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Effect of candesartan and lisinopril alone and in combination on blood pressure and microalbuminuria
Trefor Morgan
Department of Physiology, University of Melbourne, Victoria, 3010, Australia, treforom{at}unimelb.edu.au, Hypertension Clinic, ARMC, Heidelberg, Victoria, 3084, Australia
Adrianne Anderson
Hypertension Clinic, ARMC, Heidelberg, Victoria, 3084, Australia
Denise Bertram
Hypertension Clinic, ARMC, Heidelberg, Victoria, 3084, Australia
Robert Jeffrey MacInnis
Department of Physiology, University of Melbourne, Victoria, 3010, Australia
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.
Conclusion
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.
Key Words: ACE inhibitors • AT1-receptor blockers • microalbuminuria • renin • angiotensin • candesartan • lisinopril
References
- Garg R., Yusuf S., for the Collaborative Group on ACE Inhibitor Trials. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. JAMA 1995;273:1450-6.[Abstract/Free Full Text]
- GradmanAH,Arcuri KE, Goldberg AL et al.A randomized, placebo-controlled, double-blind, parallel study of various doses of losartan potassium compared with enalapril maleate in patients with essential hypertension. Hypertension 1995; 25:1345-50.[Abstract/Free Full Text]
- Lacourcière Y., Asmar R., for the Candesartan /Losartan Study Investigators. A comparison of the efficacy and duration of action of candesartan cilexetil and losartan as assessed by clinic and ambulatory blood pressure after a missed dose, in truly hypertensive patients: A placebo-controlled, forced titration study. Am J Hypertens 1999;12:1181-7.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Wing LMH, Reid CM, Ryan P. et al. for the Second Australian National Blood Pressure Study Group.A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med 2003;348:583-92.[Abstract/Free Full Text]
- Dahlöf B., Devereux RB, Kheldsen SE et al. for the LIFE Study Group. Cardiovascular morbidity and mortality in Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet 2002; 359:995-1003.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high risk patients. N Engl J Med 2000;342:142-53.
- Moldenhauer GK, Smith MD, Di Nicolantonio R., Doyle AE, Morgan TO Angiotensins II and III prevent captopril-induced renin release in the rat. Clin Exp Pharmacol Physiol 1988;15: 113-21.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Morsing P., Adler G., Brandt-Eliasson U. et al. Mechanistic differences of various AT1-receptor blockers in isolated vessels of different origin. Hypertension 1999;33:1406-13.[Abstract/Free Full Text]
- Vanderheyden PML, Fierens FL, De Backer JP, Vauquelin G. Reversible and syntopic interaction between angiotensin receptor antagonists on Chinese hampster ovary cells expressing human angiotensin II type I receptors. Biochem Pharmacol 2000;59:927-35.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Mogensen CE, Neldam S., Tikkanen I. et al. Randomized controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ 2000;321:1440-4.[Abstract/Free Full Text]
- Morgan T., Griffiths C., Delbridge L. Interaction of ACE inhibitors and AT1-receptor blockers on maximum blood pressure response in spontaneous hypertensive rats. JRAAS 2002;3:16-18.[Medline]
[Order article via Infotrieve]
- Morgan T., Griffiths C., Delbridge L. Low doses of angiotensin converting enzyme inhibitors and angiotensin Type 1 blockers have a synergistic effect but high doses are less than additive. Am J Hypertens 2002;15:1003-05.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- van Kats JP, Danser AH, van Meegen JR, Sassen LM, Verdouw PD, Schalekamp MA Angiotensin production by the heart: a quantitative study in pigs with the use of radiolabeled angiotensin infusions. Circulation 1998;98:73-81.[Abstract/Free Full Text]
- Urata H., Kinoshita A., Misono KS, Bumpus FM, Husain A. Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart. J Biol Chem 1990;265:22348-57.[Abstract/Free Full Text]
- Sever PS, Chang CL Discordant responses to two classes of drugs acting on the renin-angiotensin system. JRAAS 2001;2(1):25-30.[Medline]
[Order article via Infotrieve]
- Morgan T., Anderson A. A comparison of candesartan, felodipine and their combination in the treatment of elderly patients with systolic hypertension. Am J Hypertens 2002; 15(6):544-9.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Morgan TO,Anderson A., Jones E. Comparison and interaction of low dose felodipine (ER) and enalapril in the treatment of essential hypertension in elderly patients. Am J Hypertens 1992;5:238-43.[Web of Science][Medline]
[Order article via Infotrieve]
- Griffiths CD, Morgan TO, Delbridge LMD. Effects of combined administration of ACE inhibitor and angiotensin II receptor antagonist are prevented by a high NaCl intake. J Hypertens 2001;19:2087-95.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Morgan T., Griffiths C., Delbridge L. Wall stress, angiotensin II and left ventricular hypertrophy. In: Epstein M, Brunner H, editors. Angiotensin II receptor antagonists. Philadelphia: Hanley & Belfus; 2000. p. 223-34.
- McMurrary JVJ, Östergren J., Swedberg K. et al. for the CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003;362:767-71.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Rossing K., Jacobsen P., Pietraszek L., H-H. Parving. Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy. Diabetes Care 2003;26:2268-74.[Abstract/Free Full Text]
- Kincaid-Smith P., Fairley K., Packham D. Randomized controlled crossover study of the effect on proteinuria and blood pressure of adding an angiotensin II receptor antagonist to an angiotensin converting enzyme inhibitor in normotensive patients with chronic renal disease and proteinuria. Nephrol Dial Transplant 2002;17:597-601.[Abstract/Free Full Text]
- Komine N., Khang S.,Wead LM, Blantz RC, Gabbai FB Effect of combining an ACE inhibitor and an angiotensin II receptor blocker on plasma and kidney tissue angiotensin II levels. Am J Kidney Dis 2002;39:159-64.[Web of Science][Medline]
[Order article via Infotrieve]
- Azizi M., Bissery A., Bura-Rivière A., Ménard J. Dual renin-angiotensin system blockade restores blood pressure-renin dependency in individuals with low renin concentrations. J Hypertens 2003;21:1887-95.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
Journal of Renin-Angiotensin-Aldosterone System, Vol. 5, No. 2,
64-71 (2004)
DOI: 10.3317/jraas.2004.012
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