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      Renoprotective Effect of the Combination of Renin-angiotensin System Inhibitor and Calcium Channel Blocker in Patients with Hypertension and Chronic Kidney Disease

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          Abstract

          Background:

          Renin-angiotensin system inhibitor and calcium channel blocker (CCB) are widely used in controlling blood pressure (BP) in patients with chronic kidney disease (CKD). We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and CCB (i.e., ACEI/ARB + CCB) with ACEI/ARB monotherapy in patients with hypertension and CKD.

          Methods:

          Publications were identified from PubMed, Embase, Medline, and Cochrane databases. Only randomized controlled trials (RCTs) of BP lowering treatment for patients with hypertension and CKD were considered. The outcomes of end-stage renal disease (ESRD), cardiovascular events, BP, urinary protein measures, estimated glomerular filtration rate (GFR), and adverse events were extracted.

          Results:

          Based on seven RCTs with 628 patients, ACEI/ARB + CCB did not show additional benefit for the incidence of ESRD (risk ratio [ RR] = 0.84; 95% confidence interval [ CI]: 0.52–1.33) and cardiovascular events ( RR = 0.58; 95% CI: 0.21–1.63) significantly, compared with ACEI/ARB monotherapy. There were no significant differences in change from baseline to the end points in diastolic BP (weighted mean difference [WMD] = −1.28 mmHg; 95% CI: −3.18 to −0.62), proteinuria (standard mean difference = −0.55; 95% CI: −1.41 to −0.30), GFR (WMD = −0.32 ml/min; 95% CI: −1.53 to −0.89), and occurrence of adverse events ( RR = 1.05; 95% CI: 0.72–1.53). However, ACEI/ARB + CCB showed a greater reduction in systolic BP (WMD = −4.46 mmHg; 95% CI: −6.95 to −1.97), compared with ACEI/ARB monotherapy.

          Conclusion:

          ACEI/ARB + CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy.

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          Most cited references19

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          Cardiovascular protection and blood pressure reduction: a meta-analysis.

          Whether antihypertensive drugs offer cardiovascular protection beyond blood pressure lowering has not been established. We aimed to investigate whether pharmacological properties of antihypertensive drugs or reduction of systolic pressure accounted for cardiovascular outcome in hypertensive or high-risk patients. In a meta-analysis we extracted summary statistics from published reports, and calculated pooled odds ratios for experimental versus reference treatment. We correlated across-trials odd ratios for differences in systolic pressure between groups. We analysed nine randomised trials comparing treatments in 62605 hypertensive patients. Compared with old drugs (diuretics and b-blockers), calcium-channel blockers and angiotensin converting-enzyme inhibitors offered similar overall cardiovascular protection, but calcium-channel blockers provided more reduction in the risk of stroke (13.5%, 95% CI 1.3-24.2, p=0.03) and less reduction in the risk of myocardial infarction (19.2%, 3.5-37.3, p=0.01). Heterogeneity was significant between trials because of high risk of cardiovascular events on doxazosin in one trial, and high risk of stroke on captopril in another; but systolic pressure differed between groups in these two trials by 2-3 mm Hg. Similar systolic differences occurred in a trial of diltiazem versus old drugs, and in three trials of converting-enzyme inhibitor against placebo in high-risk patients. Meta-regression across 27 trials (136124 patients) showed that odds ratios could be explained by achieved differences in systolic pressure. Our findings emphasise that blood pressure control is important. All antihypertensive drugs have similar long-term efficacy and safety. Calcium-channel blockers might be especially effective in stroke prevention. We did not find that converting-enzyme inhibitors or a-blockers affect cardiovascular prognosis beyond their antihypertensive effects.
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            Cochrane Handbook for systematic reviews of interventions version 5.1.0

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              Proteinuria as a risk factor for cardiovascular disease and mortality in older people: a prospective study.

              The prognostic significance of proteinuria in older people is not well defined. We examined the associations between proteinuria and incident coronary heart disease, cardiovascular mortality, and all-cause mortality in older people. Casual dipstick proteinuria was determined in 1,045 men (mean [+/- SD] age 68 +/- 7 years) and 1,541 women (mean age 69 +/- 7 years) attending the 15th biennial examination of the Framingham Heart Study. Participants were divided by grade of proteinuria: none (85.3%), trace (10.2%), and greater-than-trace (4.5%). Cox proportional hazards analyses were used to determine the relations of baseline proteinuria to the specified outcomes, adjusting for other risk factors, including serum creatinine level. During 17 years of follow-up, there were 455 coronary heart disease events, 412 cardiovascular disease deaths, and 1,214 deaths. In men, baseline proteinuria was associated with all-cause mortality (hazards ratio [HR] = 1.3, 95% confidence interval [CI] 1.0 to 1.7 for trace proteinuria; HR = 1.3, 95% CI 1.0 to 1.8 for greater-than-trace proteinuria; P for trend = 0.02). In women, trace proteinuria was associated with cardiovascular disease death (HR = 1. 6, 95% CI 1.1 to 2.4), and all-cause mortality (HR = 1.4, 95% CI 1.1 to 1.7). Proteinuria is a significant, although relatively weak, risk factor for all-cause mortality in men and women, and for cardiovascular disease mortality in women.
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                Author and article information

                Journal
                Chin Med J (Engl)
                Chin. Med. J
                CMJ
                Chinese Medical Journal
                Medknow Publications & Media Pvt Ltd (India )
                0366-6999
                05 March 2016
                : 129
                : 5
                : 562-569
                Affiliations
                [1 ]Department of Internal Medicine, Renal Division, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
                [2 ]West China Biostatistics and Cost-Benefit Analysis Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
                [3 ]Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA
                Author notes
                Address for correspondence: Dr. Ping Fu, Department of Internal Medicine, Renal Division, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China E-Mail: fupinghx@ 123456163.com
                Article
                CMJ-129-562
                10.4103/0366-6999.176987
                4804438
                26904991
                25208ce0-d6f4-4654-99f3-22148264ceef
                Copyright: © 2016 Chinese Medical Journal

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 20 October 2015
                Categories
                Meta Analysis

                calcium channel blocker,chronic kidney disease,hypertension,renin-angiotensin system inhibitor,renoprotection,therapy

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