Baseline low-density lipoprotein cholesterol is an important predictor of the benefit of intensive lipid-lowering therapy: a PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) analysis.

Author(s): Giraldez RR, Giugliano RP, Mohanavelu S, Murphy SA, McCabe CH, Cannon CP, Braunwald E

Affiliation(s): TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. rgiugliano@partners.org

Publication date & source: 2008-09-09, J Am Coll Cardiol., 52(11):914-20.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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-naive 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-naive ACS patients as baseline LDL-C declined. (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 [PROVE IT-TIMI 22]; NCT00382460).