Candesartan vs losartan

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appearing in supplement issues of the Journal ... regimen in the label, the authors incorrectly chose to compare ... as having a flawed design and an improper or.
Journal of Human Hypertension (1998) 12, 419–422  1998 Stockton Press. All rights reserved 0950-9240/98 $12.00 http://www.stockton-press.co.uk/jhh

LETTERS TO THE EDITOR

Candesartan and losartan: a statement from the editor In this issue of the Journal of Human Hypertension we publish two letters concerning the contents of one of our supplement issues devoted to the topic of candesartan cilexetil.1 It must be made entirely clear that papers appearing in supplement issues of the Journal, represent the proceedings of medical and scientific conferences which often cannot be peer-reviewed using the same procedures as papers submitted for the general issues. Instead we rely on the editors of the particular supplements to ensure that all papers are of sufficient standard. The criteria for the candesartan supplement were, therefore, no different from those applied to the losartan supplement we published in 1995.2 DG Beevers References 1 Andersson OK, Neldam S. A comparison of the antihypertensive effects of candesartan cilexetil and losartan in patients with mild to moderate hypertension. J Hum Hypertens 1997; 11 (Suppl 2): 63–64. 2 Conference Proceedings: The role of losartan in anti-hypertensive therapy. J Hum Hypertens 1995; 9 (Suppl 5): 1–58.

Candesartan vs losartan In the recent article by Andersson and Neldam comparing the antihypertensive effect and tolerability of candesartan cilexetil 8 and 16 mg once-daily with that of losartan 50 mg and of placebo once-daily in patients with mild to moderate primary hypertension, the authors concluded: ‘Candesartan cilexetil 16 mg is significantly more effective than losartan 50 mg once-daily, 24 h after dose administration.’1 We

believe a number of potentially serious errors have been made in this study. The losartan monotherapy dosages used in this comparison were not selected in accordance with the product circular of losartan in Sweden and Denmark, which recommends: ‘The usual starting and maintenance dose is 50 mg once daily for most patients. The maximal anti-hypertensive effect is attained 3–6 weeks after initiation of therapy. Some patients may receive an additional benefit by increasing the dose to 100 mg once daily.’2 Instead of using losartan according to the approved dosing regimen in the label, the authors incorrectly chose to compare both the candesartan 8 mg starting dose and the 16 mg maximum dose of candesartan to the starting dose of losartan (50 mg) only. Furthermore, the trial was designed as a randomised, placebo-controlled trial. The losartan used in the study was blinded and differed from marketed losartan in two significant respects. First, the marketed losartan tablet was encapsulated in a gelatin capsule. Second, the gelatin capsule was backfilled with microcrystalline cellulose. These blinding methods constitute a significant change in composition. Andersson and Neldam are now claiming superiority of candesartan over losartan. This should require full bioequivalence testing to demonstrate that the encapsulation of losartan did not alter the efficacy. Upon encapsulation of the losartan tablets to ensure blinding, bioequivalence with the original gelanic form was not performed, as mandated by ‘The Rules Governing Medicinal Products in the European Community.’3 Therefore, the study may be flawed and the conclusions invalid. In conclusion, we believe the data presented by Andersson and Neldam may be flawed and misleading and therefore should not

form the basis for treatment decisions by clinicians. T Bunt, MD A Dumaswala One Merck Drive Merck & Co Inc PO Box 100, WS3C-60 Whitehouse Station NJ 08889-0100 USA References 1 Andersson OK, Neldam S. A comparison of the antihypertensive effects of candesartan cilexetil and losartan in patients with mild to moderate hypertension. J Hum Hypertens 1997; 11 (Suppl 2): 63–64. 2 Product Circular for Cozaar (WPC-CZRT-0497) in Sweden and Denmark. 3 The Rules Governing Medicinal Products in the European Community, Volume II, pp 159–161.

Candesartan cilexetil vs losartan In the letter from Merck & Co, Inc, our candesartan vs losartan comparison published as a short communication in the Journal of Human Hypertension is criticised as having a flawed design and an improper or non-validated method for blinding.1 With respect to the study design, we chose to compare candesartan cilexetil with the standard dose of losartan, which is 50 mg once daily. The main reason is that a flat dose-response curve of losartan has been demonstrated in several studies sponsored by Merck, showing that no additional effect compared with 50 mg is attained at doses of 100 mg and 150 mg,2 and later confirmed by Ikeda et al.3 Although it is possible that few individual patients could derive a greater effect from the 100 mg tablet, the literature is consistent in showing the lack of better antihyperensive effect with this dose