Randomised trial of ramipril in repaired tetralogy of Fallot and pulmonary regurgitation: the APPROPRIATE study (Ace inhibitors for Potential PRevention Of the deleterious effects of Pulmonary Regurgitation In Adults with repaired TEtralogy of Fallot)

Int J Cardiol. 2012 Feb 9;154(3):299-305. doi: 10.1016/j.ijcard.2010.09.057. Epub 2010 Oct 22.


Background: Optimal treatment for stable repaired tetralogy of Fallot (rTOF) patients with pulmonary regurgitation (PR) and related right ventricular (RV) dilatation, including timing of valve implantation, remains uncertain. We sought to study tolerability of the angiotensin-converting-enzyme (ACE) inhibitor ramipril and its effects on cardiovascular function in these patients.

Methods: Clinically stable rTOF patients with moderate/severe PR were included. A double-blinded, placebo-controlled study of 6 months of ramipril vs placebo was performed. All patients underwent cardiovascular magnetic resonance (CMR), echocardiography, neurohormonal analysis, and objective cardiopulmonary exercise testing at baseline and follow-up.

Primary endpoint: The main aim was to detect changes in RV function (primary endpoint CMR-derived RV ejection fraction).

Results: Seventy-two patients were enrolled and 64 qualified for the final analysis. There was no difference in the primary endpoint RV ejection fraction. RV long-axis shortening significantly improved in the ramipril group compared to placebo (RV: 2.3 ± 3.8 vs 0.02 ± 2.7 mm; P=0.017) as did LV long-axis shortening (1.9 ± 4.5 vs -0.2 ± 3.7 mm respectively; P=0.030). No clear differences were detected between ramipril and placebo for other measures. In a subgroup of patients with restrictive RV physiology, ramipril resulted in decrease in LV end-systolic volume index and increase in LVEF (-2.4 ± 5.0 vs 2.7 ± 3.6 mL/m(2); P=0.005, 2.5 ± 5.0 vs -1.3 ± 3.5%; P=0.03). Ramipril did not cause adverse events and was well tolerated.

Conclusions: Ramipril is a well tolerated therapy, improves biventricular function in patients with rTOF and may have a particular role in patients with restrictive RV physiology. Larger, longer-term studies are needed to determine if ACE inhibitors can improve both ventricular remodelling and clinical outcomes. (

Isrctn: 97515585).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Double-Blind Method
  • Feasibility Studies
  • Humans
  • Prospective Studies
  • Pulmonary Valve Insufficiency / complications*
  • Pulmonary Valve Insufficiency / physiopathology
  • Ramipril / therapeutic use*
  • Tetralogy of Fallot / complications*
  • Tetralogy of Fallot / physiopathology
  • Tetralogy of Fallot / surgery
  • Time Factors
  • Ventricular Function / drug effects*


  • Angiotensin-Converting Enzyme Inhibitors
  • Ramipril

Associated data

  • ISRCTN/ISRCTN97515585