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      Antihypertensive efficacy of the angiotensin receptor blocker azilsartan medoxomil compared with the angiotensin-converting enzyme inhibitor ramipril

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          Abstract

          Drug therapy often fails to control hypertension. Azilsartan medoxomil (AZL-M) is a newly developed angiotensin II receptor blocker with high efficacy and good tolerability. This double-blind, controlled, randomised trial compared its antihypertensive efficacy and safety vs the angiotensin-converting enzyme inhibitor ramipril (RAM) in patients with clinic systolic blood pressure (SBP) 150–180 mm Hg. Patients were randomised ( n=884) to 20 mg AZL-M or 2.5 mg RAM once daily for 2 weeks, then force-titrated to 40 or 80 mg AZL-M or 10 mg RAM for 22 weeks. The primary endpoint was change in trough, seated, clinic SBP. Mean patient age was 57±11 years, 52.4% were male, 99.5% were Caucasian. Mean baseline BP was 161.1±7.9/94.9±9.0 mm Hg. Clinic SBP decreased by 20.6±0.95 and 21.2±0.95 mm Hg with AZL-M 40 and 80 mg vs12.2±0.95 mm Hg with RAM ( P<0.001 for both AZL-M doses). Adverse events leading to discontinuation were less frequent with AZL-M 40 and 80 mg (2.4% and 3.1%, respectively) than with RAM (4.8%). These data demonstrated that treatment of stage 1–2 hypertension with AZL-M was more effective than RAM and better tolerated.

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          Most cited references22

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          2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension.

          Hypertension is estimated to cause 4.5% of current global disease burden and is as prevalent in many developing countries, as in the developed world. Blood pressure-induced cardiovascular risk rises continuously across the whole blood pressure range. Countries vary widely in capacity for management of hypertension, but worldwide the majority of diagnosed hypertensives are inadequately controlled. This statement addresses the ascertainment of overall cardiovascular risk to establish thresholds for initiation and goals of treatment, appropriate treatment strategies for non-drug and drug therapies, and cost-effectiveness of treatment. Since publication of the WHO/ISH Guidelines for the Management of Hypertension in 1999, more evidence has become available to support a systolic blood pressure threshold of 140 mmHg for even 'low-risk' patients. In high-risk patients there is evidence for lower thresholds. Lifestyle modification is recommended for all individuals. There is evidence that specific agents have benefits for patients with particular compelling indications, and that monotherapy is inadequate for the majority of patients. For patients without a compelling indication for a particular drug class, on the basis of comparative trial data, availability, and cost, a low dose of diuretic should be considered for initiation of therapy. In most places a thiazide diuretic is the cheapest option and thus most cost effective, but for compelling indications where other classes provide additional benefits, even if more expensive, they may be more cost effective. In high-risk patients who attain large benefits from treatment, expensive drugs may be cost effective, but in low-risk patients treatment may not be cost-effective unless the drugs are cheap.
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            Hypertension prevalence and blood pressure levels in 6 European countries, Canada, and the United States.

            Geographic variations in cardiovascular disease (CVD) and associated risk factors have been recognized worldwide. However, little attention has been directed to potential differences in hypertension between Europe and North America. To determine whether higher blood pressure (BP) levels and hypertension are more prevalent in Europe than in the United States and Canada. Sample surveys that were national in scope and conducted in the 1990s were identified in Germany, Finland, Sweden, England, Spain, Italy, Canada, and the United States. Collaborating investigators provided tabular data in a consistent format by age and sex for persons at least 35 years of age. Population registries were the main basis for sampling. Survey sizes ranged from 1800 to 23 100, with response rates of 61% to 87.5%. The data were analyzed to provide age-specific and age-adjusted estimates of BP and hypertension prevalence by country and region (eg, European vs North American). Blood pressure levels and prevalence of hypertension in Europe, the United States, and Canada. Average BP was 136/83 mm Hg in the European countries and 127/77 mm Hg in Canada and the United States among men and women combined who were 35 to 74 years of age. This difference already existed among younger persons (35-39 years) in whom treatment was uncommon (ie, 124/78 mm Hg and 115/75 mm Hg, respectively), and the slope with age was steeper in the European countries. For all age groups, BP measurements were lowest in the United States and highest in Germany. The age- and sex-adjusted prevalence of hypertension was 28% in the North American countries and 44% in the European countries at the 140/90 mm Hg threshold. The findings for men and women by region were similar. Hypertension prevalence was strongly correlated with stroke mortality (r = 0.78) and more modestly with total CVD (r = 0.44). Despite extensive research on geographic patterns of CVD, the 60% higher prevalence of hypertension in Europe compared with the United States and Canada has not been generally appreciated. The implication of this finding for national prevention strategies should be vigorously explored.
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              Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis.

              The effect of different classes of antihypertensive drugs on incident diabetes mellitus is controversial because traditional meta-analyses are hindered by heterogeneity across trials and the absence of trials comparing angiotensin-converting-enzyme (ACE) inhibitors with angiotensin-receptor blockers (ARB). We therefore undertook a network meta-analysis, which accounts for both direct and indirect comparisons to assess the effects of antihypertensive agents on incident diabetes. We undertook a systematic review up to Sept 15, 2006, and identified 48 randomised groups of 22 clinical trials with 143,153 participants who did not have diabetes at randomisation and so were eligible for inclusion in our analysis. 17 trials enrolled patients with hypertension, three enrolled high-risk patients, and one enrolled those with heart failure. The main outcome was the proportion of patients who developed diabetes. Initial drug therapy used in the trials (and the number of patients with diabetes of the total number at risk) included: an ARB (1189 of 14,185, or 8.38%), ACE inhibitor (1618 of 22,941, or 7.05%), calcium-channel blocker (CCB, 2791 of 38,607, or 7.23%), placebo (1686 of 24,767, or 6.81%), beta blocker (2705 of 35,745, or 7.57%), or diuretic (998 of 18,699, or 5.34%). With an initial diuretic as the standard of comparison (eight groups), the degree of incoherence (a measure of how closely the entire network fits together) was small (omega=0.000017, eight degrees of freedom). The odds ratios were: ARB (five groups) 0.57 (95% CI 0.46-0.72, p<0.0001); ACE inhibitor (eight groups) 0.67 (0.56-0.80, p<0.0001); CCB (nine groups): 0.75 (0.62-0.90, p=0.002); placebo (nine groups) 0.77 (0.63-0.94, p = 0.009); beta blocker (nine groups) 0.90 (0.75-1.09, p=0.30). These estimates changed little in many sensitivity analyses. The association of antihypertensive drugs with incident diabetes is therefore lowest for ARB and ACE inhibitors followed by CCB and placebo, beta blockers and diuretics in rank order.
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                Author and article information

                Journal
                J Hum Hypertens
                J Hum Hypertens
                Journal of Human Hypertension
                Nature Publishing Group
                0950-9240
                1476-5527
                August 2013
                21 March 2013
                : 27
                : 8
                : 479-486
                Affiliations
                [1 ]Park-Klinikum Bad Krozingen , Bad Krozingen, Germany
                [2 ]ASH Comprehensive Hypertension Center, The University of Chicago Medicine , Chicago, IL, USA
                [3 ]Division of Nephrology, Virginia Commonwealth University Health System , Richmond, VA, USA
                [4 ]Division of Cardiovascular Medicine, SUNY Downstate College of Medicine , Brooklyn, NY, USA
                [5 ]Calhoun Cardiology Center, The University of Connecticut School of Medicine , Farmington, CT, USA
                [6 ]Department of Clinical Science, Takeda Global Research and Development , Deerfield, IL, USA
                [7 ]Department of Statistics, Takeda Global Research and Development , Deerfield, IL, USA
                [8 ]Department of Pharmaceutical Development Division, Takeda Pharmaceuticals International , Deerfield, IL, USA
                Author notes
                [* ]Park-Klinikum Bad Krozingen , Herbert-Hellmann-Allee 44, Bad Krozingen, Baden-Württemberg 79189, Germany. E-mail: g.boenner@ 123456park-klinikum.de
                Article
                jhh20136
                10.1038/jhh.2013.6
                3715765
                23514842
                c0169e62-fcfa-4827-8027-40a4434ac1df
                Copyright © 2013 Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/

                History
                : 20 July 2012
                : 20 December 2012
                : 06 January 2013
                Categories
                Original Article

                Cardiovascular Medicine
                ace inhibitor,angiotensin receptor blocker,azilsartan medoxomil,drug therapy

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