CLINICAL STUDIES
Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan in heart failure
Edward P. Havranek, MD, FACC*,
Ignatius Thomas, MD ,
William B. Smith, MD ,
George A. Ponce, MD ,
Martin Bilsker, MD, FACC||,
Mark A. Munger, PharmD¶,
Robert A. Wolf, MD, FACC# for the Irbesartan Heart Failure Group
* Denver Health Medical Center, University of Colorado Health Sciences Center, Denver, Colorado, USA
Slidell Memorial Hospital, Slidell, Louisiana, USA
Louisiana Cardiovascular Research Center, New Orleans, Louisiana, USA
Adult Cardiovascular Disease, Hemet, California, USA
|| University of Miami School of Medicine, Miami, Florida, USA
¶ University of Utah Heart Failure Treatment Program, Salt Lake City, Utah, USA
# Bristol-Myers Squibb, Princeton, New Jersey, USA
Manuscript received February 19, 1998;
revised manuscript received October 9, 1998,
accepted December 22, 1998.
Reprint requests and correspondence: Dr. Edward P. Havranek, Denver Health Medical Center #0960, 777 Bannock Street, Denver, Colorado 80204-4507 ehavrane{at}dhha.org
OBJECTIVES
The primary purpose of this study was to determine the acute and long-term hemodynamic and clinical effects of irbesartan in patients with heart failure.
BACKGROUND
Inhibition of angiotensin II production by angiotensin-converting enzyme (ACE) inhibitors reduces morbidity and mortality in patients with heart failure. Irbesartan is an orally active antagonist of the angiotensin II AT1 receptor subtype with potential efficacy in heart failure.
METHODS
Two hundred eighteen patients with symptomatic heart failure (New York Heart Association [NYHA] class IIIV) and left ventricular ejection fraction 40% participated in the study. Serial hemodynamic measurements were made over 24 h following randomization to irbesartan 12.5 mg, 37.5 mg, 75 mg, 150 mg or placebo. After the first dose of study medication, patients receiving placebo were reallocated to one of the four irbesartan doses, treatment was continued for 12 weeks and hemodynamic measurements were repeated.
RESULTS
Irbesartan induced significant dose-related decreases in pulmonary capillary wedge pressure (average change 5.9 ± 0.9 mm Hg and 5.3 ± 0.9 mm Hg for irbesartan 75 mg and 150 mg, respectively) after 12 weeks of therapy without causing reflex tachycardia and without increasing plasma norepinephrine. The neurohormonal effects of irbesartan were highly variable and none of the changes was statistically significant. There was a significant dose-related decrease in the percentage of patients discontinuing study medication because of worsening heart failure. Irbesartan was well tolerated without evidence of dose-related cough or azotemia.
CONCLUSIONS
Irbesartan, at once-daily doses of 75 mg and 150 mg, induced sustained hemodynamic improvement and prevented worsening heart failure.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | BUN | = blood urea nitrogen | | CI | = cardiac index | | LVEF | = left ventricular ejection fraction | | MPAP | = mean pulmonary arterial pressure | | MRAP | = mean right atrial pressure | | MSAP | = mean systemic arterial pressure | | NYHA | = New York Heart Association | | PCWP | = pulmonary capillary wedge pressure |
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