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.

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