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.