Progression of kidney disease in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin versus usual care: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Abstract

Background: Dyslipidemia is common in patients with chronic kidney disease. The role of statin therapy in the progression of kidney disease is unclear.

Study design: Prospective randomized clinical trial, post hoc analyses.

Setting & participants: 10,060 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) stratified by baseline estimated glomerular filtration rate (eGFR): less than 60, 60 to 89, and 90 or greater mL/min/1.73 m(2). Mean follow-up was 4.8 years.

Intervention: Randomized; pravastatin, 40 mg/d, or usual care.

Outcomes & measurements: Total, high-density lipoprotein, and low-density lipoprotein cholesterol; end-stage renal disease (ESRD), eGFR.

Results: Through year 6, total cholesterol levels decreased in the pravastatin (-20.7%) and usual-care groups (-11.2%). No significant differences were seen between groups for rates of ESRD (1.36 v 1.45/100 patient-years; P = 0.9), composite end points of ESRD and 50% or 25% decrease in eGFR, or rate of change in eGFR. Findings were consistent across eGFR strata. In patients with eGFR of 90 mL/min/1.73 m(2) or greater, the pravastatin arm tended to have a higher eGFR.

Limitations: Proteinuria data unavailable, post hoc analyses, unconfirmed validity of the Modification of Diet in Renal Disease Study equation in normal eGFR range, statin drop-in rate in usual-care group with small cholesterol differential between groups.

Conclusions: In hypertensive patients with moderate dyslipidemia and decreased eGFR, pravastatin was not superior to usual care in preventing clinical renal outcomes. This was consistent across the strata of baseline eGFR. However, benefit from statin therapy may depend on the degree of the cholesterol level decrease achieved.

Trial registration: ClinicalTrials.gov NCT00000542.

Figure 1

Randomization and Follow-up of Participants with Valid Baseline Estimated GFR in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

Fig 2

Statin Use and Lipid Levels Over the Course of the Study. Abbreviations: LDL, low-density lipoprotein; HDL, high-density lipoprotein. To convert total cholesterol, LDL-cholesterol, and HDL-cholesterol in mg/dL to mmol/L, multiply by 0.02586. To convert triglycerides in mg/dL to mmol/L, multiply by 0.01129.

Fig 3

Survival curves for kidney disease events - pravastatin versus usual care. Treatment groups by baseline estimated glomerular filtration rate (eGFR) estimates. Panels A–C: all participants (n=10,060). Panels D–F: the subgroup of participants with baseline GFR <60 mL/min/1.73 m² (n=1557). To convert GFR in mL/min/1.73 m² to mL/s/1.73 m², multiply by 0.01667.

Fig 3

Survival curves for kidney disease events - pravastatin versus usual care. Treatment groups by baseline estimated glomerular filtration rate (eGFR) estimates. Panels A–C: all participants (n=10,060). Panels D–F: the subgroup of participants with baseline GFR <60 mL/min/1.73 m² (n=1557). To convert GFR in mL/min/1.73 m² to mL/s/1.73 m², multiply by 0.01667.

Figure 4

Renal Outcomes in the Lipid-Lowering Component of ALLHAT by Treatment Group and GFR Group at Baseline (Relative Risks and 95% Confidence Intervals, 6-Year Rates per 100, and Total Events). To convert GFR in mL/min/1.73 m² to mL/s/1.73 m², multiply by 0.01667.

Figure 5

Estimated GFR (mL/min/1.73 m²) Over the Course of the Study. To convert GFR in mL/min/1.73 m² to mL/s/1.73 m², multiply by 0.01667.