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Year : 2008  |  Volume : 40  |  Issue : 2  |  Page : 91

Is the combination of enalapril and losartan irrational?

Department of Pharmacology, M.P. Shah Medical College, Jamnagar - 361 008, Gujarat, India

Correspondence Address:
D M Parmar
Department of Pharmacology, M.P. Shah Medical College, Jamnagar - 361 008, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0253-7613.41047

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How to cite this article:
Parmar D M, Jadav S P. Is the combination of enalapril and losartan irrational?. Indian J Pharmacol 2008;40:91

How to cite this URL:
Parmar D M, Jadav S P. Is the combination of enalapril and losartan irrational?. Indian J Pharmacol [serial online] 2008 [cited 2023 Sep 24];40:91. Available from: https://www.ijp-online.com/text.asp?2008/40/2/91/41047

Different views have been expressed on the topic of 'combination therapy of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB): rational or irrational?' in the form of correspondences published in the Indian Journal of Pharmacology. [1],[2],[3],[4]

The discussion on this topic started with the editorial by Gautam and Aditya in which they had suggested that the combination of enalapril and losartan is irrational. [5] Tandon, [1] Sharma et al ., [2] and Petroianu [4] have argued that the combination of ACE inhibitors and ARB is rational based on evidences obtained from clinical trials. Gautam and Aditya [3] categorized this combination as controversial rather than rational, also citing the results of related clinical trials; they had also opined that the long-awaited results of the ONTARGET (Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) may help to define clearly the status of such a combination.

The results of the ONTARGET study have been published in a recent issue of the New England Journal of Medicine; the study found that the combination of telmisartan (an ARB) and ramipril (an ACE inhibitor) was associated with more adverse events, without offering any increase in benefits. This particular combination showed higher rates of hypotensive symptoms, syncope, renal dysfunction, and hyperkalemia, with a trend toward an increased risk of renal dysfunction requiring dialysis. [6] The VALIANT (Valsartan in Acute Myocardial Infarction Trial) study showed additional adverse effects, including hypotension and renal dysfunction, with a combination of an ARB and an ACE inhibitor. [7] Both the VALIANT and the ONTARGET trials added an ARB to an evidence-based dose of an evidence-based ACE inhibitor. [8] On the other hand, two heart failure studies, namely the Valsartan Heart Failure Trial (Val-HeFT) and the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity-Added (CHARM-Added), showed that additional benefits were to be had by combining an ARB with an ACE inhibitor. [9],[10] However, in both these studies (VAL-HeFT and CHARM-Added), an ARB was combined with the physicians' choice of the type and regimen of ACE inhibitor and, therefore, whether the benefits of combination therapy observed in these studies were due to the condition studied (heart failure) or the type or regimen of the ACE inhibitor used is uncertain. [8] A meta-analysis of randomized controlled trials showed that combination therapy with an ARB plus an ACE inhibitor in subjects with symptomatic left ventricular dysfunction was accompanied by marked increases in adverse effects. [11]

To sum up, available evidence-based information indicates that the combination of an ARB and an ACE inhibitor is irrational.

  References Top

1.Tandon VR. Is enalapril and losartan combination irrational? Indian J Pharmacol 2006;38:295-6.  Back to cited text no. 1    
2.Sharma KK, Sahaya K, Mediratta PK. Is enalapril and losartan combination irrational? Indian J Pharmacol 2006;38:296.  Back to cited text no. 2    
3.Gautam CS, Aditya S. Is enalapril and losartan combination irrational? Indian J Pharmacol 2006;38:296-7.  Back to cited text no. 3    
4.Petroianu GA. Combined treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARB): 'Beating a dead horse' or meaningful mechanism-guided therapy? Indian J Pharmacol 2006;38:372-3.  Back to cited text no. 4    
5.Gautam CS, Aditya S. Irrational drug combinations: Need to sensitize undergraduates. Indian J Pharmacol 2006;38:169-70.  Back to cited text no. 5    
6.The ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547-59.  Back to cited text no. 6    
7.Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Kober L, Maggioni AP, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003;349:1893-906.  Back to cited text no. 7    
8.McMurray JJ. ACE inhibitors in cardiovascular disease-unbeatable? N Engl J Med 2008;358:1615-6.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001;345:1667-75.  Back to cited text no. 9    
10.McMurray JJ, Ostergren J, Swedberg K, Granger CB, Held P, Michelson EL, et al. 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.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Phillips CO, Kashani A, Ko DK, Francis G, Krumholz HM. Adverse effects of combination of 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;167:1930-6.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]

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