Angiotensin antagonism in coronary artery disease: results after coronary revascularisation

The renin-angiotensin system (RAS) is an ancient and complex cascade of homeostatic reactions aimed at regulating primordial functions that ensure organ perfusion through the control of blood pressure and the regulation of renal-cardiac activity. However, the over-expression or lack of compensatory mechanisms of any of its components may initiate detrimental effects that potentially lead to disease, a balance that makes the RAS a sequence with a labile physiological equilibrium and with a strong harm potential. These characteristics of the RAS in general, and of the angiotensin converting enzyme (ACE) in particular, make it not only an important complex for the regulation of blood pressure and neuropeptide metabolism, but also a fascinating subject of study from a biochemical, evolutionary and genetic point of view. Pharmacological interventions that influence the RAS by inhibiting the ACE or the angiotensin II type 1 receptor (AT1R) have demonstrated sustained efficacy in reducing the incidence of cardiovascular events and, consequently, vascular mortality in several clinical situations. ACE inhibitors and angiotensin II receptor antagonists (ARAs) reduce blood pressure and have cardio- and vasculoprotective effects. Anti-atherosclerotic effects have also been attributed to these drugs. For these reasons, it has been hypothesised that RAS inhibitors could also reduce the recurrence of ischaemic events after myocardial revascularisation procedures, namely coronary artery by-pass graft surgery (CABG) or percutaneous coronary interventions (PCI). Information available on the effect of ACE inhibitors and ARAs in patients with coronary artery disease (CAD) previously treated with revascularisation techniques indicates a substantial reduction of mortality and infarction in these patients. However, data regarding the progression of CAD, restenosis or reocclusion of vascular conduits of the coronary circulation after myocardial revascularisation are inconsistent. In most studies, the administration of ACE inhibitors neither improved the ischaemic threshold nor reduced the need for new revascularisation procedures. On the contrary, ACE inhibitors have been associated with higher restenosis rates after PCI in some retrospective series. Conversely, a single, exploratory randomised trial demonstrated that the selective AT1R antagonist valsartan significantly reduced stent restenosis after PCI. In patients undergoing CABG, ACE inhibitors did not reduce the risk of graft degeneration or occlusion. Studies that evaluated a possible anti-atherosclerotic effect of ACE inhibitors (including some large randomised trials) have generally been negative.