High-Dose Statin Therapy Has Expanded Benefits

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ATLANTA—The benefits of intensive statin therapy in patients with coronary heart disease (CHD) or who are at risk for it extend to patients who also have CKD, investigators reported here at the 59th annual scientific session of the American College of Cardiology.

The findings come from subpopulations with both CHD and CKD who were enrolled in two large randomized controlled trials of statin therapy—the Treating to New Targets (TNT) study and the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER).

In TNT, 10,001 patients with CHD were recruited to compare the efficacy of 10 mg/day and 80 mg/day of atorvastatin over an average of five years. In the primary study, a 22% relative reduction in the occurrence of a first major cardiovascular event (the primary end point) was observed in patients assigned to 80 mg of atorvastatin versus 10 mg.

The substudy described here involved 1,859 high-risk CHD patients who also had metabolic syndrome and CKD, defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2.

The combination of CKD and metabolic syndrome was associated with a near doubling of risk for future cardiovascular events irrespective of therapy when compared with those with neither CKD nor metabolic syndrome, said Prakash Deedwania, MD, lead investigator of the TNT substudy and Professor of Medicine at the University of California-San Francisco School of Medicine.

During the five-year course of the study, major cardiovascular events occurred in 8.8% of the high-dose patients with CKD and metabolic syndrome compared with 13.2% of such patients assigned the lower dose, which translated into a significant 35% reduction in relative risk with high-dose therapy, he said.

The data also suggest improvement in kidney function with high-dose atorvastatin. The 10 mg dose of atorvastatin resulted in a significant 1.5 mL/min/1.73 m2 increase in eGFR from baseline versus a 3 mL/min/1.73 m2 increase with the 80 mg dose. The improvement in eGFR with 80 mg of atorvastatin compared with the lower dose was significant.

In a separate subanalysis of 954 patients in TNT who had both CHD and CKD and were obese, the higher dose of atorvastatin was associated with a significant 33% reduction in the risk of major cardiovascular events compared with the lower dose.

In the JUPITER trial, more than 18,000 subjects with unremarkable levels of low-density lipoprotein cholesterol but elevated levels of C-reactive protein were randomized to rosuvastatin 20 mg/day or placebo. After 12 months, the study revealed a significant 44% reduction in the risk of a primary end point—a composite of heart attack, stroke, hospitalization for unstable angina, the need for arterial revascularization, or confirmed cardiovascular death—among those assigned to rosuvastatin.

When investigators focused on the subset of 3,267 patients with CKD (eGFR below 60 mL/min/1.73 m2), they found that those assigned to rosuvastatin had a significant 45% relative reduction in the risk of achieving one of the primary end points in the study and a significant 44% reduction in all-cause mortality.

The cardiovascular benefit observed with rosuvastatin occurred despite only marginal improvement in eGFR among all patients randomized to rosuvastatin, said lead investigator Paul Ridker, MD, Professor of Medicine at Harvard Medical School in Boston, where he also is Director of the Center for Cardiovascular Disease Prevention at the Brigham and Women's Hospital. Overall, patients with CKD had a 54% increased risk of experiencing an end point event compared with subjects who did not have CKD.

He and his colleagues said the results “support guidelines from the American Heart Association and the National Kidney Foundation to provide more aggressive cardiovascular prevention efforts among those with reduced renal function.”

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