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• Advancing Our Understanding of RAAS Modulation in High-Risk Patients


VBWG_06_RAAS.pdf (1.3MB)VBWG_06_RAAS.pdf (1.3MB)

Advancing Our Understanding of RAAS Modulation in High-Risk Patients

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Advancing Our Understanding of RAAS Modulation in High-Risk Patients CVD has risen, accompanied by diabetes Continued increase in CVD and diabetes is predicted in US Discharge ACEI post-MI remains suboptimal AHA/ACC secondary-prevention guidelines: ACEIs and ARBs

Critical Role of RAAS in Vasculoprotection: New Science

Download VBWG_06_RAAS_Sec2.ppt (20 slides - 3.6MB)

Critical Role of RAAS in Vasculoprotection: New Science New aspects of RAAS RAAS: Current and potential targets Impact of ACEI on ACE signaling pathway ACE metabolism ACEI mechanism of benefit: Reduction in clinical events Renin inhibition prevents LVH in animal models Demonstrated benefits of AT1R blockade AT1R blockade upregulates both Ang II levels and AT2R expression Postulated role of AT2R and MMP-1 in plaque destabilization AT2R mediates cardiac myocyte enlargement during pressure overload Sustained decrease in PAI-1 antigen over time with ACEI vs ARB ACEIs and bradykinin oppose Ang II effects Ang II effect in target organ damage Potential role of RAAS activation in metabolic syndrome and diabetes RAAS activation in obesity RAAS activation contributes to obesity-related hypertension ACEIs: Potential mechanisms of improved glucose metabolism Role of Ang II in insulin resistance: Focus on signaling pathways ACEIs improve glucose uptake in peripheral tissue

RAAS Modulation in High-Risk Patients

Download VBWG_06_RAAS_Sec3.ppt (42 slides - 1.2MB)

RAAS Modulationin High-Risk Patients ACEIs: Evolution of benefits Effect of ACEIs and ARBs on new-onset diabetes HOPE, EUROPA, PEACE: Reduction in new-onset diabetes (placebo-controlled trials) TZDs blunt diabetes progression DPP: Long-term benefit of lifestyle intervention or metformin on diabetes prevention DREAM: Background DREAM: Study design DREAM: 2 × 2 factorial design DREAM: Adjudicated HF DREAM: Ramipril effect on new-onset diabetes or death DREAM: Ramipril effect on glycemia DREAM: Rosiglitazone effect on primary end point DREAM: Conversion to normoglycemia with rosiglitazone DREAM: Safety DREAM: Clinical implications Evolution of ACE inhibition for treating patients with CHD Meta-analyses show consistency of ACEI benefit in preventing CV events EUROPA, HOPE, PEACE, QUIET: Treatment effect on CV end points HOPE, EUROPA, PEACE: Overview HOPE, EUROPA, PEACE: Reduction in all-cause mortality HOPE, EUROPA: Benefit consistent across ancillary therapy HOPE, EUROPA: Benefit of ACEIs consistent across baseline combinations Benefit of ACEIs in patients with/withoutLVD or HF EUROPA: Consistent risk reduction regardless of baseline risk HOPE, EUROPA, PEACE: Benefit of ACEIs across broad spectrum of risk ACEIs in vascular disease: Conclusions ACEIs and elevated serum creatinine in renal insufficiency HOPE: CV end point by baseline creatinine Meta-analysis of trials comparing ARB vs placebo, non-ACEI comparators, or ACEI Meta-analyses of ACEI and ARB trials ACEIs vs ARBs: Comparative effect on stroke, HF, and CHD EPHESUS: New subgroup analysis Role of RAAS modulation continues to evolve ONTARGET: Study design TRANSCEND: Study design ONTARGET/TRANSCEND: Baseline medical conditions vs HOPE ONTARGET/TRANSCEND: Baseline medications vs HOPE NAVIGATOR: Study design EMPHASIZE-HF: Study design TOPCAT: Study design RAAS modulation in high-risk patients: Summary
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