TIMI Study Group， Cardiovascular Division， Department of Medicine， Brigham and Women’s Hospital， Harvard Medical School， Boston， Massachusetts， USA. rgiugliano@partners.org
Abstract
OBJECTIVES: This study sought to determine whether the benefit of intensive lipid-lowering therapy (LLT) is dependent on baseline low-density lipoprotein cholesterol (LDL-C).
BACKGROUND: Aggressive LDL-C reduction with statins improves cardiovascular outcomes in acute and chronic coronary heart disease (CHD). The importance of baseline LDL-C is unclear.
METHODS: We compared 2-year composites of death， myocardial infarction (MI)， unstable angina， revascularization >30 days， and stroke (primary end point)， and CHD death， MI， and revascularization >30 days (secondary end point) in 2，986 statin-na?ve patients with recent acute coronary syndrome (ACS) randomized to atorvastatin 80 mg versus pravastatin 40 mg in the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) study stratified by quartiles of baseline LDL-C. Multivariable models assessed whether the treatment benefit was dependent on baseline LDL-C.
RESULTS: A significant reduction in the hazards of the primary (hazard ratio [HR]: 0.63， 95% confidence interval [CI]: 0.47 to 0.85， p = 0.002) and secondary (HR: 0.57， 95% CI: 0.42 to 0.79， p = 0.001) end points occurred in patients within the highest quartile (>132 mg/dl) of baseline LDL-C treated with atorvastatin 80 mg. The benefit of intensive therapy progressively declined as baseline LDL-C decreased. The lowest quartile (LDL-C < or =92 mg/dl) experienced similar rates of the primary (HR: 0.93， 95% CI: 0.69 to 1.25， p = 0.63) and secondary (HR: 0.98， 95% CI: 0.71 to 1.35， p = 0.89) end points. Adjusted interaction tests between treatment and highest versus lowest baseline LDL-C quartile were significant for the primary and secondary end points (p = 0.03 and p = 0.007， respectively). Analyzing baseline LDL-C as a continuous variable， atorvastatin 80 mg was associated with improved outcomes provided the baseline LDL-C was >66 mg/dl.
CONCLUSIONS: A progressive reduction in the benefit of intensive LLT with atorvastatin 80 mg over pravastatin 40 mg occurred in statin-na?ve ACS patients as baseline LDL-C declined.