In a trial comparing high-dose atorvastatin with moderate-dose simvastatin in patients with stable coronary heart disease (CHD), the aggressive LDL-lowering strategy offered no significant advantage over the less aggressive strategy in reducing the number of coronary events, said Terje R. Pedersen, MD.
In a trial comparing high-dose atorvastatin with moderate-dose simvastatin in patients with stable coronary heart disease (CHD), the aggressive LDL-lowering strategy offered no significant advantage over the less aggressive strategy in reducing the number of coronary events, said Terje R. Pedersen, MD.
In the trial, known as IDEAL (Incremental Decrease in Clinical Endpoints Through Aggressive Lipid Lowering), high-dose atorvastatin was associated with a nonsignificant 11% reduction in major coronary events after nearly 5 years compared with low-dose simvastatin.
In IDEAL, 8,888 patients with stable CHD were randomized to atorvastatin 80 mg/d or simvastatin 20 mg/d, which could be titrated to 40 mg/d if either total cholesterol remained >193 mg/dL or LDL cholesterol remained >115 mg/dL. The regimen of simvastatin used in IDEAL was one established by the Scandinavian Simvastatin Survival Study (4S) to provide significant clinical benefits compared with placebo, Dr Pedersen said.
Several secondary end points favored atorvastatin. Patients randomized to high-dose atorvastatin had a 13% reduction in major cardiovascular events (P=.02), a 16% reduction in any CHD event (P<.001), and a 16% reduction in any cardiovascular event (P<.001).
According to Dr Pedersen, professor of medicine, Ulleval University Hospital, and director of the Center for Preventive Medicine, Oslo, Norway, IDEAL provides some comfort that high-dose statin therapy is safe. In the Treat to New Targets study, high-dose atorvastatin was associated with a trend toward an increase in noncardiovascular mortality compared with moderate-dose pravastatin. In IDEAL, there was a trend toward fewer noncardiovascular deaths in the atorvastatin group. "The 2 trials taken together show that high-dose atorvastatin is not detrimental in any way," Dr Pedersen said.
High-dose statin therapy may not result in fewer deaths in comparison with moderate-dose therapy in clinical trials because mortality in patients with acute coronary syndromes has been reduced dramatically by the widespread use of revascularization procedures, Dr Pedersen said. The mortality rate in IDEAL was only 1% per year, he noted, calling it "outstanding."
He added: "It will be hard for any particular drug to demonstrate further reductions in cardiovascular mortality."
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