August 26th, 2012
First Detailed Look At Why Aliskiren Failed To Gain ALTITUDE
Last December the once-promising direct renin inhibitor aliskiren (Rasilez, Tekturna) suffered a fatal setback with the early termination of the ALTITUDE trial. The trial was stopped when the Data Monitoring Committee (DMC) found an increased risk for non-fatal stroke, renal complications, hyperkalemia, and hypotension in patients taking aliskiren after 18-24 months.
At the ESC in Munich ALTITUDE investigator Hans-Henrik Parving presented the first detailed but preliminary results from the trial, which compared aliskiren to placebo in 8,561 type 2 diabetics at high risk for cardiovascular and renal complications already receiving single RAAS blockade.
After 32 months of followup, there was no significant difference between the two groups in the composite endpoint: CV death, resuscitated death, MI, stroke, unplanned hospitalization for heart failure, onset of end-stage renal disease, or doubling of baseline creatinine. However, Parving noted that the numbers went in the wrong direction for aliskiren, including a trend suggesting more strokes associated with the treatment drug:
- Composite endpoint: 17.9% for aliskiren vs. 16.8% for placebo (HR, 1.08; 95% CI, 0.98-1.20; P=0.142)
- Stroke: 3.4% for aliskiren vs. 2.8% for placebo (HR 1.25; 95% CI, 0.98-1.60; P=0.70)
Aliskiren-treated patients also had higher potassium levels and were more likely to develop hyperkalemia, hypotension, and diarrhea.