By Kristina Rebelo
SAN DIEGO -- November 4, 2009 -- Atorvastatin improves dyslipidaemia in patients with coronary heart disease (CHD), and may even be renoprotective, according to study results released at the American Society of Nephrology (ASN) Renal Week 2009. This improvement would reduce potential additional cardiovascular events, which are common with worsening renal function in patients with and without chronic kidney disease.
"Worsening renal function has been associated with an increase in cardiovascular events," explained lead investigator James Shepherd, MB, CBH, PhD, University of Glasgow, Glasgow, United Kingdom, speaking at a poster presentation here on October 30. "The effect of improving renal function on cardiovascular events, to our knowledge, has not previously been examined."
The Treating to New Targets (TNT) trial examined 10,001 patients aged 35 to 75 years with clinically evident CHD -- defined as myocardial infarction (MI), previous or present angina with atherosclerotic CHD, or a history of a previous coronary revascularisation procedure. Intensive lipid lowering with atorvastatin 80 mg was associated with a reduction in cardiovascular risk compared with atorvastatin 10 mg in patients; a dose-dependent improvement in kidney function was also observed.
The goal of this study, a post hoc analysis of the TNT trial, was to examine the relationship between the change in eGFR from baseline to study conclusion and, also, to examine the risk of major cardiovascular events. The estimated glomerular filtration rate (eGFR) of patients assigned to atorvastatin 80 mg increased by an average of 5.2 mL/min/1.73 m2 compared with an improvement of 3.5 m/L/min/1.73 m2 in the group receiving atorvastatin 10 mg.
After an 8-week, open-label therapy session with atorvastatin 10 mg, patients were randomised to double-blind therapy with either atorvastatin 10 or 80 mg. Each was followed for occurrence of major cardiovascular events for a median of 4.9 years.
Of the 9,656 patients with complete renal data, 156 had a major cardiovascular event before follow-up eGFR assessment, and were subsequently excluded. Quartiles comprising the 9,500 remaining patients represented a decrease in eGFR (Q1, -7.3 mL/min/1.73 m2), no change in eGFR (Q2, 1.6 mL/min/1.73 m2), and progressive increases in eGFR (Q3, 7.2 mL/min/1.73 m2; Q4, 15.8 mL/min/1.73 m2).
Patients in Q3 and Q4 were at significantly lower risk of major cardiovascular events compared with Q1 (both P < .0001); patients in Q2 were at a higher risk of major cardiovascular events compared with Q1 (P = .0010).
Two separate analyses of the TNT study were performed: one was based on clinical classification and the other was a quartile analysis of change in eGFR demonstrating a marked reduction in myocardial infarction, stroke, and CHD death in those patients with CHD who had improvement in renal function with atorvastatin.
"In TNT, the more intensive statin therapy resulted in greater benefit on improvement of kidney function, irrespective of the level of kidney function at baseline," Dr. Shepherd concluded.
Funding for this study was provided by Pfizer Inc.
[Presentation title: Improvement in Estimated Glomerular Filtration Rate With Atorvastatin Predicts Reduced Cardiovascular Risk: The Treating to New Targets (TNT) Study. Abstract F-PO1118]
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