METABOLIC EFFECTS OF LONG-TERM ANGIOTENSIN-CONVERTING ENZYME-INHIBITION WITH FOSINOPRIL IN PATIENTS WITH ESSENTIAL-HYPERTENSION - RELATIONSHIP TO ANGIOTENSIN-CONVERTING ENZYME-INHIBITION

Fifty patients with mild to moderate essential hypertension were rando mized to receive either 20 mg fosinopril daily for 16 weeks or placebo for 4 weeks followed by 12 weeks of 50 mg atenolol daily. Prior to th ese 16 weeks there was a placebo wash-out period of 2-6 weeks. Blood p ressure measurements, euglycaemic, hyperinsulinaemic glucose clamps, a nd intravenous glucose tolerance tests (IVGTT) were performed at basel ine and after 4 and 16 weeks. Blood lipid status was evaluated at base line and 16 weeks. The insulin sensitivity index (M/I) increased by 12 % during the prolonged placebo period, and subsequently decreased by 1 2% during treatment with atenolol in that group. A post-hoc analysis o f covariance indicated that the increase in insulin sensitivity during the initial 4 weeks may have been due to carry-over effects from prev ious antihypertensive treatment. Fosinopril increased glucose disappea rance during IVGTT at 4 and 16 weeks (k values 1.46 and 1.33 vs 1.10 a t baseline) but had no effect on insulin sensitivity. The change in in sulin sensitivity and serum triglycerides during treatment with fosino pril was related to angiotensin-converting enzyme inhibition in serum. In conclusion, carry-over effects from previous antihypertensive medi cation were indicated in this study, probably because of an insufficie nt wash-out period in many patients. Therefore, 4 weeks of placebo was h-out in all patients is advisable in this kind of investigation.