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      Critical review of cancer risk associated with angiotensin receptor blocker therapy

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          Abstract

          The role of drugs in new cancer occurrence and cancer-related death is a major concern. Recently, a meta-analysis raised the possibility that angiotensin receptor blockers (ARBs) might have an adverse effect on patients. This generated a significant debate until the publication of two further meta-analyses, neither of which demonstrated an increased risk of new cancer occurrence or cancer-related death with the use of ARBs in patients with hypertension, heart failure, and/or nephropathy. This illustrates that the results of meta-analyses should be interpreted cautiously and critically as bias, such as selection bias, might lead to erroneous conclusions. Overall, the bulk of evidence today indicates that ARBs are not associated with increased cancer risk.

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          Most cited references57

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          The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes.

          Microalbuminuria and hypertension are risk factors for diabetic nephropathy. Blockade of the renin-angiotensin system slows the progression to diabetic nephropathy in patients with type 1 diabetes, but similar data are lacking for hypertensive patients with type 2 diabetes. We evaluated the renoprotective effect of the angiotensin-II-receptor antagonist irbesartan in hypertensive patients with type 2 diabetes and microalbuminuria. A total of 590 hypertensive patients with type 2 diabetes and microalbuminuria were enrolled in this multinational, randomized, double-blind, placebo-controlled study of irbesartan, at a dose of either 150 mg daily or 300 mg daily, and were followed for two years. The primary outcome was the time to the onset of diabetic nephropathy, defined by persistent albuminuria in overnight specimens, with a urinary albumin excretion rate that was greater than 200 microg per minute and at least 30 percent higher than the base-line level. The base-line characteristics in the three groups were similar. Ten of the 194 patients in the 300-mg group (5.2 percent) and 19 of the 195 patients in the 150-mg group (9.7 percent) reached the primary end point, as compared with 30 of the 201 patients in the placebo group (14.9 percent) (hazard ratios, 0.30 [95 percent confidence interval, 0.14 to 0.61; P< 0.001] and 0.61 [95 percent confidence interval, 0.34 to 1.08; P=0.081 for the two irbesartan groups, respectively). The average blood pressure during the course of the study was 144/83 mm Hg in the placebo group, 143/83 mm Hg in the 150-mg group, and 141/83 mm Hg in the 300-mg group (P=0.004 for the comparison of systolic blood pressure between the placebo group and the combined irbesartan groups). Serious adverse events were less frequent among the patients treated with irbesartan (P=0.02). Irbesartan is renoprotective independently of its blood-pressure-lowering effect in patients with type 2 diabetes and microalbuminuria.
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            Effect of Enalapril on Mortality and the Development of Heart Failure in Asymptomatic Patients with Reduced Left Ventricular Ejection Fractions

            New England Journal of Medicine, 327(10), 685-691
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              Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial.

              Angiotensin II type 1 receptor blockers have favourable effects on haemodynamic measurements, neurohumoral activity, and left-ventricular remodelling when added to angiotensin-converting-enzyme (ACE) inhibitors in patients with chronic heart failure (CHF). We aimed to find out whether these drugs improve clinical outcome. Between March, 1999, and November, 1999, we enrolled 2548 patients with New York Heart Association functional class II-IV CHF and left-ventricular ejection fraction 40% or lower, and who were being treated with ACE inhibitors. We randomly assigned patients candesartan (n=1276, target dose 32 mg once daily) or placebo (n=1272). At baseline, 55% of patients were also treated with beta blockers and 17% with spironolactone. The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF. Analysis was done by intention to treat. The median follow-up was 41 months. 483 (38%) patients in the candesartan group and 538 (42%) in the placebo group experienced the primary outcome (unadjusted hazard ratio 0.85 [95% CI 0.75-0.96], p=0.011; covariate adjusted p=0.010). Candesartan reduced each of the components of the primary outcome significantly, as well as the total number of hospital admissions for CHF. The benefits of candesartan were similar in all predefined subgroups, including patients receiving baseline beta blocker treatment. The addition of candesartan to ACE inhibitor and other treatment leads to a further clinically important reduction in relevant cardiovascular events in patients with CHF and reduced left-ventricular ejection fraction.
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                Author and article information

                Journal
                Vasc Health Risk Manag
                Vascular Health and Risk Management
                Vascular Health and Risk Management
                Dove Medical Press
                1176-6344
                1178-2048
                2011
                2011
                12 December 2011
                : 7
                : 741-747
                Affiliations
                [1 ]Service of Nephrology and Hypertension Consultation, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
                [2 ]Division of Clinical Pathophysiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
                [3 ]Clinical Research Centre, Unil/Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
                Author notes
                Correspondence: Bernard Waeber, Division de Physiopathologie Clinique, Centre Hostpitalier Universitaire Vaudois, 1011 Lausanne, Switzerland, Tel +41 21 314 14 31, Fax +41 21 314 14 32, Email bernard.waeber@ 123456chuv.ch
                Article
                vhrm-7-741
                10.2147/VHRM.S13552
                3253767
                22241948
                a49088d7-449d-4148-bfe6-607acfd85340
                © 2011 Wuerzner et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                Categories
                Review

                Cardiovascular Medicine
                angiotensin receptor blocker,cancer,meta-analyses,hypertension
                Cardiovascular Medicine
                angiotensin receptor blocker, cancer, meta-analyses, hypertension

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