Effect of candesartan and lisinopril alone and in combination on blood pressure and microalbuminuria.
BACKGROUND
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blocking drugs (ARB) block the effect of angiotensin II by different mechanisms. It has been suggested that combined therapy may be more effective at reducing blood pressure (BP) than higher doses of either drug.


METHODS
Twenty-three elderly patients with systolic hypertension completed a double-blind crossover study comparing placebo, candesartan (C) 16 mg, C32 mg, lisinopril (L) 20 mg, L40 mg and C16 mg + L20 mg. Treatment periods were one month and ambulatory BP measurements were performed at the end of each period. The effects on albumin excretion in eight patients with microalbuminuria were determined.


RESULTS
All treatments lowered BP. The falls in systolic and diastolic BP with C16, C32, L20 and L40 were similar. Plasma renin rose to a similar extent. A plateau effect was reached with C16 and L20. Systolic BP on the combination of C16 + L20 was lower than on each monotherapy (C16, 3.8 mmHg [p=0.002]; C32, 6.4 [0.0003]; L20, 2.9 [0.05]; L40, 3.3 [0.003]). The additional fall in BP with the combination appeared to be due to recruitment of non-responders, rather than to an additive effect in most patients. All treatments reduced microalbuminuria to a similar extent. The combination was well tolerated and there was no deterioration in renal function.


CONCLUSIONS
When patients are on a plateau dose of an ACE inhibitor or an ARB, addition of the other drug class has a small but significant incremental effect on BP in the overall group. However, some patients respond better to one drug class than to the other and this may explain the results. This study lends no support to the use of these two drugs in combination to treat hypertension.
Department of Physiology, University of Melbourne, Victoria, 3010, Australia. treforom@unimelb.edu.au
Trefor
T
Morgan
Adrianne
A
Anderson
Denise
D
Bertram
Robert Jeffrey
RJ
MacInnis
D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000188:drug therapy*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D017706:Lisinopril / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D017706:Lisinopril; C081643:candesartan