VBWG BRAVER Trial BRachial Artery Vascular Endothelium Reactivity Study A substudy of PROVE IT-TIMI 22

VBWG BRAVER: Study design Objective: – Evaluate time course of improvement in endothelial function with statin after acute coronary syndromes (ACS) –Compare effects of intense vs moderate statin therapies on vascular reactivity Design: Randomized double-blind 2 x 2 factorial design Population: N = 50 with ACS; total cholesterol ≤240 mg/dL* Treatment: Atorvastatin 80 mg (n = 24) or pravastatin 40 mg (n = 26) Outcome: Amount of change in brachial artery reactivity measured by high-resolution ultrasound at days 2, 30, and 120 BRachial Artery Vascular Endothelium Reactivity Substudy of PROVE IT-TIMI 22 Dupuis J et al. Am J Cardiol. 2005;96: *≤200 mg/dL if on long-term lipid-lowering drugs

VBWG Dupuis J et al. Am J Cardiol. 2005;96: % reduction in LDL-C with atorvastatin 80 mg (P < vs baseline) vs no reduction with pravastatin 40 mg after 4 months Similar reductions in C-reactive protein (CRP) in both treatment groups 27% increase in FMD; 24% increase in NMD (P <0.05 vs baseline), with no difference between treatment strategies Changes in FMD, lipid levels, and CRP were not correlated FMD and NMD remained unchanged in patients treated with statins prior to ACS (n = 15) FMD = Endothelium-dependent flow-mediated dilation NMD = Endothelium-independent sublingual nitroglycerin-mediated dilation BRAVER: Results BRachial Artery Vascular Endothelium Reactivity

VBWG BRAVER: Clinical implications Dupuis J et al. Am J Cardiol. 2005;96: Statin therapy soon after ACS improves endothelium- dependent and endothelium-independent vascular reactivity Improvements observed after 4 months of treatment Results comparable despite differing intensities of treatment Power to detect differences between atorvastatin and pravastatin groups was limited; findings add to growing evidence that improvement in vascular reactivity with statins is independent of the importance of lowering cholesterol Lack of improvement in subjects previously using statins suggests new statin initiation is needed for major improvements in vascular reactivity after ACS BRachial Artery Vascular Endothelium Reactivity