Prevention of Events with Angiotensin Converting Enzyme Inhibiton Trial (2004)

Design:  Double-blinded, Placebo-controlled RCT

Objective: When added to “modern conventional therapy”, does ACEI reduce the rate of nonfatal MI, CV death or revascularization in low risk patients with stable CAD and normal or slightly reduced LV function?

  • HOPE and EUROPA – CAD, vascular dx or diabtests and another CV risk factor – reduced rates of CV death or AMI with ACEI (Ramipril + Perindopril)
    • both trials enrolled patients without a history of HF
 P  N = 8290
> 50 yo, stable CAD, LVEF >40%, toleration of medication and successful completion of the run-in phase with >80% compliance with medication (trandolapril 2mg daily)

  • ~55% patients had documented MI

Excluded: valvular heart dx requriing surgical intervention, CABG or hospitalization for USA within preceding 3 mos (CABG) + 2 mos (USA), female + not using contraception
Median follow up of 4.8 years

 I Trandolapril 4mg daily
 C Placebo
 O  Primary end point: death from CV causes, MI or coronary revasularization

  • Primary endpoint: T: 21.9% vs. P: 22.5% (HR: 0.88-1.06, P = 0.43)
    • Sub-group analysis: NSS
  • BP dropped 4.4 + 0.3/3.6 + 0.2 in trandolapril group after 36 mos (SS difference vs. placebo)
  • NSS for efficacy endpoints – except:
    CHF as primary cause of hospitalization (HR: 0.75 (0.59-0.95), P = 0.02
    Onset of diabetes (HR: 0.83 (0.72-0.96), P = 0.01


  • SEs leading to D/C: T: 14.4%, P: 6.5% (P<0.001)
    • Most commonly cough and syncope

Take-away points:

  • SAVE (1992 – captopril), SOLVD (1991 – enalapril): ACEI decreased mortality and rate of development or worsening of symptomatic HF and asymptomatic LV dysfunction + decreased rate of subsequent MI
  • HOPE (2000-ramipril): high risk patients with vascular disease (incl. CAD) or diabetes with NO HF or low EF – ramipril reduced CV death, nonfatal MI, or stroke
  • EUROPA (2003- perindopril): Stable CAD without HF (lower risk than HOPE patients) – perindopril showed reduction in CV death, nonfatal MI, or cardiac arrest
  • PEACE trial patients: more intensive management of risk factors (greater % of patients on lipid lowering therapy and coronary re-vascularized)
  • ?benefit of ACEIs in all patients for CV benefit in “newer era” of MI management
    • Trandolapril – no benefit in “low risk patients” and normal EF who are on optimal therapy for MI management
  • Trandolapril in HF: TRACE (1995): post-MI HF – Trandolapril 4mg daily reduced the risk of CV death, sudden death and progression to severe HF, but no difference in recurrent MI
  • Consider cost – perindopril up to $1.26 per tablet vs. ramipril up to $0.20 per capsule