Losartan in Decompensated Heart Failure

Study Overview
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Brief Summary
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The dual blockade of the renin-angiotensin-aldosterone system with an angiotensin-converting enzyme inhibitor and an angiotensin-receptor blocker used together in heart failure patients has been demonstrated to be beneficial. However, the dual inhibition has not been studied during heart failure decompensation or even when low cardiac output is present. The objective of this study was to assess the effects of add-on therapy with angiotensin receptor blocker on plasma B-type natriuretic peptide levels and hemodynamic measurements in heart failure patients with low cardiac output during hospitalization for decompensation. This was a randomized, double-blind, placebo-controlled clinical trial.

Detailed Description
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The inclusion criteria were hospitalization for decompensated heart failure defined by worsening of symptoms until fatigue or dyspnea at rest, low cardiac output defined by the clinical-hemodynamic profile, dobutamine dependence, and ejection fraction < 0.45, spontaneous breathing and receiving angiotensin-converting enzyme inhibitors. The patients could have jugular ingurgitation, lower limbs edema, ascites and rales. Dobutamine dependence was defined by infusion for more than 15 days or an unsuccessful attempt of withdrawal. The exclusion criteria were serum creatinine > 3.0 mg/dL, serum potassium > 6.0 mEq/L, systolic blood pressure < 70 mm Hg, aortic stenosis, and acute coronary syndrome in the previous 2 months. The patients were randomly assigned by permuted block of 4, stratified by sex, to losartan or placebo. The endpoints were change in B-type natriuretic peptide levels, cardiac index, pulmonary wedge capillary pressure, systemic vascular resistance, and successful withdrawal of dobutamine.

Official Title
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Short-term add-on Therapy With Angiotensin Receptor Blocker for End-stage Inotrope-dependent Heart Failure Patients: B-type Natriuretic Peptide Reduction in a Randomized Clinical Trial

Conditions
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Congestive Heart Failure, Low Cardiac Output

Intervention / Treatment
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* Drug: Losartan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: hospitalization for decompensated heart failure dobutamine dependence ejection fraction < 0.45 taking angiotensin-converting enzyme inhibitor Exclusion Criteria: serum creatinine > 3.0 mg/dL serum potassium > 6.0 mEq/L systolic blood pressure < 70 mm Hg aortic stenosis acute coronary syndrome in the previous 2 months
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Losartan<br>Losartan 50 mg bid orally | Drug: Losartan<br> <br> |
| Placebo Comparator: Placebo<br>Placebo 1 pill bid orally | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| B-type natriuretic peptide | Serum B-type natriuretic peptide | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful withdrawal from dobutamine | Successful withdrawal from dobutamine with clinical stability | 7 days | 
| Worsening renal function | Increase > 0.3 mg/dL in serum creatinine | 7 days | 
| Hyperkalemia | Serum potassium > 5.5 mEq/L | 7 days | 
| Hypotension | Systolic blood pressure < 80 mmHg | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renin-aldosterone system, Hemodynamic, Low cardiac output, Vasodilation, Natriuretic peptide