The Effects of Vesnarinone on Morbidity and Mortality in Patient with Heart failure - Vesnarinone


Vesnarinone for mortality in heart failure.


Vesnarinone improves morbidity and mortality in heart failure patients treated with conventional therapy.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 477
NYHA Class: I (1%), II (18%), III (69%), IV (11%)
Mean Follow Up: 6 months
Mean Patient Age: 58
Female: 13
Mean Ejection Fraction: 20% (5-31%)

Patient Populations:

Heart failure symptoms despite conventional therapy
MUGA ejection fraction < 30%


Postpartum cardiomyopathy
Myocardial infarction or surgery in the prior 3 months
History of cardiac arrest
Implantable defibrillator
Creatinine > 2.4
Digoxin level > 1.8
History of drug induced hematologic disorder
Lupus erythematosus
Treatment with certain antiarrhythmic agents
Influenza vaccine in the prior three months
Absolute neutrophil count of < 2,000

Primary Endpoints:

Major cardiovascular morbidity and mortality (Morbidity was defined as hospital admission for inotropic treatment for worsening heart failure for at least 4 hours).

Secondary Endpoints:

Mortality - all cause

Drug/Procedures Used:

Vesnarinone 60 mg or 120 mg

Concomitant Medications:

ACE inhibitor (90%)
Digoxin (87%)
Antiarrhythmics (20%)
Diuretics (100%)

Principal Findings:

After 253 patients were enrolled, randomization to the 120 mg group was stopped because of significant increase in early mortality in this treatment group.

The group receiving 60 mg of Vesnarinone sustained significant reductions in morbidity and mortality (RR of 50%; p = 0.003).

All cause mortality reduced by 62% in Vesnarinone group.

Quality of life significantly improved in Vesnarinone group (p = 0.008).

2.5% of patients in Vesnarinone group had reversible neutropenia.


Six months of therapy with 60 mg of Vesnarinone per day resulted in lower morbidity and mortality and improved quality of life of life of patients with congestive heart failure. However, a higher dose of Vesnarinone (120 mg) increased mortality, suggesting that this drug has a narrow therapeutic range; the long-term effects of Vesnarinone are unknown. The results reported here were not supported in the subsequent VEST trial where 60 mg of Vesniranone was associated with a higher mortality rate. Results of inotropic therapy have been disappointing. The encouraging benefits observed with beta-adrenergic blockade cast increasing doubt on the long-term benefit of inotropic therapy.


1. N Engl J Med 1993;329:149-55. Final results

Clinical Topics: Heart Failure and Cardiomyopathies, Novel Agents, Statins, Acute Heart Failure

Keywords: Neutropenia, Digoxin, Quality of Life, Diuretics, Heart Failure, Quinolines, Adrenergic Antagonists

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