Aggressive Lipid-Lowering Initiation Abates New Cardiac Events - ALLIANCE
The goal of the trial was to evaluate the effect of an aggressive lipid-lowering program using atorvastatin compared with usual care on cardiovascular events in patients with a history of coronary artery disease (CAD) and elevated low-density lipoprotein (LDL) levels in a managed care population.
Treatment with an aggressive lipid-lowering program using atorvastatin will be associated with fewer cardiovascular events compared with usual care in patients with a history of CAD and elevated LDL levels.
Patients Screened: 3,451
Patients Enrolled: 2,442
Mean Follow Up: Mean follow-up 52 months
Mean Patient Age: Mean age 61 years
Age ≥18 years, history of CAD (acute MI >3 months prior, percutaneous transluminal coronary angioplasty >6 months prior, or coronary artery bypass grafting or unstable angina >3 months prior), and LDL 130-250 mg/dl if not on hyperlipidemic medication or LDL 110-200 mg/dl if on hyperlipidemic medication
Time to first cardiovascular event including cardiovascular death, nonfatal MI, cardiac revascularization, resuscitated cardiac arrest, or hospitalization for an acute coronary syndrome
Patients were randomized to either atorvastatin (10-80 mg/day) titrated as needed to reach an LDL cholesterol level of <80 mg/dl or to a maximum dose of 80 mg (n=1,217) or usual care (n=1,225). Usual care patients received treatment as directed by their physicians, including diet, behavior modification, or lipid-lowering medication, and treatment could be changed during the study duration per current recommendations.
The study began in 1995 and ended in 2002. The mean dose in the atorvastatin arm was 40.5 mg/day. Two-thirds of patients were on lipid-lowering medication prior to enrollment in the study.
There was no difference in baseline LDL levels (147 mg/dl each), but the reduction in the final LDL level was greater in the atorvastatin arm compared with usual care (95 mg/dl vs. 110 mg/dl, p<0.001). Target level of LDL cholesterol, as defined by the Adult Treatment Panel III (<100 mg/dl), was reached in 72.4% of patients in the atorvastatin arm and 40.0% of patients in the usual care group (p<0.001). Relative change in total cholesterol was also greater in the atorvastatin arm (-24.1% vs. -15.5%, p<0.001), as were triglycerides (-7.4% vs. -2.4%, p<0.05), but there was no difference in change in high-density lipoprotein (HDL) levels.
The primary composite endpoint of cardiovascular events was lower in the atorvastatin arm (23.7% vs. 27.7%, relative reduction [RR] 17%, p=0.02), as was myocardial infarction (MI) (4.3% vs. 7.7%, RR 47%, p=0.0002) and cardiovascular death (n=43 vs. n=61, p=0.057).
There was no difference in the frequency of serious adverse events (40% in the atorvastatin arm vs. 42% of patients in the usual care arm, p=NS). There were no cases of rhabdomyolysis in either group.
Among patients with a history of CAD and elevated LDL levels in a managed care population, treatment with an aggressive lipid-lowering program with atorvastatin was associated with a reduction in the primary endpoint of cardiovascular events. The trial was designed to evaluate aggressive lipid-lowering with a flexible dosing regimen rather than a lower, fixed dose. At the time of the study initiation, there was limited information and some concern about the safety of high-dose statins.
Koren MJ, et al. Clinical Outcomes in Managed-Care Patients With Coronary Heart Disease Treated Aggressively in Lipid-Lowering Disease Management Clinics. J Am Coll Cardiol 2004;44:1772-9.
Presented by Dr. Michael Koren at the American College of Cardiology Annual Scientific Session, March 2004.
Clinical Topics: Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Prevention, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease, Diet
Keywords: Managed Care Programs, Coronary Artery Disease, Myocardial Infarction, Behavior Therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Heptanoic Acids, Hypercholesterolemia, Angioplasty, Balloon, Coronary, Rhabdomyolysis, Pyrroles, Cholesterol, Diet, Triglycerides, Coronary Artery Bypass
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