. Mortality from heart failure has been reported to be highest in Africa, with a one-year mortality rate of 34% compared to 16.5% in other low- and middle-income countries. Arterial hypertension is the most common underlying risk factor for heart failure in sub-Saharan Africa, also in rural areas. Patients mostly present in advanced stages of heart failure, and are not under regular treatment. International guidelines recommend diuretics, angiotensin- converting enzyme (ACE) inhibitors or angiotensin-neprilysin inhibitors (ARNI), angiotensin 2 receptor blockers (ARB), if ACE-inhibitors are not tolerated, beta-blockers, mineralocorticoid receptor antagonists, and sodium glucose co- transporter 2 (SGLT-2) inhibitors for treatment of chronic heart failure with reduced ejection fraction. An intensive treatment strategy with rapid up-titration of guideline-directed chronic heart failure therapy after acute heart failure reduces symptoms, improves quality of life, reduces the risk for all cause death, and is well tolerated. The PARADIGM trial showed that, if enalapril 10mg twice daily for at least 2 weeks was switched to sacubitril/valsartan in symptomatic patients with a left ventricular ejection fraction (LVEF) of ≤40% who had been under a stable heart failure therapy for at least 4 weeks, the combined endpoint of death and hospitalization for heart failure was significantly reduced from 26.5% to 21.8% compared to if the ACE inhibitor was continued. In the CHAMP-HF, a multicenter observational study of American outpatients with heart failure with reduced ejection fraction (HFrEF), 35.8% patients initiated on ARNI had a large (10 to \<20 points) or very large (20 points and more out of 100) improvement in their health status expressed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score measured by the KCCQ-12 short version over a median (IQR) of 10.7 (6.7 -11.7) months of follow up, vs 27.5% of patients not initiated on ARNI. Among patients with HFrEF who were hospitalized for acute decompensated heart failure, the initiation of sacubitril/valsartan therapy led to a greater reduction in the N-terminal pro brain natriuretic peptide (NT-proBNP) blood concentration than enalapril therapy. One study could not detect any racial and ethnic differences in reduction of NT-proBNP, improvement in health status, and reverse remodeling in patients with systolic heart failure treated with sacubitril/valsartan. In patients with salt-sensitive hypertension, sacubitril/valsartan was superior to valsartan in office- and ambulatory blood pressure control, and was associated with an increased natriuresis and diuresis. Moreover, sacubitril-valsartan had a positive effect on glycemic cont Покажи пълното описание...

Inclusion criteria * Symptomatic heart failure NYHA class II-IV and * Left ventricular ejection fraction (LVEF) ≤40% and * Treatment with an ACE Inhibitor or an ARB, beta-blocker, and spironolactone in recommended dosages for at least 3 months, and * Adherence to this therapy of at least 80%. Exclusion criteria * Pregnancy * Systolic blood pressure of less than 95 mmHg, * eGFR below 30 ml per minute per 1.73 m2 of body-surface area * Serum potassium level of more than 5.4 mmol per liter * History of angioedema * Unacceptable side effects prior during receipt of ACE inhibitors or ARBs * Inability to sign an informed consent form.