When to recommend a combination of ACE-inhibitors and angiotensin receptor blockers

Authors: J. Václavík
Authors‘ workplace: I. interní klinika –  kardiologická LF UP a FN Olomouc
Published in: Kardiol Rev Int Med 2014, 16(6): 481-484
Category: Cardiology Review


ACE-inhibitors (ACE-I) and angiotensin receptor blockers (ARB) are frequently used in the treatment of arterial hypertension, coronary artery disease, heart fail­­ure, chronic kidney disease and diabetes mellitus. The combination of both drug classes in hypertension leads to a small additional blood pressure reduction, but does not lower the rate of cardiovascular events and has more complications, and therefore is now no longer recommended. Because of the increased number of complications, the combination of ACE-I and ARB is also not recommended in patients with coronary artery disease and chronic kidney disease. This combination is also being used less frequently in heart failure, but is still indicated in symptomatic patients with left ventricular dysfunction who do not tolerate mineralocorticoid receptor antagonists.

ACE-inhibitors – angiotensin receptor blockers – combination – hypertension – coronary artery disease – chronic kidney disease


1. Azizi M, Linhart A, Alexander J et al. Pilot study of combined blockade of the renin‑angiotensin system in essential hypertensive patients. J Hypertens 2000; 18: 1139– 1147.

2. Stergiou GS, Skeva II, Baibas NM et al. Additive hypotensive effect of angiotensin‑converting enzyme inhibition and angiotensin‑receptor antagonism in essential hypertension. J Cardiovasc Pharmacol 2000; 35: 937– 941.

3. Izzo JL Jr, Weinberg MS, Hainer JW et al. Antihypertensive efficacy of candesartan‑lisinopril in combination vs. up- titration of lisinopril: the AMAZE trials. J Clin Hypertens (Greenwich) 2004; 6: 485– 493.

4. Doulton TW, He FJ, MacGregor GA. Systematic review of combined angiotensin‑converting enzyme inhibition and angiotensin receptor blockade in hypertension. Hypertension 2005; 45: 880– 886.

5. Yusuf S, Teo KK. Pogue J et al. ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358: 1547– 1559. doi: 10.1056/ NEJMoa0801317.

6. Mancia G, Fagard R, Narkiewicz K et al. Task Force Members. 2013 ESH/ ESC Guidelines for the ma­nagement of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013; 31: 1281– 1357. doi: 10.1097/ 01.hjh.0000431740.32696.cc.

7. Alvarez- Alvarez B, Abad- Cardiel M, Fernandez- Cruz A et al. Management of resistant arterial hypertension: role of spironolactone versus double blockade of the renin‑angiotensin‑aldosterone system. J Hypertens 2010; 28: 2329– 2335. doi: 10.1097/ HJH.0b013e32833d4c99.

8. Pfeffer MA, McMurray JJ, Velazquez EJ et al. Valsartan in Acute Myocardial Infarction Trial Investigators. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349: 1893– 1906.

9. Cohn JN, Tognoni G. Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin‑receptor blocker valsartan in chronic heart failure. N Engl J Med 2001; 345: 1667– 1675.

10. McMurray JJ, Ostergren J, Swedberg K et al. 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– 771.

11. Weir RA, McMurray JJ, Puu M et al. CHARM Investigators. Efficacy and tolerability of adding an angiotensin receptor blocker in patients with heart failure already receiving an angiotensin‑converting inhibitor plus aldosterone antagonist, with or with­out a beta blocker. Findings from the Candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM)-Added trial. Eur J Heart Fail 2008; 10: 157– 163. doi: 10.1016/ j.ejheart.2007.12.006.

12. McKelvie RS, Yusuf S, Pericak D et al. Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation 1999; 100: 1056– 1064.

13. Phillips CO, Kashani A, Ko DK et al. Adverse effects of combination angiotensin II receptor blockers plus angiotensin‑converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from randomized clinical trials. Arch Intern Med 2007; 167: 1930– 1936.

14. Dickstein K, Cohen– Solal A, Filippatos G et al. ESC Guidelines for the dia­gnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Dia­gnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Eur Heart J 2008; 29: 2388– 2442. doi: 10.1093/ eurheartj/ ehn309.

15. McMurray JJ, Adamopoulos S, Anker SD et al. ESC Guidelines for the dia­gnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Dia­gnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Eur Heart J 2012; 33: 1787– 1847. doi: 10.1093/ eurheartj/ ehs104.

16. J. Hradec, J. Vítovec, J. Špinar. Summary of the ESC Guidelines for the dia­gnosis and treatment of acute and chronic heart failure 2012. Prepared by the Czech Society of Cardiology. Cor Vasa 2013; 55: e25– e40.

17. Kunz R, Wolbers M, Glass T et al. The COOPERATE trial: a letter of concern. Lancet 2008; 371: 1575– 1576. doi: 10.1016/ S0140‑ 6736(08)60681‑ 9.

18. Parving HH, Persson F, Lewis JB et al. AVOID Study Investigators. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med 2008; 358: 2433– 2446. doi: 10.1056/ NEJMoa0708379.

19. Parving HH, Brenner BM, McMurray JJ et al. ALTITUDE Investigators. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med 2012; 367: 2204– 2213. doi: 10.1056/ NEJMoa1208799.

20. Mann JF, Schmieder RE, McQueen M et al. ONTARGET investigators. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, random­ized, double‑blind, controlled trial. Lancet 2008; 372: 547– 553. doi: 10.1016/ S0140‑ 6736(08)61236‑ 2.

21. Fried LF, Emanuele N, Zhang JH et al. VA NEPHRON- D Investigators. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med 2013; 369: 1892– 1903. doi: 10.1056/ NEJMoa1303154.

22. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. [online] Available from http:/ / www.kdigo.org/ clinical_practice_guidelines/ pdf/ CKD/ KDIGO_2012_CKD_GL.pdf.

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