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
AL
iskiren
O
bservation of Heart
F
ailure
T
reatment 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.
Direct renin inhibitor ameliorates insulin resistance by improving insulin signaling and oxidative stress in the skeletal muscle from post-infarct heart failure in mice
