Why is perindopril the ACE inhibitor of choice for EUROPA?
Coronary artery disease has been shown to be clearly associated with
abnormalities of the renin-angiotensin aldosterone system (RAAS). Consequently,
perindopril, a long-acting ACE inhibitor that inhibits the formation of angiotensin
II and increases bradykinin levels, is an extremely promising weapon in the
fight against coronary artery disease.
Perindopril is indicated for the treatment of hypertension and heart failure.
Many clinical trials have demonstrated its efficacy in cardiovascular
disease, including the treatment of hypertension, heart failure and post
myocardial infarction (MI). Its antihypertensive efficacy with a 4 mg
and 8 mg dose once daily dose has been proven over a 24-hour period and
it is well tolerated even in high-risk patients, such as the elderly or
in patients with heart failure or recent ischaemic stroke, in whom it
causes no changes in cerebral circulation.
The beneficial effects of perindopril on cardiovascular remodelling are
well documented. These benefits include improvement of arterial compliance
in large arteries; restoration of the structure of small resistance arteries;
restoration of flow-mediated coronary vasodilatation in hypertensive patients
and the reversal of endothelial dysfunction in patients with hypertension
and heart failure.
Furthermore, Perindopril has a very high tissue and plasma affinity, as
proven for the first time ever with an ACEI in humans
suffering from CAD in this study. As shown in the
picture below, Perindopril inhibits both endothelial
and advential ACE, this being further proof supporting
its choice for the EUROPA trial.
Perindopril has also been shown to cause a notable reduction in myocardial
ischaemia. Its anti-atherosclerotic properties have been demonstrated
in an experimental model of atherosclerosis, in which perindopril significantly
reduced atherosclerotic lesion size and made them more stable and less
likely to rupture. In addition, perindopril decreased the number of lipid-laden
macrophages and reduced lipid accumulation in developing atherosclerotic
plaques, or even prevents the development of atherosclerotic lesions.
Furthermore, a recent large-scale study using perindopril illustrated the
potential for perindopril in patients with stable coronary artery disease.
The Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS Collaborative
Group, 2001) demonstrated that a drug regimen based on perindopril significantly
reduced the risk of stroke by 28%, the risk of MI by 38% and heart failure
by 26%. These benefits were noticed even in patients without hypertension
suggesting that perindopril may have benefits above and beyond its role
as a blood-pressure lowering agent.