Dual Renin–angiotensin System Blockade with Aliskiren in Patients with Heart Failure, with or without Diabetes Mellitus: Insights from ALOFT

Abstract

Aims: Because of recent concerns about the safety of dual renin–angiotensin–aldosterone system (RAAS) blockade with a renin inhibitor in patients with hypertension and diabetes mellitus (DM), we have conducted a retrospective analysis of the effect of this treatment in patients with and without diabetes in the Aliskiren Observation of Heart Failure Treatment study (ALOFT). Methods and results: In ALOFT, patients with stable New York Heart Association class II–IV heart failure (HF) and plasma B-type natriuretic peptide (BNP) concentration >100 pg/mL were randomised to Aliskiren 150 mg/d or placebo, added to optimal HF therapy, for 12 weeks. In addition to greater central adiposity and dysglycaemia, HF patients with DM had more oedema, elevated blood urea and urinary albumin/creatinine ratio, and increased plasma renin activity (PRA) and concentration. They also had evidence of greater left ventricular hypertrophy, increased collagen turnover, left atrial enlargement and mitral regurgitation. Aliskiren had similar effects in patients with and without DM, reducing BNP, NT proBNP and PRA equally in both groups. The incidence of adverse effects related to hypotension, hyperkalaemia and renal dysfunction was low in each patient group and was not increased, significantly, with Aliskiren. Conclusions: HF patients with DM have elevated PRA compared to those without DM. Aliskiren causes equivalent neurohumoral suppression in HF patients with and without DM.