|
Sign In to gain access to subscriptions and/or personal tools.
|
Discordant responses to two classes of drugs acting on the renin-angiotensin system
Peter S Sever
Clinical Pharmacology, Imperial College School of Medicine, NHLI Division, St Mary's Hospital, London W2 1NY UK, p.sever{at}ic.ac.uk
C. Limmie Chang
Clinical Pharmacology, Imperial College School of Medicine, NHLI Division, St Mary's Hospital, London W2 1NY UK
Introduction
Marked heterogeneity characterises blood pressure (BP) responses to antihypertensive drugs. The efficacy of drugs acting on the renin-angiotensin-aldosterone system (RAAS) is predicted (albeit weakly) by plasma renin activity (PRA) and it has been assumed that, within individuals, there would be concordance in efficacy between drugs acting at different sites to block the RAAS.
Design
The present study was a randomised, double-blind, two-way, crossover study designed to evaluate intra-individual BP responses to an angiotensin II AT1receptor blocker (ARB), candesartan cilexetil, and an angiotensin-converting enzyme inhibitor (ACE-I), lisinopril, and to identify potential phenotypic characteristics of patients' responses to the drugs.
Methods
92 patients with essential hypertension, (mean systolic/diastolic BP 160/101 mmHg) entered the trial, of whom 76 patients completed both treatments.
Results
There was marked heterogeneity in response to the two drugs. 50% of patients responded (fall in diastolic BP of >10 mmHg or achieved diastolic pressure <90 mmHg) to both drugs; 16% were non-responders to both drugs; 20% responded to the ACE-I but not the ARB and 15% responded to the ARB but not to the ACE-I. Individual responses to the two drugs were poorly correlated (for diastolic pressure: r=0.19, p=0.11; for systolic pressure: r=-0.01, p=0.92). For the ACE-I, the fall in both systolic and diastolic BP was related to pretreatment PRA (for diastolic pressure: r=0.31, p=0.008; for systolic pressure: r=0.24, p=0.04). In the case of the ARB, no relationship between the fall in BP and PRA was observed.
These observations suggest that more complex mechanisms may be involved in BP reduction with ARBs than with ACE-I.
Key Words: hypertension • angiotensin converting-enzyme inhibitor • angiotensin receptor antagonist
References
- Prescott-Clarke P., Primatesta P. The Health Survey for England 1996. London, HMSO:1998.
- Sever PS The heterogeneity of hypertension. Eur Heart J 1999;1(Suppl L):L10-3.
- Materson BJ, Reda DJ, Cushman WC et al. Single drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. New Eng J Med 1993;328:914-21.[Abstract/Free Full Text]
- The Sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Arch Intern Med 1997;157:2413-46.[Abstract/Free Full Text]
- 1999 World Health Organisation - International Society of Hypertension Guidelines for the Management of Hypertension. Guidelines Sub-committee.JHypertens 1999;17:151-83.
- Ramsay LE, Williams B., Johnston GD et al. for the British Hypertension Society. Guidelines for management of hypertension: report of the third working party of the British Hypertension Society. Br Med J 1999;319:630-5.[Free Full Text]
- Jones JK, Gorkin L., Lian JF, Staffa JA, Fletcher AP Discontinuation of and changes in treatment after start of new courses of antihypertensive drugs: a study of a United Kingdom population. Br Med J 1995;311:293-5.[Abstract/Free Full Text]
- Neutal JM Safety and efficacy of angiotensin II receptor antagonists. Am J Cardiol 1999; 84(suppl 2):13K-17K.[Web of Science][Medline]
[Order article via Infotrieve]
- Birkinhager WH, de Leeuw PW Non-peptide angiotensin type 1 receptor antagonists in the treatment of hypertension. J Hypertens 1999;17:873-81.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Menard J. and Catt, KJ Measurement of renin activity, concentration and substrate in rat plasma by radioimmunoassay of Angiotensin I. Endocrinology 1972; 90:422-30.[Abstract/Free Full Text]
- McNemar Q. Note on the sampling error of the differences between correlated proportions or percentages. Psychometrika. 1947;12:153-7.[CrossRef][Web of Science]
- Hills M.,Armitage P. The two-period-cross-over clinical trial. Br J Clin Pharmac. 1979;8:7-19.[Web of Science][Medline]
[Order article via Infotrieve]
- Gill JS, Zezulka AV, Beevers DG, Davis P. Relation between initial blood pressure and its fall with treatment. Lancet 1985;i:567-69.
- Dickerson JE, Hingorani AD, Ashby MJ, Palmer CR, Brown MJ Optimisation of antihypertensive treatment by crossover rotation of four major classes. Lancet 1999;353:2008-13.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Attwood S., Bird R., Burch K. et al. Within-patient correlation between the antihypertensive effects of atenolol, lisinopril and nifedipine. J Hypertens 1994;12:223-6.
- Johnston C.l, Burrell LM Evolution of the blockade of the renin-angiotensin system. J Human Hypertens 1995;9:375-80.[Web of Science][Medline]
[Order article via Infotrieve]
- Juillerat L., Nussberger J., Menard J. et al. Determinants of angiotensin II generation during converting enzyme inhibition. Hypertension 1990;16:564-72.[Abstract/Free Full Text]
- Siragy HM, de Gasparo M., Carey RM Angiotensin type 2 receptor mediates valsartan-induced hypotension in conscious rats. Hypertension 2000;35:1074-84.[Abstract/Free Full Text]
Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1,
25-30 (2001)
DOI: 10.3317/jraas.2001.004
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
|
|
