Aliskiren in the Evaluation of Proteinuria in Diabetes - AVOID


The goal of the trial was to evaluate treatment with aliskiren and losartan compared with losartan and placebo in patients with type 2 diabetes, hypertension, and nephropathy.


Aliskiren and losartan will be more effective in preventing the progression of nephropathy.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded

Patients Screened: 1,892
Patients Enrolled: 599
Mean Follow Up: 6 months
Mean Patient Age: 61
Female: 29

Patient Populations:

Patients 18-85 years of age with type 2 diabetes, hypertension, and nephropathy. Nephropathy was defined as a urinary albumin-to-creatinine ratio >300 mg/g or >200 mg/g in patients on medications to block the renin-angiotensin-aldosterone system.


• Nondiabetic kidney disease
• Urinary albumin-to-creatinine ratio >3500 mg/g
• Estimated glomerular filtration rate <30 ml/min/1.73 m2 of body-surface area
• Chronic urinary track infection
• Serum potassium >5.1 mmol/L at the time of randomization
• Severe hypertension
• Major cardiovascular disease in the last 6 months

Primary Endpoints:

Reduction in the ratio of albumin to creatinine at 6 months

Secondary Endpoints:

Change in blood pressure

Drug/Procedures Used:

After a 3-month open-label period, patients were randomized to aliskiren 150 mg daily for 3 months, then aliskiren 300 mg daily for 3 months (n = 301) or placebo for 6 months (n = 298).

Concomitant Medications:

A total of 805 patients began an open-label period during which any renin-angiotension-aldosterone blocking medications were discontinued and losartan 100 mg daily was begun. Patients also received additional antihypertensive medications to achieve a blood pressure to goal <130/80 mm Hg.

At baseline (for aliskiren vs. placebo), the use of insulin and insulin analogues were 53.8% versus 53.0%, biguanides were 48.2% versus 47.3%, sulfonylureas were 37.5% versus 39.9%, thiazolidinediones were 11.0% versus 12.8%, statins were 56.1% versus 56.7%, aspirin was 40.5% versus 42.3%, calcium-channel blockers were 51.2% versus 58.1%, beta-blockers were 34.6% versus 36.2%, thiazide diuretics were 34.2% versus 34.9%, loop diuretics were 25.9% versus 28.5%, alpha-blockers were 15.3% versus 11.4%, and centrally acting agents were 8.3% versus 5.7%, respectively.

Principal Findings:

At baseline, the estimated glomerular filtration rate was 68.5 ml/min/1.73 m2 of body-surface area compared with 66.8 ml/min/1.73 m2 of body-surface area, glycated hemoglobin was 8.0% versus 7.9%, and systolic blood pressure was 135 mm Hg versus 134 mm Hg, respectively for aliskiren versus placebo.

At 6 months of follow-up, the losartan and aliskiren group had experienced a urinary albumin-to-creatinine ratio reduction of 20% compared with losartan and placebo (p < 0.001). Blood pressure was marginally lower in the losartan and aliskiren group compared with losartan and placebo (2 mm Hg reduction in systolic blood pressure, p = 0.07; 1 mm Hg reduction in diastolic blood pressure, p = 0.08). After adjusting for the change in systolic blood pressure, there was an 18% reduction in the urinary albumin-to-creatinine ratio favoring losartan and aliskirin (p = 0.002). There was no difference in the primary outcome among any of the tested subgroups.

There was no difference in the incidence of any adverse event (66.8% vs. 67.1%) or the incidence of any serious adverse event (9.0% vs. 9.4%), respectively for losartan and aliskiren versus losartan and placebo.


Dual blockade of the renin-angiotensin-aldosterone system with losartan and aliskiren is beneficial in reducing albuminuria among type 2 diabetics with hypertension and nephropathy. Aliskiren, an oral direct inhibitor of renin, also appeared to have a modest blood pressure lowering effect; however, the reduction in albuminuria was preserved after controlling for this change in blood pressure. This is an important finding since many patients who receive angiotensin-receptor blockers or angiotensin-converting-enzyme inhibitors still have progression of renal disease. The 6-month findings of the AVOID study will need to be confirmed with longer-term follow-up.


Parving HH, Persson F, Lewis JB, et al., on behalf of the AVOID study investigators. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med 2008;358:2433-46.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Hypertension

Keywords: Losartan, Follow-Up Studies, Diabetes Mellitus, Type 2, Renin-Angiotensin System, Blood Pressure, Enzyme Inhibitors, Creatinine, Hemoglobin A, Glycosylated, Fumarates, Glomerular Filtration Rate, Hypertension

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