| Abstract |
Background:
Data suggest that atorvastatin may have nephroprotective effects, possibly
as a result of direct vascular effects.The TNT study showed that intensive
lipid-lowering therapy with atorvastatin (ATV)80 mg/day provides significant
clinical benefit beyond that afforded by treatment with ATV 10 mg/day
in patients with stable CHD.The current post hoc analysis of the TNT study
investigated how intensive lipid lowering with ATV 80 mg affected renal
function compared with ATV 10 mg in this population.
Methods: 10,001 patients with clinically evident CHD, with LDL-C
levels of <130 mg/dL (3.4 mmol/L) on ATV 10 mg/day were randomized
to double-blind therapy with either ATV 10 mg/day or 80 mg/day. Patients
were followed for a median of 4.9 years. Creatinine clearance (CrCl),
calculated from the Cockroft-Gault formula, was compared at baseline (following
8 weeks ' ATV 10 mg/day) and at the end of follow-up using a last observation
carried forward analysis in the 7965 patients with a baseline and at least
one post-baseline creatinine measurement.
Results: Mean calculated CrCl was 78.8 and 77.5 ml/min at baseline
in the ATV 10 mg and 80 mg groups, respectively, with a mean difference
between the groups of 1.1 ml/min (95%CI =0.31,1.89;p=0.006). At the end
of follow-up, mean CrCl was increased by 1.1 ml/min in the ATV 10 mg group
and by 2.7 ml/min in the ATV 80 mg group. The difference between treatment
groups in mean change (1.6 ml/min;95%CI =1.06,2.05) and mean percent change
from baseline (2.1%;95%CI =1.49,2.74) were both highly significant (p<0.0001).
In the ATV 80 mg arm, CrCl improved to >60 ml/min in significantly
more patients and declined to <60 ml/min in significantly fewer patients
than in the ATV 10 mg arm. There were no interactions with center, race,
age, or gender. Blood pressure control was similar between the 2 groups.
Both treatments were well tolerated.
Conclusions: Both ATV 10 mg and 80 mg blunted the expected decline
in renal function over the 5 years of the TNT study. In addition to improved
lipid control and further reductions in major cardiovascular events, intensive
treatment with ATV 80 mg resulted in a significant improvement in renal
function over that of ATV 10 mg in patients with stable CHD.
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