Statin use in a "real-world" clinical setting: aggressive lipid lowering compared with usual care in the Aggressive Lipid-Lowering Initiation Abates New Cardiac Events (ALLIANCE) trial.

Clinical trials that incorporate elements of "real-world" experience are of great value to practicing physicians. Using a trial design adapted to approximate clinical settings, the Aggressive Lipid-Lowering Initiation Abates New Cardiac Events (ALLIANCE) trial compared a focused treatment strategy using atorvastatin with usual medical care. Patients eligible for study participation were predefined based on diagnosis codes for coronary heart disease from US managed care database records; 66% of these patients were taking lipid-lowering medications at study entry. In contrast to standard clinical trials, ALLIANCE maintained a real-world environment by limiting the interactions of investigators with patients after dose titration of aggressive treatment to a low-density lipoprotein (LDL) cholesterol goal < 80 mg/dL (2.1 mmol/L) or maximum atorvastatin dose of 80 mg/day. After 51.5 months of follow-up, the study showed that aggressive treatment with atorvastatin was associated with significantly lower LDL cholesterol levels (147 mg/dL [3.8 mmol/L] to 95 mg/dL [2.5 mmol/L]) over usual care (146 mg/dL [3.8 mmol/L] to 111 mg/dL [2.9 mmol/L]). This greater reduction in LDL cholesterol was accompanied by improved outcomes in the composite primary end point of cardiovascular events (-17% with atorvastatin vs. usual care; P = 0.02) and particularly in the end point of nonfatal myocardial infarction (-47% with atorvastatin vs. usual care; P = 0.0002). No safety difference was noted between the 2 treatment groups. These results indicate that usual-care treatment was not equivalent to targeted statin therapy, even in a trial conducted to minimize potential bias owing to traditional patient selection and trial design methods.