Influence of Age on Blood Pressure Response to Enalapril

Abstract

Based on prevailing hypotheses about the role of renin in essential hypertension, both Laragh and Buhler independently predicted that angiotensin-converting enzyme (ACE) inhibitors would become less effective with increasing age, as elderly hypertensive patients tend to have low plasma renin activity. We have investigated this situation in a large postmarketing surveillance study with enalapril. Following a 2-week no-treatment period, a total of 11,710 patients with essential hypertension received 10–20 mg of enalapril once daily for 6 weeks. BP was measured on two occasions prior to enalapril treatment, and on two occasions during enalapril treatment (after 2 and 6 weeks). Enquiry for symptom events was also made on each of these four occasions. Systolic BP (SBP) prior to enalapril treatment rose steeply with increasing age, whereas diastolic BP (DBP) rose only very slightly with age and reached a plateau by the 5th decade. The fall in SBP in response to enalapril increased with increasing age, but DBP was relatively uninfluenced by age. However, when corrected for initial BP, the percentage changes in both SBP (13%) and DBP (14%) were not different across the age range studied. Prior to receiving enalapril, 67.8% of patients were reporting symptoms, and this showed a positive correlation with age. During enalapril therapy, the overall level of symptom events reported fell significantly in all age groups (35.0%) but more so in the elderly, such that at the end of the study no significant age-related difference was detected. In all age groups, more than half of the events reported during enalapril therapy were of an improvement in general well-being. This study further supports the view that, contrary to earlier predictions, ACE inhibitors are at least as effective in elderly hypertensive patients as in younger patients. This may also be accompanied by a significant reduction in the number of adverse events reported, particularly in the most elderly. As age and BP are both continuous variables and are related to each other, they must be considered as continuous variables in the assessment of treatment effects. To use arbitrary definitions for the elderly (e.g. > 60 years or > 65 years) will only serve to exaggerate age-related phenomena and may lead to inappropriate recommendations for drug use.

Adverse drug reaction monitoring with angiotensin converting enzyme inhibitors: A prospective, randomized, open-label, comparative study

“…The incidence of hypotension with the use of ACEIs is reported to be in the range of 2–5% and there is no significant difference in the incidence of hypotension caused by d-ACEIs or by p-ACEIs. [ 7 9 13 14 ] However, in our study, hypotension was observed only in a few subjects receiving fosinopril that needed reduction in dosage from 10 mg/day to 5 mg/day. This feature was observed approximately after a month of starting therapy with fosinopril.…”

“…[791314] However, in our study, hypotension was observed only in a few subjects receiving fosinopril that needed reduction in dosage from 10 mg/day to 5 mg/day. This feature was observed approximately after a month of starting therapy with fosinopril.…”

“…Nausea with use of ACEIs is around 1–5% as reported in the literature. [ 7 9 13 15 ] It is somewhat higher with lisinopril as compared to enalapril and ramipril[ 7 13 15 ] and considerably low with fosinopril. [ 9 ] Our findings indicated that the incidence of nausea was higher (10%) with all three agents, namely, enalapril, lisinopril, and ramipril (d-ACEIs), whereas, none receiving fosinopril (p-ACEI) had nausea.…”

Angiotensin-Converting Enzyme Inhibitors

“…Plasma renin activity declines steadily with age 26 but the reasons for this “atrophic” pattern are not known. In drug development studies that include individuals with high diastolic BP, age is not a strong predictor of ACE inhibitor response 27 . In clinical practice, however, blunted response to ACE inhibition in older individuals is often seen.…”