Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints - ALTITUDE

Jan 24, 2013
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Novartis
Date Presented:
01/01/2012
Date Published:
01/01/2012
Date Updated:
01/24/2013
Original Posted Date:
01/24/2013
References

Description:

The goal of the trial was to evaluate treatment with the direct renin inhibitor aliskiren compared with placebo among patients with type 2 diabetes, renal dysfunction, cardiovascular disease, or both.

Hypothesis:

Aliskiren will prevent adverse events.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Patients at least 35 years of age with type 2 diabetes, and microalbuminuria, macroalbuminuria, or cardiovascular disease and treated with an ACE inhibitor or ARB

Primary Endpoints:

  • Death or cardiac arrest with resuscitation,
  • Nonfatal myocardial infarction,
  • Nonfatal stroke,
  • Heart failure hospitalization,
  • End-stage renal disease,
  • Death attributable to kidney failure or need for dialysis with no dialysis or transplant available, or
  • Creatinine value double baseline value

Drug/Procedures Used:

Patients with type 2 diabetes, renal dysfunction, cardiovascular disease, or both and treated with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) were randomized to aliskiren 300 mg daily (n = 4,274) versus placebo (n = 4,287).

Principal Findings:

Overall, 8,561patients were randomized. The mean age was 65 years, 33% were women, 13% were current smokers, mean body mass index was 30 kg/m2, mean systolic blood pressure was 137 mm Hg, mean glycated hemoglobin was 7.8%, and mean glomerular filtration rate was 57 mmL/min 1.73 m2.

The independent Data and Safety Monitoring Committee terminated the trial early due to concern about an increase in adverse events with aliskiren. At a median follow-up of 32.9 months, the primary outcome had occurred in 18.3% of the aliskiren group versus 17.1% of the placebo group (p = 0.12).

Individual outcomes for aliskiren vs. placebo:

- All-cause death: 8.8% vs. 8.4% (p = 0.42)
- Cardiovascular death: 5.8% vs. 5.0% (p = 0.12)
- Resuscitated sudden death: 0.4% vs. 0.2% (p = 0.04)
- Myocardial infarction: 3.4% vs. 3.3% (p = 0.72)
- Stroke: 3.4% vs. 2.8% (p = 0.11)
- Unplanned hospitalization for heart failure: 4.8% vs. 5.1% (p = 0.56)
- Doubling of baseline serum creatinine: 4.9% vs. 5.1% (p = 0.75)
- Onset of end-stage renal disease or renal death: 2.8% vs. 2.6% (p = 0.56)

- Hyperkalemia: 39% vs. 29% (p < 0.001)
- Hypotension: 12% vs. 8.3% (p < 0.001)
- Diarrhea: 9.8% vs. 7.3% (p < 0.001)

Interpretation:

The addition of aliskiren to an ACE inhibitor or ARB among diabetics with renal dysfunction was not beneficial. Adverse outcomes were similar or numerically higher with aliskiren compared with placebo. Preliminary studies had shown an improvement in surrogate outcomes from the addition of aliskiren to an ACE inhibitor or ARB. The use of this drug combination in this patient population cannot be recommended.

References:

Parving HH, Brenner BM, McMurray JJ, et al., on behalf of the ALTITUDE Investigators. Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes. N Engl J Med 2012;367:2204-13.

Presented by Dr. Hans-Henrik Parving at the European Society of Cardiology Congress, Munich, Germany, August 26, 2012.

Keywords: Myocardial Infarction, Stroke, Renin, Kidney Failure, Chronic, Receptors, Angiotensin, Diabetes Mellitus, Type 2, Diarrhea, Death, Sudden, Hypotension, Blood Pressure, Hyperkalemia, Glycated Hemoglobin A, Drug Combinations, Fumarates, Body Mass Index, Heart Failure, Glomerular Filtration Rate, Hospitalization


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