Extension studies show sustained benefits with ACEI TreatmentRamiprilEnalaprilEnalaprilRamipril Follow-up15 mos10 yrs12 yrs7.2 yrs Characteristic Clinical HF,NYHA class IVHF, LV High CV risk, post-MIHFdysfunctionno LV dysfunction no HF Results RRR 36%Overall survivalExtendedReduced major in mortalityprolonged survival CV events and by 50% by 9.4 monew diabetes by 34% SummaryContinue ACEIBeneficial effect Sustained Sustained indefinitely post-MImaintainedimprovementbenefit with several yrsin survivallong-term use AIREXCONSENSUSX-SOLVDHOPE-TOO Hall AS et al. Lancet. 1997;349: Swedberg K et al. Eur Heart J. 1999;20: Jong P et al. Lancet. 2003;361: HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112: Dosage important VBWG

HOPE-TOO: Study disposition Ramipril (n = 3393) Placebo (n = 3393) Follow-up ACEI therapy: >90% ramipril “Late” ACEI: Placebo patients from HOPE Open-label ACEI therapy (n = 2211) “Early” ACEI: Ramipril patients from HOPE Open-label ACEI therapy (n = 2317) Primary analysis 174 study centers (n = 6786) HOPE-TOO participants agreed to passive follow-up (n = 4528) Adapted from HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112: Inclusion criteria: Age ≥55 years Hx: CAD, stroke, PVD or diabetes + ≥1 CV risk factor Exclusion criteria: CHF, known EF <0.4, Uncontrolled HTN; MI or stroke ≤4 wks; current ACEI, vit E use VBWG

HOPE-TOO: Baseline characteristics in extended follow-up Characteristic Ramipril (%) (n = 3393) Placebo (%) (n = 3393) CAD MI Stroke PAD Hypertension Diabetes Elevated total-C Current cigarette smoking Medications  -Blockers Aspirin or other antiplatelet agents Lipid-lowering drugs Diuretics Calcium channel blockers LV hypertrophy on ECG Microalbuminuria VBWG HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112:

HOPE-TOO: Primary outcome (CV death, MI, stroke) HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112: RRR = 17% P = Placebo Ramipril Years Primary outcome (% HOPE-TOO patients) Placebo Ramipril n HOPE-TOO begins Main HOPE study ends VBWG

HOPE-TOO: Additional risk reduction in major CV events and new-onset diabetes VBWG HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112: % 34% 16% Revascularization New-onset diabetes MI % Reduction with ramipril

Benefit of treatment with ACEI Sustained, irreversible, favorable ventricular/vascular remodeling RAAS blockade provides sustainable, favorable effect on glucose homeostasis Benefits are additive to ancillary therapy and extend to all patients, independent of baseline risk “Earlier” rather than later initiation provides longer-term protection HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112: VBWG