Factors determining the response to angiotensin-converting enzyme inhibitors in hypertension

Converting enzyme inhibitors, alone or in combination, are a safe and effective treatment for many hypertensives. However, the range of responses varies between individual patients and it has been claimed that there are two or three phases to the response. Pretreatment plasma renin (as an indication of activation of the renin angiotensin system) and the patient's age have been claimed to predict blood pressure fall. We have investigated whether these factors are useful indications of clinical response in mild-moderate essential hypertension. We have also investigated how well the response to the first dose correlates with the response to long-term (6 weeks) treatment. In a placebo-controlled trial of enalapril (20 mg daily), the blood pressure fall was analysed using an integrated pharmacokinetic/dynamic model of the concentration-effect relationship. The relation between the active drug concentration and blood pressure fall was best described by a non-linear Langmuir (Emax) model: E = (Emax C/C50 + C), where E is the effect, C the drug concentration, Emax is the maximum blood pressure fall and C50 is the drug concentration which causes a fall in blood pressure of 50% of the maximum. For a group of 13 essential hypertensives Emax was 46/20 mm Hg and C50 77 +/- 17 ng/ml. Emax was not related to age or pretreatment renin, but was positively correlated with pretreatment blood pressure (r = 0.69; p less than 0.01). Emax after 6 weeks of treatment (48 +/- 22 and 50 +/- 20 mm Hg, respectively, r = 0.89; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)