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VBWG. Extension studies show sustained benefits with ACEI. AIREX CONSENSUS X-SOLVD HOPE-TOO. 1997 1999 2003 2005. Treatment Ramipril Enalapril Enalapril Ramipril Follow-up 15 mos 10 yrs 12 yrs 7.2 yrs
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VBWG Extension studies show sustained benefits with ACEI AIREX CONSENSUS X-SOLVD HOPE-TOO 1997 1999 2003 2005 Treatment Ramipril Enalapril Enalapril Ramipril Follow-up 15 mos 10 yrs 12 yrs 7.2 yrs Characteristic Clinical HF, NYHA class IV HF, LV High CV risk, post-MI HF dysfunction no LV dysfunction no HF ResultsRRR 36% Overall survival Extended Reduced major in mortality prolonged survival CV events and by 50% by 9.4 mo new diabetes by 34% SummaryContinue ACEI Beneficial effect Sustained Sustained indefinitely post-MI maintained improvement benefit with several yrs in survival long-term use Dosageimportant Hall AS et al. Lancet. 1997;349:1493-7. Swedberg K et al. Eur Heart J. 1999;20:136-9. Jong P et al. Lancet. 2003;361:1843-8.HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112:1339-46.
VBWG HOPE-TOO: Study disposition Inclusion criteria:Age ≥55 years Hx: CAD, stroke, PVD ordiabetes + ≥1 CV risk factor Exclusion criteria:CHF, known EF <0.4, Uncontrolled HTN; MI or stroke ≤4 wks; current ACEI, vit E use 174 study centers(n = 6786) Primary analysis Placebo (n = 3393) Ramipril(n = 3393) HOPE-TOO participantsagreed to passive follow-up(n = 4528) “Early” ACEI: Ramipril patientsfrom HOPE “Late” ACEI: Placebo patients from HOPE Open-labelACEI therapy(n = 2317) Open-labelACEI therapy(n = 2211) Follow-up ACEI therapy:>90% ramipril Adapted from HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112:1339-46.
VBWG HOPE-TOO: Baseline characteristics in extended follow-up Ramipril (%)(n = 3393) Placebo (%)(n = 3393) Characteristic CAD 79.5 81.2 MI 52.3 53.5 Stroke 11.1 11.3 PAD 40.4 43.2 Hypertension 47.1 45.0 Diabetes 38.5 38.2 Elevated total-C 64.8 66.2 Current cigarette smoking 13.4 14.2 Medications-Blockers 39.8 40.1 Aspirin or other antiplatelet agents 74.8 77.0 Lipid-lowering drugs 28.5 29.3 Diuretics 15.6 15.2 Calcium channel blockers 46.1 47.3 LV hypertrophy on ECG 7.7 8.3 Microalbuminuria 19.3 20.3 HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112:1339-46.
HOPE-TOO begins Main HOPE study ends n PlaceboRamipril VBWG HOPE-TOO: Primary outcome (CV death, MI, stroke) 30 25 20 Primary outcome(% HOPE-TOO patients) 15 Placebo 10 RRR = 17% P = 0.0002 Ramipril 5 0 Years 4 5 6 0 1 2 3 7 46524645 44324456 15501731 42044256 39814079 36473789 27192819 19232075 HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112:1339-46.
VBWG HOPE-TOO: Additional risk reduction in major CV events and new-onset diabetes New-onset diabetes Revascularization MI 0 5 10 %Reductionwith ramipril 15 16% 20 19% 25 30 35 34% HOPE/HOPE-TOO Study Investigators. Circulation. 2005;112:1339-41.
VBWG 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;112:1339-46.