Review of an article
Not all Angiotension-Converting Enzyme
(ACE) inhibitors are Equal: Focus on
Ramipril and Perindopril
DiNicolantonio J, Lavie C, O’Keefe J. Not all angiotensin-converting enzyme inhibitors are equal: focus on ramipril and perindopril. Postgrad Med. 2013;125:154-168.
Benefits of ACE inhibition1
“ACE inhibitors are effective agents for treating patients with hypertension, and current data
suggest that they are more effective therapeutic agents for reducing rates of morbidity and
mortality due to cardiovascular (CV) events compared with the use of angiotensin receptor
blockers.” 2,3
ACE inhibition
 Angiotensin II
 Bradykinin
 Vasoconstriction
 Vasodilation
 Adhesion of monocytes
 Antiadhesion of monocytes
 SMC growth, proliferation, and migration
 Increased eNOS expression
 Increased PAI-1 and thrombogenesis
 Increased t-PA and fibrinolysis
 Matrix degradation
 Antiremodeling effect
 Oxygen free radical production
 Antioxidant effect
 Endothelial dysfunction
 Preserved endothelial function
“The decrease in angiotensin II levels prevents a number of deleterious cardiovascular effects,
while the increase of bradykinin has cardioprotective consequences.”
1.
2.
3.
DiNicolantonio J, Lavie C, O’Keefe J. Not all angiotensin-converting enzyme inhibitors are equal: focus on ramipril and perindopril. PostgradMed. 2013;125:154-168.
van Vark LC, Bertrand M, Akkerhuis KM, et al. Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensinaldosterone system inhibitors involving 158 998 patients. Eur Heart J. 2012;33(16):2088-2097.
Strauss MH, Hall AS. Angiotensin receptor blockers may increase risk of myocardial infarction: unraveling the ARB-MI paradox.Circulation. 2006;114(8):838-854.
Not all ACE inhibitors are equal
A pharmacokinetic/pharmacodynamic view
Among ACE inhibitors, perindopril causes a greater increase in bradykinin
DiNicolantonio J, Lavie C, O’Keefe J. Not all angiotensinconverting enzyme inhibitors are equal: focus on ramipril and perindopril. Postgraduate Medicine. 2013;125:154-168
Not all ACE inhibitors are equal
A clinical view: ACE inhibitors in CHD patients
“Only use of the ACE inhibitor perindopril
has demonstrated clear reductions in CV
end points in patients who have been
treated in ways that are reflective of
current-day intensive practice
(ie, on optimal medical therapy and at a
lower baseline risk of CV events compared
with patients receiving ramipril in HOPE).”
Abbreviations: ACE, angiotensin-converting enzyme; CHD, coronary heart disease;
CAMELOT, Coparison of AMlodipine versus Enalapril to Limit Occurrences of
Thrombosis; EUROPEAN, European Trial on Reduction of Cardiac Events With
Perindopril in Stable Coronary Artery Disease; HOPE, Heart Outcomes Prevention
Evaluation; PEACE, Prevention of Events with Angiotensin Converting Enzyme inhibition;
QUIET, QUinapril Ischemic Event Trial.
DiNicolantonio J, Lavie C, O’Keefe J. Not all angiotensin-converting enzyme inhibitors
are equal: focus on ramipril and perindopril. Postgrad Med. 2013;125:154-168
Not all ACE inhibitors are equal
Post MI patients treated by perindopril: the PREAMY study
Design: 12 month, double-blinded randomized clinical trial.
Aim: To compare the benefits of Coversyl vs placebo in elderly patients with acute
myocardial infarction.
Primary end point (patient mortality, hospitalization for heart failure, or left
ventricular remodeling) was significantly reduced by 22% with Coversyl (P>0.001).
Conclusion
“In summary, perindopril therapy was shown to be beneficial in patients with a recent
AMI, despite patients having a normal EF.”
Abbreviation: AMI, acute myocardial infarction
DiNicolantonio J, Lavie C, O’Keefe J. Not all angiotensin-converting enzyme inhibitors are equal: focus on ramipril and perindopril. Postgrad Med. 2013;125:154-168.
Conclusion
“Perindopril has been shown to have a longer duration of action, higher
lipophilicity, and stronger tissue ACE-inhibiting properties compared with
other ACE inhibitors. Moreover, there are several clinical trials supporting the
CV benefit of perindopril therapy in many clinical settings (eg, patients with
AMI, those with HF and preserved EF, patients with or at high risk for CHD
without HF).
Thus, perindopril should be strongly considered as a first-choice ACE
inhibitor for treatment of patients with HF and preserved EF and in patients
with or at high risk for CHD without HF.”
DiNicolantonio J, Lavie C, O’Keefe J. Not all angiotensin-converting enzyme inhibitors are equal: focus on ramipril and perindopril. Postgrad Med. 2013;125:154-168.