Inpharma 1647 - 19 Jul 2008

Candesartan cilexetil can make adifference to MACE rates

European guidelines recommend the use ofangiotensin II receptor antagonists (angiotensin receptorblockers [ARBs]) and ACE inhibitors in hypertensivepatients with renal impairment, and the combination ofan angiotensin II receptor antagonist plus a calciumchannel antagonist in high-risk hypertensive patients,especially those with coronary artery disease (CAD).However, questions remain over the ability of thesetherapies to prevent major adverse cardiovascularevents (MACEs). The HIJ-CREATE* investigatorsattempted to answer these questions by completingfurther analyses of their study data, focussing on theARB, candesartan cilexetil.1,2 The findings werepresented at Hypertension 2008.**

HIJ-CREATE was a multicentre, randomised, open-label, blinded-endpoint study, in which2049 hypertensive patients (aged 20–80 years) withangiographically documented CAD were randomised toreceive candesartan-based therapy (n = 1024) withoutother renin-angiotensin system inhibitors or non-ARB-based standard therapy; the aim was to achieve atarget BP of < 130/85mm Hg. Standard backgroundtherapy did not differ between the two groups.

The primary study endpoint was the incidence ofMACEs, including death from cardiovascular (CV)causes, non-fatal myocardial infarction, unstable anginapectoris (USAP), or heart failure, stroke or otherCV events requiring hospitalisation.

Benefits in renal dysfunctionA post hoc analysis of the 1151 patients with impaired

renal function (creatinine clearance < 60mL/min) wasconducted; 509 received treatment with candesartan,and 513 with non-ARB treatment, including 362 whoreceived an ACE inhibitor.1

Over the median follow-up period of 4.3 years, theMACE risk was significantly reduced by 26% withcandesartan, compared with ACE inhibitor-basedtherapy. Notably, candesartan was associated with asignificant 29% reduction in the risk of USAP requiringhospitalisation.

Calcium channel antagonists efficacyenhanced

In a subgroup analysis of the 388 patients beingtreated with amlodipine at baseline, candesartan alsohad positive effects.2

After a median follow-up of 4.1 years, the MACE riskwas significantly reduced by 39% in the patients treatedwith candesartan plus amlodipine, compared with thosenot receiving candesartan; again, a significant reductionin the incidence of USAP requiring hospitalisation wasalso noted.* Heart Institute of Japan-Candesartan Randomized trial for Evaluationin Coronary Artery Disease** 18th European Meeting on Hypertension and the 22nd ScientificMeeting of the International Society of Hypertension

1. Yagi M, et al. Effect of ARB-based vs ACEI-based therapy on cardiovascularevents in hypertensive patients with coronary artery disease and impaired renalfunction: a post hoc analysis of the HIJ-CREATE study. Journal of Hypertension26 (Suppl. 1): 440 abstr. PS31/THU/24, 2008.

2. Yamaguchi J-I, et al. Effect of combination therapy with amlodipine andcandesartan on cardiovascular events in hypertensive patients with coronaryartery disease: a subgroup analysis of the HIJ-CREATE study. Journal ofHypertension 26 (Suppl. 1): 464-465 abstr. PS32/WED/59, 2008.

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Inpharma 19 Jul 2008 No. 16471173-8324/10/1647-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved