Sacubitril/valsartan Shows Benefit Over Enalapril In Heart Failure Caused By Chagas Disease

In patients pinch bosom nonaccomplishment (HF) caused by Chagas disease, sacubitril/valsartan was superior to enalapril for nan composite superior endpoint, predominantly driven by a important simplification successful N-terminal pro-B-type natriuretic peptide (NT-proBNP), according to late-breaking investigation presented successful a Hot Line convention coming astatine ESC Congress 2025.

Chagas disease, caused by Trypanosoma cruzi infection, remains a superior wellness problem affecting much than 7 cardinal people, chiefly from Latin America. T. cruzi parasites are chiefly transmitted by interaction pinch faeces/urine of infected triatomine bugs. T. cruzi can besides beryllium transmitted by depletion of contaminated food/beverages, during gestation aliases birth, done blood/blood products, organ transplantation and laboratory accidents. Chagas illness is spreading astir nan world, predominantly owed to migration of infected patients to different regions, including North America, Europe, Asia and Australia. Chagas cardiomyopathy is considered nan astir communal and superior manifestation of chronic Chagas disease, occurring successful 30-40% of infected group during semipermanent follow-up.

HF caused by Chagas illness has unsocial objective features pinch worse prognosis than different causes of HF contempt nan truth that patients are often younger and person less comorbidities. There person been nary prospective randomized tests testing nan effects of modular treatments successful patients pinch Chagas illness and HF. In nan wide HF population, nan angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan improved HF outcomes vs. nan angiotensin-converting enzyme inhibitor, enalapril, and we compared these 2 agents successful nan largest proceedings successful patients pinch Chagas illness and HF conducted to date."

Professor Renato Lopes from Duke University Medical Center, Durham, USA, Principal Investigator of nan PARACHUTE-HF trial

PARACHUTE-HF was an academic-led, open-label, blinded-endpoint adjudication, randomized proceedings conducted astatine much than 80 sites successful Brazil, Argentina, Mexico and Colombia. Eligibility criteria included a test of Chagas illness confirmed by astatine slightest 2 different serological tests affirmative for Trypanosoma cruzi infection, near ventricular ejection fraction (LVEF) ≤40%, New York Heart Association functional people II to IV symptoms and NT-proBNP ≥600 pg/ml aliases ≥400 pg/ml and hospitalization for HF wrong nan past 12 months. Participants were randomized 1:1 to either sacubitril/valsartan (50 aliases 100 mg doubly regular titrated to a target of 200 mg doubly daily) aliases enalapril (2.5 aliases 5 mg doubly regular titrated to a target of 10 mg doubly daily). The superior endpoint was a hierarchical composite result consisting of cardiovascular death, first hospitalization for HF and nan comparative alteration from baseline to week 12 successful NT-proBNP, analysed utilizing a triumph ratio approach.

In total, 922 patients were randomized. The mean property was 64 years, 42.0% were women, mean LVEF was 29.8% and 44.4% had had anterior hospitalization for HF.

Following pairwise comparisons, sacubitril/valsartan was associated pinch a 52% higher likelihood of a amended superior result compared pinch enalapril (stratified unmatched triumph ratio 1.52; 95% assurance interval [CI] 1.28 to 1.82; p<0.001). Over a median of 25 months' follow-up, rates were akin for sacubitril/valsartan vs. enalapril for cardiovascular decease (hazard ratio [HR] 0.95; 95% CI 0.73 to 1.23) and first HF hospitalization (HR 0.92; 95% CI 0.70 to 1.20). The important quality successful nan superior result was predominantly driven by nan percent alteration successful NT-proBNP from baseline to 12 weeks: logarithmic median alteration from baseline was −30.6% successful those assigned to sacubitril-valsartan and −5.5% successful those assigned to enalapril (ratio of adjusted geometric mean alteration 0.68; 95% CI 0.62 to 0.75).

The information profiles of nan 2 agents were similar, pinch discontinuations owed to adverse events occurring successful 6.1% of patients pinch sacubitril/valsartan and 9.8% pinch enalapril.

Concluding, Professor Lopes said: "In patients pinch HF caused by Chagas disease, sacubitril/valsartan was superior to enalapril pinch respect to nan superior outcome, predominantly driven by nan 32% simplification successful NT-proBNP levels astatine week 12. Our study provides nan first randomized proceedings grounds to support a pharmacological curen specifically successful this high-risk population. PARACHUTE-HF shows that much-needed studies to amended characterise chronic Chagas cardiomyopathy and to specify nan benefit/risk of caller therapies successful this information are possible. In statement pinch nan world wellness spotlight of ESC Congress, nan PARACHUTE-HF proceedings provides a successful exemplary for world collaborations - successful this section among cardiologists and infectious illness physicians − pinch nan shared extremity of evaluating nan effect of caller therapies connected cardiovascular outcomes successful patients pinch neglected diseases."