CHOOSING THE RIGHT ACE-INHIBITOR - A GUIDE TO SELECTION

To find out if there are one or more criteria to guide selection among the ACE inhibitors for the treatment of arterial hypertension, we hav e reviewed the principal pharmacokinetic and pharmacodynamic aspects o f the more frequently used agents of this class of antihypertensive dr ugs. Among the pharmacokinetic aspects that we have considered, termin al half-life, as related to the duration of the antihypertensive effec t, and the route of elimination may have an impact in the clinical sel ection among the various ACE inhibitors. On the other hand, all the ot her characteristics have no pragmatic clinical relevance or may be cor rected by dosage adjustment. Among the pharmacodynamic aspects, the an tihypertensive efficacy of the different ACE inhibitors seems to be ve ry similar, and some of the differences found in different studies are probably due to the population investigated and to the protocol of th e study (time of blood pressure measurements, diet, drug dosage etc.). However, some differences can be found among the various ACE inhibito rs when the antihypertensive efficacy is evaluated also as trough to p eak ratio of blood pressure reduction. Indeed, in respect of the admin istration schedule of each ACE inhibitor not all the agents of this cl ass have a trough to peak ratio above 50 to 60%, as suggested by the F ood and Drug Administration of the US. According to this criterion, es pecially when blood pressure is measured with 24-hour noninvasive ambu latory blood pressure monitoring, some drugs such as lisinopril, enala pril and trandolapril should be preferred for their higher trough to p eak ratios. Left ventricular hypertrophy is significantly reduced by a ntihypertensive agents, the ACE inhibitors being the most effective. I ndeed, the reduction of left ventricle mass for each 1mm Hg reduction in mean blood pressure is greater for ACE inhibitors than for other cl asses of antihypertensive agents. However, this effect seems more clas s related than characteristic of one or more among the various ACE inh ibitors. Insulin resistance is elevated in hypertensive patients and i t has been thought responsible for or associated with other metabolic abnormalities. ACE inhibitors seem to correct the insulin resistance o f hypertensive patients, but this effect also appears to be class rela ted more than limited to one ACE inhibitor or another. Our knowledge o f this field is still Limited and more studies are necessary, especial ly to understand the prognostic impact of insulin resistance and/or in sulin resistance improvement. Renal protection of ACE inhibitors was f irst evaluated in patients with scleroderma crises, and thereafter has been extensively investigated in patients with renal insufficiency, d ue 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 inhibito rs in patients with renal insufficiency due to nondiabetic nephropathy . In hypertensive patients with normal renal function and microprotein uria the ACE inhibitors reduce blood pressure and microalbuminuria in shea and long term studies, without lowering glomerular filtration rat e and renal blood flow. Renoprotection has been investigated predomina ntly with captopril and enalapril and they seem equipotent. No clinica lly relevant significant differences have been found among the ACE inh ibitors in their use in elderly hypertensive patients and in their imp act on quality of life. Finally, the effect of ACE inhibitors on ather osclerotic disease of carotid arteries is the subject of ongoing studi es. In conclusion, there is no clinically relevant difference among th e various ACE inhibitors for the treatment of patients with uncomplica ted essential hypertension, when the agents are administered in the co rrect dosage regimen. However, if we consider the trough to peak ratio of blood pressure reduction, some of them seem to have a more favoura ble profile, although the long term impact is still unknown. Hypertens ive patients with renal insufficiency, secondary either to hypertensio n or to other disease, seem to benefit from ail ACE inhibitors, but so me of them with a double route of excretion could be selected in compa rison with those eliminated renally only because they do not need dosa ge adjustment.