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Influence of diabetes on efficacy of aliskiren, losartan or both on left ventricular mass regression

Hypothesis/Introduction: We investigated whether diabetes modified the effectiveness of renin–angiotensin–aldosterone system (RAAS) inhibition on left ventricular hypertrophy (LVH) regression in hypertensive patients in the Aliskiren in Left Ventricular Hypertrophy (ALLAY) trial. Materials and methods: Participants (n=465) with LVH and a BMI > 25 kg/m2 were randomized to aliskiren 300mg, losartan 100mg or both daily for 36 weeks, and LVH regression was assessed by cardiac magnetic resonance imaging. Renin concentration, plasma renin activity and aldosterone were assessed in a subset of patients. Results: Patients with diabetes mellitus (DM) (n=111, 24%) were older (61±9 vs. 58±11 years, p=0.03), had higher BMI (32.2±4.2 vs. 30.7 ± 4 kg/m2, p=0.004), higher systolic blood pressure (148±14 vs. 145±14mmHg, p=0.03) and lower eGFR (79±16 vs. 84±16ml/min, p=0.03) at baseline. Combination therapy with aliskiren plus losartan was associated with greater LVH reduction than losartan alone in patients with DM (p=0.01), but not in patients without DM (p=0.91; unadjusted interaction p=0.06; adjusted p = 0.038). In a subset of 138 participants, plasma aldosterone was reduced to a greater extent in patients with DM (p-interaction = 0.004). Conclusions: Patients with DM and LVH may derive differential benefit with dual RAAS inhibition with a combination of aliskiren and losartan compared with losartan alone with respect to LVH reduction. Whether these findings will result in improved outcomes will be further explored in larger studies.