Surrogate End Points in Clinical Trials of ACE Inhibition Are We Being Misled

Surrogate End Points in Clinical Trials of ACE Inhibition Are We Being Misled  

In the field of hypertension, despite the unfortunate and unexpected adverse effects of practolol, tienilic acid, and mibefradil, it has been generally considered that fall in blood pressure was an acceptable sur- 

In the same way, one can also look at the results of ACE inhibition in renal insufficiency. The decrease in the rate of deterioration of renal function verifies experimental concepts and is reassuring for the prevention of long-term renal function deterioration in hypertensive patients. In untreated hypertensive patients, cerebrovascular and cardiac events occured quite frequently before renal insufficiency, which 

For the last 20 years, the translation of scientific data into practice recommendations has been moving between these two extreme concepts of medicine. Therefore, too many patients are exposed to the most expensive drug instead of this therapeutic approach being specifically targeted toward those who will benefit from it, for instance, those who have microalbuminuria (399). 

If we are quite certain that ACE immobilized at the surface of the endotheliaf celfs is physiologicaliy more important than is the circulating enzyme (197), we do not know yet what is the relative importance of its bland C-terminal active sites. We do not know how they possibly affect the activity of each other. We do not know the physiological role of the N-acetyl SDKP, a relatively specific substrate of the N-terminal active site. We may still discover other natural substrates for endothelial and epithelial ACE. We do not fully understand the basis of differences in the various daily doses of ACE inhibitors as usually prescribed, from trandolapril 2 mg/day to lisinopril 80 mg/day, and the consequences of dose choices. 

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