The I-PRESERVE study is supported by a grant from Bristol-Myers Squibb Co. and Sanofi-Synthelabo Inc.
I-PRESERVE is the first and largest clinical trial to focus exclusively on patients with heart failure and preserved systolic function (HF-PSF), an increasingly common but often underdiagnosed condition in which no morbidity-mortality trial has ever been conducted. It is estimated that there are currently 15 to 20 million patients worldwide with HF-PSF.
"At present, there is a paucity of clinical data to guide management of patients with heart failure with preserved left ventricular systolic function, a condition which occurs in up to 50 percent of heart failure patients," said Carson, chief of the Medical Intensive Care Unit of the Department of Veterans’ Affairs’ Medical Center and associate professor of medicine of Georgetown University of Hospital, Washington, D.C.
"Now as a result of several epidemiological studies in the United States and Europe, heart failure with preserved systolic function is emerging as the most common form of heart failure, especially in older patients and women. The I-PRESERVE study will lead us in a new direction in the understanding of cardiovascular disease as it will focus on exploring the impact of treatment in an understudied population," he added.
Only in the last few years has it been observed that up to 50 percent of patients with heart failure have normal or near-normal left ventricular ejection fractions, the usual index of cardiac contractile function.
However, because the left ventricle becomes excessively stiff, it is unable to fill normally, causing what is termed as diastolic dysfunction/heart failure or heart failure with preserved systolic function. Although this is probably the most frequent form of heart failure in the elderly and in women, and associated with higher rates of mortality and hospitalization, no clinical trial has yet been completed in this population and treatment remains entirely empirical.
Nonetheless, there are a number of reasons which suggest that treatment with an angiotensin II receptor antagonist (AIIRA) such as irbesartan, which effectively treats hypertension, reduces left ventricular hypertrophy, and reduces the renal complications of type 2 diabetes, all of which often underlie diastolic heart failure, could be effective.
"Early evidence has suggested that angiotensin II receptor blockers may be effective in the treatment of heart failure patients," said Carson. "I-PRESERVE will enable us to determine if irbesartan can prolong survival and reduce cardiovascular morbidity in patients who have preserved systolic function (normal or almost normal) and clinical symptoms of heart failure that could be due to altered diastolic dysfunction."
The primary objective of I-PRESERVE is to determine whether irbesartan is effective in saving lives and decreasing cardiovascular hospitalization in patients with heart failure and preserved systolic function.
I-PRESERVE is a multi-center, randomized, double-blind, placebo-controlled trial with planned enrollment of 3,600 patients in up to 400 clinical centers in Western and Eastern Europe, the United States, Canada, Latin America, Australia and South Africa.
All patients enrolled in the study will be over 60 years old, have symptomatic heart failure and a left ventricular ejection fraction (LVEF) greater than 45 percent. All patients in the study will continue to receive background therapy appropriate to their cardiovascular condition.