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• RAAS Modulation: Novel Strategies for Reducing Cardiovascular Risk



RAAS Modulation:  Novel Strategies for Reducing Cardiovascular Risk

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RAAS Modulation: 
Novel Strategies for Reducing Cardiovascular Risk Epidemiology/Guideline 
Update: CHD risk rises sharply in middle age CV disease: Leading cause of death in AmericansObesity and diabetes among US adults:Growing prevalence ACC/AHA 2002 Guideline Update for Management of Patients with Chronic Stable Angina: Asymptomatic patients ACP recommendations for ACEI in chronic stable angina or asymptomatic CADRAAS: Central Role in the Pathogenesis ofCardiovascular Disease RAAS: Sites of intervention with ACEIs, ARBs RAAS: Other potential sites of intervention Ang II and mechanisms of atherosclerosis PERTINENT: ACE inhibition  NO via  eNOS activity AT1 receptor blockade improves flow-mediated vasodilation Ang II and mechanisms of atherosclerosis ACE inhibition reduces oxidative stress and inflammation Ang II and mechanisms of atherosclerosis AT1, LOX-1 receptor cross-talk promotes adhesion molecule expression: Interaction between RAAS and dyslipidemia Ang II upregulates LOX-1 expression via lipoxygenase pathway Ang II and mechanisms of atherosclerosis HOPE: Dose-dependent effects of ramipril on LV mass and function LIFE: Greater reduction in LV mass with angiotensin receptor blockade 
vs beta-blockade Ang II and mechanisms of atherosclerosis PAI-1 release: Differing effects of ACEinhibition vs AT1 receptor blockade Change in PAI-1 antigen levels: Differing effects of ARBs tPA release: Differing effects of ACEinhibition vs AT1 receptor blockade Antiatherosclerotic effect of RAAS modulation: Clinical and experimental evidence ARB blunts MMP expression in human carotid plaques: Potential role in plaque stabilization Role of RAAS 
Modulation in CAD Patients ACE inhibition in CAD: Short-term trials in acute MI ACE inhibition in CAD: Long-term trials in post-MI LV dysfunction and HF Aldosterone blockade and AT1 receptor blockade: Trials in post-MI/LV dysfunction or HF HOPE, QUIET, EUROPA, PEACE: Primary outcomes HOPE, EUROPA: Consistency of treatment benefit HOPE, EUROPA: Concomitant CV therapy PEACE: Prevention of Events with Angiotensin Converting Enzyme inhibition PEACE: Primary outcome ACEI outcome trials in CAD patients without HF ACEI outcome trials in CAD patientswithout HF: Key baseline characteristics ACEI outcome trials in CAD patients without HF: CV therapies at entry/during study ACEI outcome trials in CAD patients without HF: BP at entry/during study ACEI outcome trials in CAD patients without HF: Differences in baseline CV risk ACEI outcome trials in CAD patients without HF: Annualized all-cause mortality— placebo vs general population ACEI outcome trials in CAD patients without HF: Annualized CV mortality— placebo vs general population ACEI outcome trials in CAD patients without HF: Cumulative evidence ACEI outcome trials in CAD patients without HF: Totality of trial evidence CAMELOT: Trial of BP reduction with ACEI or CCB in CAD patients without HF CAMELOT: Reduction in primary outcome with amlodipine and enalapril CAMELOT: Clinical implications ACEI outcome trials in CAD patients without HF: Clinical implications Factors that may lead to divergent results in ACEI trials Are all ACEIs the same:                                                                                          Survival post-MI by ACEI at discharge
Ongoing major outcomes trials of RAAS modulation RAAS Modulation in Patients With Diabetes MICRO-HOPE, PERSUADE: ACEI in high-risk patients with diabetes MICRO-HOPE, PERSUADE: Primary outcome MICRO-HOPE, PERSUADE: Consistency of benefit MICRO-HOPE: ACEI improves renal and CV outcomes in type 2 diabetes LIFE: Comparison of treatment effects in overall population vs with diabetes Effects of ARBs in type 2 diabetes: Renal and CV outcomes Impact of Lifestyle Changeand Pharmacologic Therapy
on Diabetes/CV
Prevention Strategies INTERHEART: Positive impact of lifestyle factors on acute MI Randomized controlled trials of Mediterranean-style diets in CAD patients:  Fatal/nonfatal CV events Prospective cohort studies of Mediterranean-style diets:  Mortality Decrease in mortality with Mediterranean diet: EPIC–elderly prospective cohort study Mediterranean diet reduces the metabolic syndrome Diabetes Prevention Program: Impact of lifestyle intervention or metformin Diabetes Prevention Program: Impact of PPAR agonist Diabetes Prevention Program: Impact of lifestyle intervention or metformin on development of metabolic syndrome HOPE/HOPE-TOO: Prevention of diabetes CV pharmacotherapy: Impact on newly diagnosed diabetes Ongoing trials of diabetes prevention with RAAS modulation Peri-Interventional Care
of CAD Patients:
Optimal Discharge Strategies ACC/AHA recommendations: Discharge medical therapy after STEMI ACC/AHA recommendations: Dischargetherapy after unstable angina/NSTEMI Opportunity for optimizing discharge care Nontarget-lesion events drive adverse outcomes 5 years after PCI Improving long-term outcomes in patients with coronary stents CRUSADE: Variations among hospitals in discharge care CRUSADE: Discharge care in men and women Evidence-based medications in ACS patients: Effect on 6-month mortality Guideline adherence reduces in-hospital mortality Potential impact of CV-protective medication class in post-MI patients
This program was prepared and produced by Medical Education Consultants, LLCSM, Westport, Connecticut, on behalf of the University of Florida College of Medicine.

The editorial content of this program does not necessarily reflect the views or recommendations of the University of Florida College of Medicine, King Pharmaceuticals Inc, and Wyeth Pharmaceuticals, or the publisher.
The reader is advised to consult the full prescribing information for each product prior to use.

© 2005 Medical Education Consultants, LLCSM (MEDCON). All rights reserved.

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