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.

Review of an article

Benefits of ACE inhibition1

“The decrease in angiotensin II levels prevents a number of deleterious cardiovascular effects, while the increase of bradykinin has cardioprotective consequences.”

1. DiNicolantonio J, Lavie C, O’Keefe J. Not all angiotensin-converting enzyme inhibitors are equal: focus on ramipril and perindopril. PostgradMed. 2013;125:154-168.2. 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-angiotensin-

aldosterone system inhibitors involving 158 998 patients. Eur Heart J. 2012;33(16):2088-2097. 3. Strauss MH, Hall AS. Angiotensin receptor blockers may increase risk of myocardial infarction: unraveling the ARB-MI paradox.Circulation. 2006;114(8):838-854.

“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

Adhesion of monocytes

SMC growth, proliferation, and migration

Increased PAI-1 and thrombogenesis

Matrix degradation

Oxygen free radical production

Endothelial dysfunction

Vasodilation

Antiadhesion of monocytes

Increased eNOS expression

Increased t-PA and fibrinolysis

Antiremodeling effect

Antioxidant effect

Preserved endothelial function

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 equalA clinical view: ACE inhibitors in CHD patients

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

“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).”

Not all ACE inhibitors are equalPost 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 infarctionDiNicolantonio 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.