Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes

Study Questions:

What are the efficacy and safety of aliskiren, a direct renin inhibitor, among patients with type 2 diabetes mellitus already taking an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin-receptor blocker (ARB)?


ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints) was a randomized, double-blind, placebo-controlled, international, and multicenter trial. The primary endpoint was a composite of cardiovascular and renal outcomes.


After a median follow-up of 32.9 months, the primary cardiorenal composite outcome had occurred in 783 participants in the aliskiren group (18.3%), as compared to 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98-1.20; p = 0.12). This overall lack of benefit was observed across all predefined subgroups. The trial was terminated prematurely based on the independent Data and Safety Monitoring Committee’s assessment that the excess risk of adverse events in the aliskiren group could not be countered by a reduction in cardiovascular and renal events. Compared to placebo, the addition of aliskiren was associated with an increased number of adverse events. In particular, the proportion of patients with hyperkalemia (serum potassium level ≥6 mmol/L) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%).


The direct renin inhibitor, aliskiren, when added to standard renin-angiotension blockade in type 2 diabetic patients and compared to placebo, did not improve cardiovascular and renal outcomes, and was associated with an increased number of adverse events.


Even though two trials in which aliskiren is being given to heart failure patients already taking ACE inhibitor or ARB are continuing, the present study from the ALTITUDE investigators has documented more harm among those receiving aliskiren, compared to placebo, without any meaningful clinical benefit.

Keywords: Fumarates, Diabetes Mellitus, Type 2, Hyperkalemia

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