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Atorvastatin Calcium Tablets (Lipitor) to Reduce Risk for MI in
On April 24, Health Canada approved an expanded indication for atorvastatin calcium (Lipitor tablets, Pfizer Canada, Inc), allowing its use to reduce the risk for myocardial infarction in adult patients without clinically evident coronary heart disease (CHD) but having risk factors for the condition such as prior myocardial infarction (MI).
The approval was based in part on data from the Treating to New Targets (TNT trial), in which the effect of 80 mg/day of atorvastatin on the reduction of cardiovascular (CV) events was assessed in 10,001 patients (94% white, 81% men, 38% aged ≥ 65 years) with clinically evident CHD. The patients had received a run-in regimen of atorvastatin, 10 mg/day, for 8 weeks, which lowered their mean low-density lipoprotein (LDL) cholesterol level from 152 to 98 mg/dL.
Patients were randomized to continue with the 10-mg/day dose or to receive 80 mg/day for a median duration of 4.9 years. At the end of the study, those in the high- vs the low-dose group had a significantly lower mean LDL cholesterol level (77 vs 101 mg/dL).
Results showed that the time to first occurrence of major CV events was significantly lower in patients receiving atorvastatin 80 vs 10 mg/day (8.7% vs 10.9%), representing a 2.2% absolute risk reduction and 22% relative risk reduction. Overall risk reduction was not affected by age or sex.
Further analysis revealed that the reduction was driven by significant decreases in the rate for nonfatal, nonprocedure-related MI (hazard ratio, [HR], 0.78; 95% CI, 0.66 - 0.93) and fatal/nonfatal stroke (HR, 0.75; 95% CI, 0.59 - 0.96), but not CHD death (HR, 0.80; 95% CI, 0.61 - 1.03) or resuscitated cardiac arrest (HR, 0.96; 95% CI, 0.56 - 1.67).
Although the overall frequency of treatment-related adverse events was similar between groups, patients receiving 80 mg vs 10 mg of atorvastatin daily were more likely to have serious adverse events (1.8% vs 1.4%) and to discontinue therapy due to adverse events (9.9% vs 8.1%) during the 4.9-year period. The rate for persistent transaminase elevations (≥ 3 times the upper limit of normal) was 1.3% in the 80-mg/day group vs 0.2% in patients receiving 10 mg/day of atorvastatin.
The expanded indication was previously approved by the US Food and Drug Administration (FDA). Other FDA-approved uses for atorvastatin include its adjunctive use with diet to treat certain dyslipidemias; to reduce the risk for MI, stroke, revascularization procedures, and angina in patients without CHD but having multiple risk factors for the condition; to reduce the risk for MI and stroke in patients with diabetes mellitus and no clinically evident CHD but having multiple risk factors for the condition; and to reduce the risk for nonfatal MI, fatal/nonfatal stroke, revascularization procedures, congestive heart failure hospitalization, and angina in patients with clinically evident CHD.
In Canada, atorvastatin was previously approved for adjunctive use with diet and lifestyle measures to treat certain dyslipidemias; to reduce the risk for MI in adult hypertensive patients without clinically evident CHD but at least 3 additional risk factors (eg, age, smoking, and type 2 diabetes); and to reduce the risk for MI and stroke in adult patients with type 2 diabetes mellitus and hypertension without clinically evident CHD but with other risk factors such as age, albuminuria, or smoking.