Abstract 2491: Neurohumoral Effects Of A New Oral Direct Renin Inhibitor In Stable Heart Failure: The Aliskiren Observation Of Heart Failure Treatment Study (ALOFT).
Background: Treatments that inhibit the renin-angiotensin-aldosterone system (RAAS) are of established benefit in heart failure (HF). These include ACE-inhibitor, angiotensin receptor blockers (ARB) and aldosterone antagonists (AA). In addition, beta blockers (BB) are also effective inhibitors of renin secretion. In this first placebo-controlled study, we have investigated whether the new orally-active direct renin inhibitor, aliskiren, has additional neurohumoral actions when added to these proven therapies.
Methods: Inclusion criteria for the ALiskiren Observation of Heart Failure Treatment study (ALOFT) were: age 18 years or older, stable heart failure with NYHA functional class II–IV, prior or current hypertension, plasma B-type natriuretic peptide (BNP) concentration >100 pg/mL and treatment with an ACE-I or ARB and BB, unless contraindicated or not tolerated. Patients were randomized to 3 months double-blind treatment with placebo or aliskiren (150 mg qd), added to standard therapy.
Results: Overall, 302 patients (78% male, mean age 68 years, mean LVEF 31%) were randomized. Baseline treatment: 84% ACE-I, 15% ARB, 94% BB and 33% AA. Change in neurohormones versus baseline are shown in the table⇓ (expressed as % change using geometric means in an analysis of covariance model). Aliskiren significantly suppressed plasma renin activity (PRA), BNP and urinary aldosterone excretion overall and to a similar extent in patients treated and not treated with an AA.
Conclusions: Aliskiren suppresses PRA in patients treated with a beta blocker and has additional and potentially beneficial neurohumoral effects in patients already comprehensively treated with neuroendocrine antagonists.