To find out if there are one or more criteria to guide selection among the ACE inhibitors for the treatment of arterial hypertension, we have reviewed the principal pharmacokinetic and pharmacodynamic aspects of the more frequently used agents of this class of antihypertensive drugs. Among the pharmacokinetic aspects that we have considered, terminal half-life, as related to the duration of the antihypertensive effect, and the route of elimination may have an impact in the clinical selection among the various ACE inhibitors. On the other hand, all the other characteristics have no pragmatic clinical relevance or may be corrected by dosage adjustment. Among the pharmacodynamic aspects, the antihypertensive efficacy of the different ACE inhibitors seems to be very similar, and some of the differences found in different studies are probably due to the population investigated and to the protocol of the study (time of blood pressure measurements, diet, drug dosage etc.). However, some differences can be found among the various ACE inhibitors when the antihypertensive efficacy is evaluated also as trough to peak ratio of blood pressure reduction. Indeed, in respect of the administration schedule of each ACE inhibitor not all the agents of this class have a trough to peak ratio above 50 to 60%, as suggested by the Food and Drug Administration of the US. According to this criterion, especially when blood pressure is measured with 24-hour noninvasive ambulatory blood pressure monitoring, some drugs such as lisinopril, enalapril and trandolapril should be preferred for their higher trough to peak ratios. Left ventricular hypertrophy is significantly reduced by antihypertensive agents, the ACE inhibitors being the most effective. Indeed, the reduction of left ventricle mass for each 1mm Hg reduction in mean blood pressure is greater for ACE inhibitors than for other classes of antihypertensive agents. However, this effect seems more class related than characteristic of one or more among the various ACE inhibitors. Insulin resistance is elevated in hypertensive patients and it has been thought responsible for or associated with other metabolic abnormalities. ACE inhibitors seem to correct the insulin resistance of hypertensive patients, but this effect also appears to be class related more than limited to one ACE inhibitor or another. Our knowledge of this field is still Limited and more studies are necessary, especially to understand the prognostic impact of insulin resistance and/or insulin resistance improvement. Renal protection of ACE inhibitors was first evaluated in patients with scleroderma crises, and thereafter has been extensively investigated in patients with renal insufficiency, due to diabetic nephropathy, with or without arterial hypertension. In both clinical diseases ACE inhibitors caused a significant improvement in prognosis. More doubtful are the long term effects of ACE inhibitors in patients with renal insufficiency due to nondiabetic nephropathy. In hypertensive patients with normal renal function and microproteinuria the ACE inhibitors reduce blood pressure and microalbuminuria in shea and long term studies, without lowering glomerular filtration rate and renal blood flow. Renoprotection has been investigated predominantly with captopril and enalapril and they seem equipotent. No clinically relevant significant differences have been found among the ACE inhibitors in their use in elderly hypertensive patients and in their impact on quality of life. Finally, the effect of ACE inhibitors on atherosclerotic disease of carotid arteries is the subject of ongoing studies. In conclusion, there is no clinically relevant difference among the various ACE inhibitors for the treatment of patients with uncomplicated essential hypertension, when the agents are administered in the correct dosage regimen. However, if we consider the trough to peak ratio of blood pressure reduction, some of them seem to have a more favourable profile, although the long term impact is still unknown. Hypertensive patients with renal insufficiency, secondary either to hypertension or to other disease, seem to benefit from ail ACE inhibitors, but some of them with a double route of excretion could be selected in comparison with those eliminated renally only because they do not need dosage adjustment.
