Prospective Evaluation of Proteinuria and Renal Function in Diabetic (and Nondiabetic) Patients With Progressive Renal Disease - PLANET I and PLANET II

Jul 19, 2010
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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:
AstraZeneca
Date Presented:
01/01/2010
Date Updated:
07/19/2010
Original Posted Date:
07/19/2010
References

Description:

The goal of the trials was to evaluate treatment with atorvastatin compared with rosuvastatin among diabetic patients (PLANET I) and nondiabetic patients (PLANET II) with hypercholesterolemia and moderate proteinuria.

Hypothesis:

Rosuvastatin would be more effective in preventing urinary protein excretion.

Study Design

  • Blinded
  • Parallel
  • Randomized

Patient Populations:

Patients at least 18 years of age with:

  • Moderate proteinuria (urinary protein/creatinine ratio 500-5000 mg/g)
  • Hypercholesterolemia (low-density lipoprotein cholesterol ≥90 mg/dl)
  • Use of angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker for ≥3 months before screening

Exclusions:

  • Severe renal disease (eGFR <40 ml/min/1.73 m2)
  • Glycated hemoglobin >1%
  • Statin intolerance
  • Homozygous familial hypercholesterolemia or type III hyperlipoproteinemia
  • Liver disease (alanine transaminase >2 x upper limit of normal)

Primary Endpoints:

  • Change in urinary protein/creatinine ratio from baseline to week 52

Secondary Endpoints:

  • Change in urinary protein/creatinine ratio from baseline to week 26
  • Change in urinary albumin/creatine ratio from baseline to weeks 26 and 52
  • Change in eGFR from baseline to weeks 26 and 52
  • Change in lipid levels from baseline to week 52

Drug/Procedures Used:

PLANET I: Diabetic patients with hypercholesterolemia and moderate proteinuria were randomized to atorvastatin 80 mg (n = 111), rosuvastatin 40 mg (n = 124), or rosuvastatin 10 mg (n = 118).

PLANET II: Nondiabetic patients with hypercholesterolemia and moderate proteinuria were randomized to atorvastatin 80 mg (n = 80), rosuvastatin 40 mg (n = 87), or rosuvastatin 10 mg (n = 70).

Eight weeks prior to randomization, patients entered a lead-in period when antihypertensive agents were optimized and pre-existing statins were withdrawn. After randomization, patients in the atorvastatin 80 mg and rosuvastatin 40 mg groups received half their assigned dose for 4 weeks to assess tolerability.

Principal Findings:

PLANET I: Overall 353 patients were randomized. The mean age was 57 years, 31% were women, mean body mass index was 32 kg/m2, and mean estimated glomerular filtration rate (eGFR) was 70.9 ml/min/1.73 m2. Type 2 diabetes was present in 86% and type 1 diabetes in 14%.

Change in high-density lipoprotein at 52 weeks: -2.41 mg/dl in the atorvastatin 80 mg group, 2.82 mg/dl in the rosuvastatin 40 mg group, 4.94 mg/dl in the rosuvastatin 10 mg group.

The change in urinary protein/creatinine ratio from baseline to week 52 decreased by 12.6% in the atorvastatin 80 mg group (p = 0.033), <5% in the rosuvastatin 40 mg (p = NS), and <5% in the rosuvastatin 10 mg group (p = NS). Effects were similar from baseline to week 26.

Change in eGFR at 52 weeks: No change in atorvastatin 80 mg group, -7.29 ml/min in the rosuvastatin 40 mg group (p = 0.0002), and -3.70 ml/min in the rosuvastatin 10 mg group (p = 0.0098).

Adverse events were highest in the rosuvastatin 40 mg group: Acute renal failure occurred in five patients and serum creatinine doubling occurred in six patients.

PLANET II: Overall, 237 patients were randomized. The mean age was 48 years, 40% were women, mean body mass index was 28 kg/m2, and mean eGFR was 74.9 ml/min/1.73 m2.

The change in urinary protein/creatinine ratio from baseline to week 52 decreased by 24.1% in the atorvastatin 80 mg group (p = 0.0026), <10% in the rosuvastatin 40 mg (p = NS), and <10% in the rosuvastatin 10 mg group (p = NS). Effects were similar from baseline to week 26.

Change in eGFR at 52 weeks: No change in the atorvastatin 80 mg group, -3.30 ml/min in the rosuvastatin 40 mg group (p = 0.019), and no change in the rosuvastatin 10 mg group.

Interpretation:

Among diabetic and nondiabetic patients with moderate proteinuria, atorvastatin 80 mg appeared to be superior at preventing renal damage. Atorvastatin 80 mg reduced proteinuria, whereas rosuvastatin 10 or 40 mg had no effect. Atorvastatin 80 mg was not associated with reduced renal function, whereas rosuvastatin 40 mg was associated with reduced renal function.

References:

Presented by Dr. Dick de Zeeuw at a late-breaking trial session, XLVII European Renal Association-European Dialysis and Transplant Association Congress; Munich, Germany, June 27, 2010.

Keywords: Fluorobenzenes, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Diabetes Mellitus, Type 2, Acute Kidney Injury, Pyrimidines, Proteinuria, Heptanoic Acids, Creatinine, Hypercholesterolemia, Pyrroles, Body Mass Index, Glomerular Filtration Rate, Sulfonamides


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