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Evaluation of a novel clinical platform for cardiovascular drug development

ABSTRACT: Objectives –To determine whether inflammation biomarkers can be used as indicators of therapeutic response, an exploratory study was performed to ascertain whether short term improvements in risk parameters will have measureable effects on a pre-defined panel of plaque inflammation biomarkers. Methods and Results – Patients (n=121) with peripheral arterial disease were enrolled into one of three sub-studies based upon the presence of hypercholesterolemia, hypertension, or diabetes. Patients were randomized to 6 weeks of drug treatment vs. placebo and underwent catheter excision of atherosclerotic tissue from one extremity at baseline and the contralateral extremity after treatment. Simvastatin 40mg once daily reduced LDL-C by 43% (p<0.01), losartan 50mg once daily reduced diastolic blood pressure by 4 mm Hg (p=0.099), and pioglitazone 30mg once daily reduced serum glucose by 66mg/dL (p=0.008). Despite these effects, there were no consistent treatment effects on a large panel of plaque protein, RNA and lipid biomarkers. Conclusions – Short term treatment with drugs that improve cardiovascular risk parameters did not result in a measureable reduction in the levels of peripheral arterial plaque inflammation biomarkers. Further studies are required to identify biomarkers that are sufficiently predictive to be used to identify drug candidates for testing in large cardiovascular outcome studies. (ClinicalTrials.gov: NCT00720577)

ORGANISM(S): Homo sapiens

PROVIDER: GSE37824 | GEO | 2012/05/16

SECONDARY ACCESSION(S): PRJNA167021

REPOSITORIES: GEO

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Evaluation of a novel clinical platform for cardiovascular drug development

Project description:Objectives M-bM-^@M-^STo determine whether inflammation biomarkers can be used as indicators of therapeutic response, an exploratory study was performed to ascertain whether short term improvements in risk parameters will have measureable effects on a pre-defined panel of plaque inflammation biomarkers. Methods and Results M-bM-^@M-^S Patients (n=121) with peripheral arterial disease were enrolled into one of three sub-studies based upon the presence of hypercholesterolemia, hypertension, or diabetes. Patients were randomized to 6 weeks of drug treatment vs. placebo and underwent catheter excision of atherosclerotic tissue from one extremity at baseline and the contralateral extremity after treatment. Simvastatin 40mg once daily reduced LDL-C by 43% (p<0.01), losartan 50mg once daily reduced diastolic blood pressure by 4 mm Hg (p=0.099), and pioglitazone 30mg once daily reduced serum glucose by 66mg/dL (p=0.008). Despite these effects, there were no consistent treatment effects on a large panel of plaque protein, RNA and lipid biomarkers. Conclusions M-bM-^@M-^S Short term treatment with drugs that improve cardiovascular risk parameters did not result in a measureable reduction in the levels of peripheral arterial plaque inflammation biomarkers. Further studies are required to identify biomarkers that are sufficiently predictive to be used to identify drug candidates for testing in large cardiovascular outcome studies. (ClinicalTrials.gov: NCT00720577) Human peripheral atherosclerosis plaque was extracted from lower extremities, and RNA, lipids and proteins extracted. RNA was analyzed in an Agilent two-color platform.

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