Clinical Question

In patients with diabetes mellitus and renal or heart disease, does the direct renin inhibitor aliskiren (Tekturna) improve outcomes?

Bottom Line

Aliskiren increases the likelihood of adverse cardiovascular outcomes in patients with diabetes and kidney or heart disease, and cannot be recommended. (Level of Evidence = 1b)

Synopsis

In this study, more than 8,500 patients older than 35 years with type 2 diabetes who also had evidence of microalbuminuria, macroalbuminuria, or coronary artery disease were randomized to receive aliskiren or placebo. The drug was initially given in a daily dosage of 150 mg and was increased to 300 mg if tolerated. The mean age of participants was 64 years, 32% were women, 13% were smokers, and the average A1C level was 7.8. Groups were balanced at the start of the study, and follow-up was good (with a mean follow-up of 2.8 years and less than 3% lost). The study was stopped after the second interim analysis because of an increase in the likelihood of the primary composite outcome among patients in the aliskiren group. This composite included cardiovascular death, cardiac arrest, myocardial infarction, stroke, unplanned hospitalization for heart failure, end-stage renal disease or death due to renal failure, or doubling of serum creatinine levels. This occurred in 18.3% of the aliskiren group and 17.1% of the placebo group (hazard ratio = 1.08; 95% confidence interval, 0.98 to 1.2). The only individual end point with a statistically significant difference between groups was cardiac arrest (0.4% for aliskiren vs. 0.2% for placebo; P = .04; number needed to harm = 500). However, the trend for all other outcomes but two (doubling of serum creatinine and unplanned hospitalization for heart failure) favored the placebo group. Hyperkalemia and hypotension were among the most common reasons that the drug was discontinued, and were significantly more common in patients taking aliskiren.

Reference

ParvingHHBrennerBMMcMurrayJJet alALTITUDE InvestigatorsCardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med.2012; 367( 23): 2204– 2213.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry

Allocation: Concealed

Setting: Outpatient (any)