In its short lifespan the direct renin inhibitor aliskiren (a.k.a., Rasilez or Tekturna) rapidly declined from being a highly promising, first-of-its kind drug to a major failure. The death blow was struck last December with the early termination of the ALTITUDE trial, after the data and safety monitoring committee found an increased risk in patients taking aliskiren. Now the final results of the Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints have been presented at Kidney Week 2012 in San Diego and simultaneously published in the New England Journal of Medicine.
8,561 type 2 diabetics at high risk for cardiovascular and renal complications already receiving an ACE inhibitor or an angiotensin-receptor blocker were randomized to receive aliskiren or placebo. The primary outcome of a cardiorenal event (CV death, resuscitated death, MI, stroke, unplanned hospitalization for heart failure, onset of end-stage renal disease or doubling of baseline creatinine) occurred more often in the aliskiren group, although this difference did not achieve statistical significance:
- 18.3% for aliskiren versus 17.1% for placebo (hazard ratio, 1.08; 95% CI, 0.98-1.20; P=0.12).
A similar trend was observed for just cardiovascular outcomes:
- 13.8% versus 12.6%, respectively (hazard ratio, 1.11; 95% CI, 0.99-1.25; P=0.09)
Compared with placebo, patients on aliskiren had lower blood pressure and a greater reduction in the urinary albumin-to-cretinine ratio. But there was also a significantly higher risk of hyperkalemia (39.1% versus 29.9%; P<0.001) and hypotension (12.1% versus 6.3%, p<0.001).
The authors concluded that the addition of aliskiren to standard therapy in high risk type 2 diabetics “is not supported by these data and may even be harmful.” The result of ALTITUDE, they write, “underscores the need to go beyond surrogate biomarkers and obtain risk-benefit data from clinical end-point trials to better inform clinical decisions.”