The Food and Drug Administration has approved atorvastatin for five new indications in adults with coronary heart disease, based on findings in the Treating to New Targets trial.
The approval, issued in March, was for reducing the risk of nonfatal myocardial infarction, fatal and nonfatal stroke, angina, revascularization procedures, and hospitalization for heart failure, in patients with clinically evident coronary heart disease.
In the Treating to New Targets (TNT) trial, the 80-mg daily dosage of atorvastatin was associated with a significantly greater reduction in the risk of events that make up the five new indications, compared with the 10-mg dose, over a median of almost 5 years in 10,001 patients.
The primary end point was time to occurrence of any of these major cardiovascular events: death resulting from CHD, nonfatal MI, resuscitated cardiac arrest, and fatal and nonfatal stroke. There were 434 such events among those on 80 mg/day, versus 548 such events among those on 10 mg/day, translating to a relative risk reduction of 22%—a highly significant difference. This overall reduction in risk was consistent, regardless of gender or whether patients were younger than age 65 or aged 65 years and older. As for individual events, the rate of nonfatal, non-procedure-related MI and fatal and nonfatal stroke was significantly reduced in the 80-mg/day group, when compared with placebo, but neither CHD death nor resuscitated cardiac arrest was significantly reduced, according to the revised package label for atorvastatin, which is marketed as Lipitor by Pfizer.
The 80-mg/day dose also significantly reduced some secondary end points: the rate of coronary revascularization, angina, and hospitalization for heart failure. The rate of heart failure hospitalization was lower with atorvastatin 80 mg/day, but only in the 8% of patients with a history of heart failure. All-cause mortality was not significantly different in the two groups, according to the drug's revised label. Those on 80 mg of atorvastatin per day had more serious adverse events (2%) and discontinuations because of adverse events (10%) over 5 years, compared with those on the 10-mg dose (1% and 8%, respectively), according to the drug's revised label.
Noting that atherosclerosis is not just a disease of the large coronary arteries, but involves the smaller vessels as well, Dr. Ann Bolger, professor of clinical medicine at the University of California, San Francisco, said in an interview that reducing the lipid burden and reducing inflammation with statins seem to decrease the incidence of cardiovascular events, which usually start at the endothelial level.