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BRAVER TrialBRAVER Trial

BRBRachial achial AArtery rtery VVascular ascular EEndothelium ndothelium RReactivity Studyeactivity Study

A substudy of PROVE IT-TIMI 22A substudy of PROVE IT-TIMI 22

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BRAVER: Study design

Objective: – Evaluate time course of improvement in endothelialfunction 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;96:1207-13.

*≤200 mg/dL if on long-term lipid-lowering drugs

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Dupuis J et al. Am J Cardiol. 2005;96:1207-13.

• 32% reduction in LDL-C with atorvastatin 80 mg (P < 0.001 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 dilationNMD = Endothelium-independent sublingual nitroglycerin-mediated dilation

BRAVER: Results

BRachial Artery Vascular Endothelium Reactivity

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BRAVER: Clinical implications

Dupuis J et al. Am J Cardiol. 2005;96:1207-13.

• 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