Discordant responses to two classes of drugs acting on the renin-angiotensin system.
BACKGROUND
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.


METHODS
The present study was a randomised, double-blind,two-way, crossover study designed to evaluate intra-individual BP responses to an angiotensin II AT -receptor blocker (ARB), candesartan cilexetil, and anangiotensin-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 pre-treatment 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.
Sever
P S
PS
Clinical Pharmacology, Imperial College School of Medicine, NHLI Division, St Mary's Hospital, London, W2 1NY, UK. p.sever@ic.ac.uk
Chang
C L
CL
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D003971:Diastole; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013599:Systole; D013777:Tetrazoles
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D017706:Lisinopril; D012083:Renin; C077793:candesartan cilexetil