The Irbesartan in Heart Failure With Preserved Systolic Function (I-PRESERVE) Trial: Rationale and Design

Background: Although 40% to 50% of patients with chronic heart failure (HF) have relatively preserved systolic function (PSF), few trials have been conducted in this population and treatment guidelines do not include evidence-based recommendations. Methods and Results: The Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) is enrolling 4100 subjects with HF-PSF to evaluate whether 300 mg irbesartan is superior to placebo in reducing mortality and prespecified categories of cardiovascular hospitalizations. The principal inclusion criteria are age ≥60 years, heart failure symptoms, an ejection fraction ≥45%, and either hospitalization for heart failure within 6 months or corroborative evidence of heart failure or the substrate for diastolic heart failure. Additional secondary end points include cardiovascular mortality, cause-specific mortality and morbidity, change in New York Heart Association functional class, quality of life, and N-terminal pro-BNP measurements. Follow-up will continue until 1440 patients experience a primary end point. Substudies will evaluate changes in echocardiographic measurements and serum collagen markers. Conclusion: I-PRESERVE is the largest trial in this understudied area and will provide crucial information on the characteristics and course of the syndrome, as well as the efficacy of the angiotensin receptor blocker irbesartan

The Irbesartan in Heart Failure With Preserved Systolic Function (I-PRESERVE) Trial: Rationale and Design

Background: Although 40% to 50% of patients with chronic heart failure (HF) have relatively preserved systolic function (PSF), few trials have been conducted in this population and treatment guidelines do not include evidence-based recommendations. Methods and Results: The Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) is enrolling 4100 subjects with HF-PSF to evaluate whether 300 mg irbesartan is superior to placebo in reducing mortality and prespecified categories of cardiovascular hospitalizations. The principal inclusion criteria are age ≥60 years, heart failure symptoms, an ejection fraction ≥45%, and either hospitalization for heart failure within 6 months or corroborative evidence of heart failure or the substrate for diastolic heart failure. Additional secondary end points include cardiovascular mortality, cause-specific mortality and morbidity, change in New York Heart Association functional class, quality of life, and N-terminal pro-BNP measurements. Follow-up will continue until 1440 patients experience a primary end point. Substudies will evaluate changes in echocardiographic measurements and serum collagen markers. Conclusion: I-PRESERVE is the largest trial in this understudied area and will provide crucial information on the characteristics and course of the syndrome, as well as the efficacy of the angiotensin receptor blocker irbesartan

The baseline characteristics of patients enrolled in the irbesartan in heart failure with preserved systolic function trial are similar to those in the community but differ from charm-preserved

Background: Although 40-50% of heart failure (HF) patients (Pts) have normal or near-normal left ventricular EF, this group is rarely included in clinical trials, in part because of difficulty in recruiting older predominantly female Pts. Methods: I-PRESERVE is a randomized placebo-controlled trial of irbesartan (target dose 300 mg qd) in 4,128 Pts with symptomatic HF, age ≥60 years with EF ≥45% who were hospitalized for HF within 6 months or had specified echo, ECG, or X-ray findings consistent with diastolic dysfunction and/or HF. The primary endpoint is a composite of all-cause mortality or protocol-specified cardiovascular hospitalizations for non-fatal myocardial infarction, stroke, HF, unstable angina or dysrhythmia. Results: 4,128 Pts were entered in 293 sites from 24 countries. Their characteristics are shown in the table, along with data collated from epidemiology and cohort studies and, for comparison, those from CHARM-Preserved, the only large trial that has sought to recruit a similar group. Among I-Preserve Pts, 44% had been admitted for HF within 6 months, 40% had X-ray pulmonary congestion, 30% had ECG LVH, and 85% had either echo LVH or left atrial enlargement. Mean N-terminal BNP levels (Roche assay) were 843 ± 1594 pg/ml, consistent with the HF diagnosis. At baseline, 84% were taking diuretics, 62% beta-blockers, 44% calcium blockers, 27% ACE inhibitors (enrollment on background ACE inhibitors limited to 30% by protocol), and 20% spironolactone. Conclusions: I-Preserve succeeded in enrolling a population similar to that described in epidemiology studies, including a predominance of older Pts and women with underlying hypertension and relative infrequent CAD. Also noteworthy are important differences in many of these characteristics compared to the CHARM population. Results are anticipated in 2007