Candesartan-Based Therapy and Risk of Cancer in Patients With Systemic Hypertension (Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease [HIJ-CREATE] Substudy)

Published:November 18, 2011DOI:
      The aim of the present study was to clarify the influence of candesartan-based therapy on subsequent carcinogenesis and cancer death in patients with coronary artery disease with hypertension in a substudy of a multicenter, prospective, randomized, controlled trial. That trial compared the effects of candesartan-based therapy with those of non-angiotensin receptor blocker (ARB)-based standard therapy on major adverse cardiovascular events. Hypertensive patients with coronary artery disease were randomly assigned to receive either candesartan-based (n = 1,024) or non–ARB-based pharmacotherapy, including angiotensin-converting enzyme inhibitors (n = 1,025). During a median follow-up of 4.2 years, 1,606 adverse events (798 in the candesartan group and 808 in the non-ARB standard group) were reported. Among them, new cancer occurred in 5.37% of subjects in the candesartan group and 5.66% of subjects in the standard therapy group (hazard ratio 0.95, 95% confidence interval 0.65 to 1.38). Cancer deaths occurred in 1.66% in the candesartan group and 2.44% in the standard therapy group, respectively (hazard ratio 0.74, 95% confidence interval 0.39 to 1.39). Kaplan-Meier estimates of survival without new cancer and cancer deaths demonstrated that candesartan-based therapy does not accelerate the occurrence of new cancer (log-rank, p = 0.84) or cancer death (p = 0.39) compared to standard therapy. Advanced age and male gender were independently and significantly correlated with the subsequent incidence of cancer. In conclusion, the results of the present study suggest that candesartan-based therapy is not associated with either carcinogenesis or cancer death compared to non-ARB standard therapy.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Sipahi I.
        • Debanne S.M.
        • Rowland D.Y.
        • Simon D.I.
        • Fang J.C.
        Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials.
        Lancet Oncol. 2010; 11: 627-636
        • Bangalore S.
        • Kumar S.
        • Kjeldsen S.E.
        • Makani H.
        • Grossman E.
        • Wetterslev J.
        • Gupta A.K.
        • Sever P.S.
        • Gluud C.
        • Messerli F.H.
        Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials.
        Lancet Oncol. 2011; 12: 65-82
        • Pasternak B.
        • Svanström H.
        • Callréus T.
        • Melbye M.
        • Hviid A.
        Use of angiotensin receptor blockers and the risk of cancer.
        Circulation. 2011; 123: 1729-1736
        • Huang C.C.
        • Chan W.L.
        • Chen Y.C.
        • Chen T.J.
        • Lin S.J.
        • Chen J.W.
        • Leu H.B.
        Angiotensin II receptor blockers and risk of cancer in patients with systemic hypertension.
        Am J Cardiol. 2011; 107: 1028-1033
        • Kasanuki H.
        • Hagiwara N.
        • Hosoda S.
        • Sumiyoshi T.
        • Honda T.
        • Haze K.
        • Nagashima M.
        • Yamaguchi J.
        • Origasa H.
        • Urashima M.
        • Ogawa H.
        • HIJ-CREATE Investigators
        Angiotensin II receptor blocker-based vs. non-angiotensin II receptor blocker-based therapy in patients with angiographically documented coronary artery disease and hypertension: the Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease (HIJ-CREATE).
        Eur Heart J. 2009; 30: 1203-1212
        • Lever A.F.
        • Hole D.J.
        • Gillis C.R.
        • McCallum I.R.
        • McInnes G.T.
        • MacKinnon P.L.
        • Meredith P.A.
        • Murray L.S.
        • Reid J.L.
        • Robertson J.W.
        Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer?.
        Lancet. 1998; 352: 179-184
        • Fujita M.
        • Hayashi I.
        • Yamashina S.
        • Itoman M.
        • Majima M.
        Blockade of angiotensin AT1a receptor signaling reduces tumor growth, angiogenesis, and metastasis.
        Biochem Biophys Res Commun. 2002; 294: 441-447
        • Egami K.
        • Murohara T.
        • Shimada T.
        • Sasaki K.
        • Shintani S.
        • Sugaya T.
        • Ishii M.
        • Akagi T.
        • Ikeda H.
        • Matsuishi T.
        • Imaizumi T.
        Role of host angiotensin II type 1 receptor in tumor angiogenesis and growth.
        J Clin Invest. 2003; 112: 67-75
        • Miyajima A.
        • Kosaka T.
        • Asano T.
        • Asano T.
        • Seta K.
        • Kawai T.
        • Hayakawa M.
        Angiotensin II type I antagonist prevents pulmonary metastasis of murine renal cancer by inhibiting tumor angiogenesis.
        Cancer Res. 2002; 62: 4176-4179
        • Teo K.K.
        • Sleight P.
        • Gao P.
        • Yusuf S.
        Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138,769 individuals.
        J Hypertens. 2011; 29: 623-635
        • Chang C.H.
        • Lin J.W.
        • Wu L.C.
        • Lai M.S.
        Angiotensin receptor blockade and risk of cancer in type 2 diabetes mellitus: a nationwide case-control study.
        J Clin Oncol. 2011; 29: 3001-3007
        • Matsuda T.
        • Marugame T.
        • Kamo K.
        • Katanoda K.
        • Ajiki W.
        • Sobue T.
        • Japan Cancer Surveillance Research Group
        Cancer incidence and incidence rates in Japan in 2005: based on data from 12 population-based cancer registries in the Monitoring of Cancer Incidence in Japan (MCIJ) project.
        Jpn J Clin Oncol. 2011; 41: 139-147