A randomized trial of carvedilol after renin-angiotensin system inhibition in chronic Chagas cardiomyopathy.
OBJECTIVE
The objective of this study was to determine the safety and efficacy of renin-angiotensin system (RAS) inhibitors and beta-blockers in chronic Chagas cardiomyopathy.


BACKGROUND
Chronic Chagas cardiomyopathy causes substantial morbidity and mortality in Latin America. Whether RAS inhibitors and beta-blockers are safe and beneficial has been challenged because of the lack of formal trials.


METHODS
We conducted a double-blind, placebo-controlled, and randomized trial in 42 patients with Trypanosoma cruzi infection and cardiomyopathy. All patients received enalapril (up-titrated to 20 mg BID) and spironolactone (25 mg QD). Subsequently, the patients were randomly assigned to receive placebo (n = 20) or carvedilol up-titrated to 25 mg BID (n = 19). The primary end points were change in left ventricular ejection fraction (LVEF) after RAS inhibition and that after the addition of carvedilol. The secondary end points were changes in other echocardiographic parameters, Framingham score, quality of life (36-item Short-Form Health Survey), New York Heart Association class, radiographic indices, brain natriuretic peptide levels, and chemokines as well as safety end points.


RESULTS
Optimization of RAS inhibition was safe, hemodynamically well tolerated, and associated with improvements in Framingham score (P = .001) and quality of life as well as reductions in the cardiothoracic index (P = .002), brain natriuretic peptide level (P = .032), and RANTES (regulated on activation, normal T expressed and secreted) level (P = .001). Left ventricular ejection fraction increased by 2.3% (P = .25); in patients with an LVEF < or = 45% at baseline, it increased by 2.8% (P = .017). Treatment with carvedilol was associated with a trend toward an increase in LVEF (absolute difference between groups, 2.3%; P = .094). The addition of carvedilol was safe, hemodynamically well tolerated, and not associated with symptomatic bradycardia.


CONCLUSIONS
In patients with chronic Chagas cardiomyopathy, optimization of treatment with enalapril and spironolactone and subsequent addition of carvedilol were safe and associated with benefits in cardiac function and clinical status. Larger trials are needed to show effects on mortality and/or hospitalization.
Botoni
Fernando A
FA
Postgraduate Course of Tropical Medicine, University Hospital, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. fbotoni@medicina.ufmg.br
Poole-Wilson
Philip A
PA
Ribeiro
Antonio L P
AL
Okonko
Darlington O
DO
Oliveira
Bráulio M R
BM
Pinto
Airandes S
AS
Teixeira
Mauro M
MM
Teixeira
Antonio L
AL
Reis
Adelina M
AM
Dantas
Jackellyne B P
JB
Ferreira
Cid S
CS
Tavares
Wilson C
WC
Rocha
Manoel Otávio C
MO
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D002598:Chagas Cardiomyopathy; D002908:Chronic Disease; D004311:Double-Blind Method; D004656:Enalapril / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D011412:Propanolamines / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013148:Spironolactone / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002227:Carbazoles; D000451:Mineralocorticoid Receptor Antagonists; D011412:Propanolamines; D000077261:Carvedilol; D013148:Spironolactone; D004656:Enalapril