The Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) study evaluated the effects of irbesartan, an angiotensin-receptor blocker, on mortality and cardiovascular morbidity in patients with heart failure and a preserved left ventricular ejection fraction (LVEF). The study enrolled 4128 patients aged 60 years or older with New York Heart Association (NYHA) class II, III, or IV heart failure and an LVEF of at least 45%. Patients were randomly assigned to receive either 300 mg of irbesartan or a placebo daily. The primary composite outcome was death from any cause or hospitalization for a cardiovascular cause, including heart failure, myocardial infarction, stroke, or arrhythmia. Secondary outcomes included death from heart failure, hospitalization for heart failure, death from any cause, and quality of life. Over a mean follow-up of 49.5 months, 742 patients in the irbesartan group and 763 in the placebo group experienced the primary outcome. The hazard ratio for the primary outcome was 0.95 (95% CI, 0.86 to 1.05; P=0.35), indicating no significant difference between the groups. There were no significant differences in other prespecified outcomes, including overall mortality and hospitalization rates for cardiovascular causes. The study found that irbesartan did not improve outcomes in patients with heart failure and a preserved LVEF. These findings contrast with the benefits seen with renin-angiotensin-aldosterone system inhibitors in patients with heart failure and a low LVEF. However, the results are consistent with two other studies involving patients with preserved LVEF, the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM)–Preserved trial and the Perindopril in Elderly People with Chronic Heart Failure (PEP-CHF) trial. The lack of benefit may be due to factors such as the difficulty in diagnosing heart failure with preserved LVEF, the high rate of study drug discontinuation, and the use of multiple renin-angiotensin system inhibitors. The study also found that important targets for renin-angiotensin blockade may have been absent in this population. Despite these findings, aldosterone antagonists may have more success in treating heart failure with preserved LVEF, as aldosterone plays a major role in myocardial collagen formation. The Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial is currently evaluating this possibility.The Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) study evaluated the effects of irbesartan, an angiotensin-receptor blocker, on mortality and cardiovascular morbidity in patients with heart failure and a preserved left ventricular ejection fraction (LVEF). The study enrolled 4128 patients aged 60 years or older with New York Heart Association (NYHA) class II, III, or IV heart failure and an LVEF of at least 45%. Patients were randomly assigned to receive either 300 mg of irbesartan or a placebo daily. The primary composite outcome was death from any cause or hospitalization for a cardiovascular cause, including heart failure, myocardial infarction, stroke, or arrhythmia. Secondary outcomes included death from heart failure, hospitalization for heart failure, death from any cause, and quality of life. Over a mean follow-up of 49.5 months, 742 patients in the irbesartan group and 763 in the placebo group experienced the primary outcome. The hazard ratio for the primary outcome was 0.95 (95% CI, 0.86 to 1.05; P=0.35), indicating no significant difference between the groups. There were no significant differences in other prespecified outcomes, including overall mortality and hospitalization rates for cardiovascular causes. The study found that irbesartan did not improve outcomes in patients with heart failure and a preserved LVEF. These findings contrast with the benefits seen with renin-angiotensin-aldosterone system inhibitors in patients with heart failure and a low LVEF. However, the results are consistent with two other studies involving patients with preserved LVEF, the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM)–Preserved trial and the Perindopril in Elderly People with Chronic Heart Failure (PEP-CHF) trial. The lack of benefit may be due to factors such as the difficulty in diagnosing heart failure with preserved LVEF, the high rate of study drug discontinuation, and the use of multiple renin-angiotensin system inhibitors. The study also found that important targets for renin-angiotensin blockade may have been absent in this population. Despite these findings, aldosterone antagonists may have more success in treating heart failure with preserved LVEF, as aldosterone plays a major role in myocardial collagen formation. The Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial is currently evaluating this possibility.