T he cardiovascular continuum is a sequence of related pathological predispositions and events running inexorably (if untreated) from risk factors to end-stage heart disease. Although its intimate mechanism is unknown and presumably multifactorial, key starting points include endothelial dysfunction and atherosclerosis, making inhibition of the renin-angiotensinaldosterone system (RAAS) the prime treatment target. As a class, angiotensinconverting enzyme (ACE) inhibitors have an established preventive and therapeutic role across the continuum, enjoying the highest levels of evidence for efficacy and tolerability. But ACE-inhibitor profiles differ in critical pharmacological and clinical respects. Perindopril and ramipril markedly reduce cardiovascular risk in stable coronary artery disease (CAD), unlike quinapril or trandolapril. Major differences exist in tissue ACE affinity, bradykinin selectivity and potentiation, and effects on endothelial apoptosis. Perindopril (active form: perindoprilat) has a relative tissue affinity much greater than that of other ACE inhibitors, correlating with its antiatherosclerotic activity. Its effect on bradykinin potentiation is particularly marked: the bradykinin/angiotensin I selectivity ratio is much greater in vitro than with other ACE inhibitors, accounting for its greater efficacy in reducing cardiovascular events. In vivo, perindopril increases endothelial nitric oxide synthase expression and activity more than trandolapril, quinapril, ramipril, and enalapril at equihypotensive doses. Perindopril, and to a lesser degree ramipril, are the only ACE inhibitors to significantly reduce apoptotic rate. The burden of the experimental and clinical evidence supports that an ACE inhibitor such as perindopril or ramipril is a superior therapeutic option, in particular in low-dose combination therapies, than certain other ACE inhibitors in stable CAD.

Do ACE inhibitors differ, and in which way?

FERRARI, Roberto
2009

Abstract

T he cardiovascular continuum is a sequence of related pathological predispositions and events running inexorably (if untreated) from risk factors to end-stage heart disease. Although its intimate mechanism is unknown and presumably multifactorial, key starting points include endothelial dysfunction and atherosclerosis, making inhibition of the renin-angiotensinaldosterone system (RAAS) the prime treatment target. As a class, angiotensinconverting enzyme (ACE) inhibitors have an established preventive and therapeutic role across the continuum, enjoying the highest levels of evidence for efficacy and tolerability. But ACE-inhibitor profiles differ in critical pharmacological and clinical respects. Perindopril and ramipril markedly reduce cardiovascular risk in stable coronary artery disease (CAD), unlike quinapril or trandolapril. Major differences exist in tissue ACE affinity, bradykinin selectivity and potentiation, and effects on endothelial apoptosis. Perindopril (active form: perindoprilat) has a relative tissue affinity much greater than that of other ACE inhibitors, correlating with its antiatherosclerotic activity. Its effect on bradykinin potentiation is particularly marked: the bradykinin/angiotensin I selectivity ratio is much greater in vitro than with other ACE inhibitors, accounting for its greater efficacy in reducing cardiovascular events. In vivo, perindopril increases endothelial nitric oxide synthase expression and activity more than trandolapril, quinapril, ramipril, and enalapril at equihypotensive doses. Perindopril, and to a lesser degree ramipril, are the only ACE inhibitors to significantly reduce apoptotic rate. The burden of the experimental and clinical evidence supports that an ACE inhibitor such as perindopril or ramipril is a superior therapeutic option, in particular in low-dose combination therapies, than certain other ACE inhibitors in stable CAD.
2009
Ferrari, Roberto
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1378318
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