Effect of Furosemide Withdraw in Stable Chronic Heart Failure Outpatients With Left Ventricular Dysfunction - the Brazilian Research Network on Heart Failure

Diuretics play a central role in HF treatment, particularly during episodes of acute decompensation. Furosemide is the prototype of loop diuretics, acting through the inhibition of the Na+K+2Cl- pump at the thick ascending limb of the Henle loop. According to international registries, almost all patients receive a loop diuretic during a hospital stay for acute decompensated HF and the majority are discharged taking a "maintenance dose". Despite the undeniable beneficial hemodynamic effects of improvement of peripheral and central congestion, the net clinical effect of the chronic use of diuretics on HF prognosis is controversial.

Observational studies suggest that use of high doses of diuretics might be related to unfavorable clinical consequences. Undesirable side effects of loop diuretics are not trivial and involve activation of the renin-angiotensin-aldosterone system, elevation of norepinephrine levels, increases in heart rate, detrimental effects on renal function and several electrolyte disturbances.

Few prospective clinical studies, however, directly evaluated the clinical risks and benefits of diuretics. Most of these studies were under-powered, performed more than 2 decades ago, before modern HF therapy with current drugs and devices was completely implemented.

Current clinical guidelines are unanimous to recommend use of diuretics in HF patients with clinical signs and symptoms of congestion, but reinforce the lack of solid clinical scientific evidence for its use, and the potential risks that might be involved. The European Society of Cardiology proposes the administration of the lowest dose necessary to achieve euvolemia, avoiding the unnecessary delay in the use of drugs that modify the natural history of the disease.

Based on these uncertainties about diuretic use in HF, the ReBIC-1 trial was designed to evaluate the potential clinical risks and benefits of withdrawing furosemide use in stable, apparently euvolemic, chronic HF outpatients in a multicentric double-blinded randomized clinical trial.