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Core Curriculum

• The Renin-Angiotensin-Aldosterone System: Linking New Data and Mechanisms for Cardiovascular Risk Reduction



The Renin-Angiotensin-Aldosterone System:

Download VBWG05CoreCAD-S1.ppt (10 slides - 0.3MB)

The Renin-Angiotensin-Aldosterone System: Contents Scope of the Problem Coronary artery disease: Leading cause of hospitalization in the US Lifetime risk for CAD Multiple risk factors raise the risk for MI Lifetime risk of diabetes for individuals born in 2000 Diabetes as a CHD risk equivalent: Impact on mortality in women and men VBWG Over 1 million Americans will have an MI this year

Physiology of RAAS: Focus on Angiotensin

Download VBWG05CoreCAD-S2.ppt (23 slides - 0.6MB)

Physiology of RAAS:Focus on Angiotensin RAAS: Pathways of ACE inhibition and angiotensin receptor blockade Atherosclerosis-promoting actions of Ang II and protective effects of bradykinin Ang II: Influence on structure, function, and atherosclerosis ACEI: Proposed continuum of benefits Hypercholesterolemia increases angiotensin peptides and atherosclerosis via AT1A receptor Reduction in infarct size with ACE inhibition: Involvement of bradykinin ACEI reduces atherosclerosis progression ACEI may exert anti-ischemic effects in CAD ACEI is associated with less aortic valve calcification ACEI normalizes structure of resistance arteries in CAD patients Short term ACEI does not improve transient ischemia in CAD Adipocyte and vasculature interactions RAAS blockade increases adiponectin ACEI increases tPA release through endogenous bradykinin Sustained decrease in PAI-1 antigen over time with ACEI vs ARB Greater decrease in PAI-1 over time with ACEI vs ARB Differing effects of ACEI and ARB on tPA release Effects of ACEI on endothelial function: EUROPA substudies PERTINENT: Study design PERTINENT: Effects of treatment with perindopril for 1 year PERFECT: Study design PERFECT: ACEI and endothelial function—Preliminary results

Role of RAAS Modulation: Recent Clinical Trials

Download VBWG05CoreCAD-S3.ppt (44 slides - 1.2MB)

Role of RAAS Modulation:Recent Clinical TrialsBenefit of ACE inhibition in CAD EUROPA: EUropean trial on Reduction Of  cardiac events with Perindopril in stable coronary Artery disease EUROPA: Baseline characteristics EUROPA: Concomitant medications EUROPA: Primary outcome EUROPA: Effect of ACEI on fatal/nonfatal MI and HF hospitalizations EUROPA: Benefit of ACEI on primary and secondary outcomesEUROPA: Benefit of ACEI on selected secondary outcomes EUROPA: Consistent benefits in predefined subgroups EUROPA: Consistent benefits in predefined subgroups (continued) EUROPA: Benefit of perindopril was on top of recommended medications EUROPA: Risk reduction with perindopril stratified by baseline systolic BP level EUROPA: Systolic BP reduction during run-in did not affect risk reduction during trialEUROPA vs HOPE: Inclusion criteria EUROPA vs HOPE: Study populations EUROPA vs HOPE: Event rates in placebo groups reflect differences in baseline risk EUROPA vs HOPE: Treatment more intensive in EUROPA than in HOPE EUROPA: Clinical implications PEACE: Prevention of Events with Angiotensin Converting Enzyme inhibition PEACE: Primary outcome EUROPA vs PEACE: Differences in compliance ACEI trials in CAD without HF: Primary outcomes ACEI trials in CAD patients without HF: Key baseline characteristics EUROPA, HOPE, PEACE, QUIET: Totality of trial evidence EUROPA, HOPE, PEACE, QUIET: CV therapies at entry/during study ACEI outcome trials in CAD patients without HF: BP at entry/during study HOPE, EUROPA, PEACE, QUIET: Differences in baseline CV risk EUROPA, HOPE: Consistent benefit of ACEI on CV outcomes Should all patients with stable CAD without HF receive an ACEI? Interpreting evidence Evidence-based medicine: Updated guide-lines for ACEI in CAD patients without HF ACP guidelines for ACEI in chronic stable angina or asymptomatic CAD PERSUADE: PERindorpil SUbstudy of coronary Artery disease and DiabEtes: The diabetic substudy of EUROPA PERSUADE: Primary outcome PERSUADE and EUROPA: Comparable outcomes PERSUADE and MICRO-HOPE: Consistency of benefit PERSUADE: Clinical implications Are all ACEIs the same? Survival                                                1-year post-MI by ACEI at discharge Multiple mechanisms of ACEI in atherosclerotic CVD Clinical trials of ARBs: CV outcomes LIFE: Effects of ARB vs -blockade on primary outcome and components VALUE: Similar treatment effectson primary outcome at study end VALUE: SBP and outcome differencesduring consecutive time periods Evidence of benefit: ACEI vs ARB

VBWG

Download VBWG05CoreCAD-S4.ppt (8 slides - 0.4MB)

VBWG Disease progression in nonstented lesions causes most CV events Predictors of nontarget lesion PCI for progression of disease Improving long-term outcomes after PCI CRUSADE: Discharge care for CABG vs PCI CRUSADE: Hospital variations in quality of care vs outcome Greater use of evidence-based medications lowers 6-month mortality in ACS patients Potential long-term risk reduction with cardioprotective medications in post-MI patients

VBWG

Download VBWG05CoreCAD-S5.ppt (8 slides - 0.2MB)

VBWG Updated guidelines: Classes of Recommendations and levels of evidence ACC/AHA: Update for management of chronic stable angina—asymptomatic patients ACC/AHA guidelines: Discharge therapy after unstable angina/NSTEMI–Class I interventions ACC/AHA: Discharge medical therapy after STEMI–Class I interventions RALES and EPHESUS: Aldosterone blockade in HF and post-MI LV dysfunction Aldosterone blockade and AT1 receptor blockade: Trials in post-MI LV dysfunction and HF ESC Guidelines: ACEI in secondary prevention and to prevent sudden death
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, CV Therapeutics Inc, or the publisher.
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© 2005 Medical Education Consultants, LLCSM (MEDCON). All rights reserved.

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