NEW ORLEANS—Two studies conducted exclusively in African Americans demonstrate the efficacy of rosuvastatin in dyslipidemic patients and the life-saving ability of nitric oxide—enhancing therapy in heart failure. The studies were presented at the American Heart Association Scientific Sessions 2004.
In the African American Rosuvastatin Investigation of Efficacy and Safety (ARIES) trial, 774 African American adults with baseline low-density lipoprotein (LDL) cholesterol levels of 160 to 300 mg/dL were randomly assigned to rosuva-statin, 10 or 20 mg/day, or atorva-statin, 10 or 20 mg/day, for 6 weeks. Sixty-five percent of the ARIES population were women and 24.3% had diabetes.
“We saw greater efficacy of rosuvastatin in mg-equivalent doses compared with atorvastatin,” said principal investigator Keith C. Ferdinand, MD, medical director, Heartbeats Life Center, New Orleans.
In the study, 10 mg of rosuva-statin produced a 37.1% reduction in LDL cholesterol, compared with a 31.8% reduction produced by 10 mg of atorvastatin. At 20 mg, rosuva-statin reduced LDL cholesterol by 45.7% and atorvastatin reduced it by 38.5%. Furthermore, high-density lipoprotein (HDL) cholesterol was increased more with rosuva-statin, with the difference being significant between 10 mg of rosuva-statin and 20 mg of atorvastatin ( 7.0% versus 3.7%; P < .001), said Dr. Ferdinand.
The percentage of patients who reached their Adult Treatment Panel III LDL cholesterol goal was examined by risk levels (low, medium, or high). More patients at each risk level reached their goal with rosuva-statin 20 mg than with atorvastatin 20 mg, with 63% of high-risk patients treated with the 20 mg dose of rosuvastatin reaching their goal compared with 27% of high-risk patients treated with atorvastatin, 20 mg.
There were no cases of myopathy in either treatment group and no elevations in liver enzymes three times or greater above the upper limit of normal. “There were no cases of patients who had acute renal failure and no increase in serum creatinine; there was no evidence of any kidney disease or difference in new-onset proteinuria between the arms,” said Dr. Ferdinand.
In the African-American Heart Failure Trial (A-HeFT), 1,050 self-identified African American patients with New York Heart Association functional class III or IV heart failure were randomly assigned to a fixed dose of isosorbide dinitrate/
hydralazine (20 mg/37.5 mg) or placebo in addition to standard heart failure treatments, including neurohormonal blockers.
Isosorbide dinitrate exerts a va-
sodilatory effect by donating nitric oxide or forming related components, said lead investigator Anne L. Taylor, MD, associate dean for faculty affairs, University of Minnesota, Minneapolis. Hydralazine is an antioxidant that may protect against degradation of nitric oxide induced by oxidative stress.
The study was stopped early owing to a significant survival benefit in the group assigned to the study drug, she said. At a mean of 10 months, a 43% improvement in survival was found in patients assigned to active treatment (P = .01). During this time, 6.2% of patients assigned to isosorbide dinitrate/
hydralazine died compared with 10.2% allocated to placebo (P = .02). Isosorbide dinitrate/hydralazine was associated with a 33% reduction in the rate of first hospitalization for heart failure (P = .001) and a significant improvement in quality of life scores (P = .02).
Nitric oxide bioavailability is impaired in African Americans compared with non-African Americans, noted Dr. Taylor. “Nitric oxide enhancement, which we think is the mechanism of action of this drug, is a new and potentially highly effective treatment for heart failure, especially in African Americans,” she said.