ADEPT: Addition of the AT(1) receptor antagonist eprosartan to ACE inhibitor therapy in chronic heart failure trial: Hemodynamic and neurohormonal effects

Background Persistent activation of the renin-angiotensin-aldosterone-syste m (RAAS) is known to occur in patients with chronic heart failure (CHF) des pite treatment with angiotensin-converting enzyme inhibitor (ACE) therapy. When added to ACE inhibitors, angiotensin II type 1 (AT(1)) antagonists may allow more complete blockade of the RAAS and preserve the beneficial effec ts of bradykinin accumulation not seen with AT(1) receptor blockade alone. Methods Thirty-six patients with stable New York Heart Association class II -IV CHF receiving ACE inhibitor therapy were randomly assigned in a double- blind manner to receive either eprosartan, a specific competitive AT(1) rec eptor antagonist (400 to 800 mg daily, n = 18) or placebo (n = 18) for 8 we eks. The primary outcome measure was left ventricular ejection fraction (LV EF) as measured by radionuclide ventriculography, and secondary measures we re central hemodynamics assessed by Swan-Ganz catheterization and neurohorm onal effects. Results There was no change in LVEF with eprosartan therapy (mean relative LVEF percentage change [SEM] + 10.5% [9.3] vs + 10.1% [5.0], respectively; difference, 0.4; 95% confidence interval [CI], -20.8 to 21.7; P = .97). Epr osartan was associated with a significant reduction in diastolic blood pres sure and a trend toward a reduction in systolic blood pressure compared wit h placebo (-7.3 mm Hg [95% CI, -14.2 to -0.4] diastolic; -8.9 mm Hg [95% CI , -18.6 to 0.8] systolic). No significant change in heart rate or central h emodynamics occurred during treatment with eprosartan compared with Placebo . A trend toward an increase in plasma renin activity was noted with eprosa rtan therapy. Eprosartan was well tolerated, with an adverse event profile similar to placebo, whereas kidney function remained unchanged. Conclusions When added to an ACE inhibitor, eprosartan reduced arterial pre ssure without increasing heart rate. There was no change in LVEF after 2 mo nths of therapy with eprosartan.