Carvedilol as a single-drug therapy for Heart Failure with recovered ejection fraction: an open label randomized clinical trial

INTERVENTION: 60 ambulatorial patients will be randomized 1:1 by independent random sample to either keep standard heart failure treatment (control group) or have renin‐angiotensin‐system inhibitors and neprilisin inhibitors withdrown keeping carvedilol (intervention group). The intervention group will have the referred medications gradually reduced until suspension. In the first evaluation, spironolactone will be suspended if daily dose is equal or less than 50mg, and furosemide will be suspended if daily dose equal or less than 40mg; if daily dose is above those values, medications will have daily dose reduced by half, and, after two teeks, they will be suspended. After this, angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers or neprilisin inhibitor will have daily dose reduced by half every two weeks until daily dose is equal or less than 25% of target dose. Patients will then be followed for 24 weeks. Patients randomized to placebo group will not have their medications altered, and will be also followed for 24 weeks. All patients will be clinically evaluated every six weeks, and NT‐proBNP will be dosed in the begging, after 12 weeks and after 24 weeks. Echocardiogram, ergospirometry, Minnesota Living with Heart Failure Questionnaire, REMADHE questionnaire and 6‐minute walk test will be performed in the beginning and after 24 weeks. D02.033.100.624.151 CONDITION: I50 Left‐side heart failure PRIMARY OUTCOME: Evaluate relapse of ventricular dysfunction in 6 months. We will consider a positive outcome if the patient fulfill one of the following criteria: reduction in left ventricular ejection fraction by more than 10% to less than 50% using transthoracic echocardiogram; an increase in left end diastolic left ventricular diameter by more than 10% and to higher the normal range using transthoracic echocardiogram; a 100% increase in N‐terminal pro‐brain natriuretic peptide to more than 400pg/mL; or clinical evidence of heart failure ; SECONDARY OUTCOME: We will evaluate mortality in 24 weeks Evaluation of distance in meters achieved in 6‐minute walk test We will evaluate medication adherence by the questionnaire used in Repetitive Education and Monitoring for ADherence for Heart Failure study We will evaluate if hospitalization due to decompensated heart failure will happen We will evaluate quality of life using the validated by Minnesota Living with Heart Failure Questionnaire Peak oxygen uptake value in ergospirometry in milliliters per kilogram per minute We will evaluate echocardiographic parameters using transthoracic echocardiogram: left atrial volume and size, left ventricular systolic and diastolic diameters, diastolic left ventricular function, right ventricular function, presence and graduation of valvar insufficiencies, systolic pulmonary artery pressure, contractility score of left ventricular function in a 17 segments model We will evaluate heart rate in beats per minute and blood pressure in millimeters of mercury We will evaluate occurrence of sustained supraventricular and ventricular arrhythmias using clinical evaluation INCLUSION CRITERIA: Patients with previous diagnosis of reduced ejection fraction heart failure and documented ejection fraction equal or under 40% and actual ejection fraction equal or more than 50% and 10% greater than previous; Age equal or greater than 18 years old; absence of symptoms related to heart failure; Currently using carvedilol and angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers or neprilisin inhibitor with or without spironolactone; NT‐proBNP under 250pg/mL; heart rate between 50 and 60 or maximum tolerated dose of carvedilol after runin fase or at least 50mg/day of carvedilol.