Effects of calcium channel blockers comparing to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with hypertension and chronic kidney disease stage 3 to 5 and dialysis: A systematic review and meta-analysis

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Abstract

Background

Calcium channel blocker (CCB) or two renin angiotensin aldosterone system blockades (RAAS), angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are major potent and prevalently used as initial antihypertensive agents for mild to moderate hypertension, but no uniform agreement as to which antihypertensive drugs should be given for initial therapy, especially among chronic kidney disease (CKD) patients.

Design

A systematic review and meta-analysis comparing CCBs and the two RAAS blockades for hypertensive patients with CKD stage 3 to 5D. The inclusion criteria for this systematic review was RCT that compared the effects of CCBs and the two RAAS blockades in patients with hypertension and CKD. The exclusion criteria were (1) renal transplantation, (2) CKD stage 1 or 2, (3) combined therapy (data cannot be extracted separately). Outcomes were blood pressure change, mortality, heart failure, stroke or cerebrovascular events, and renal outcomes.

Results

21 randomized controlled trials randomized 9,492 patients with hypertensive and CKD into CCBs and the two RAAS blockades treatments. The evidence showed no significant differences in blood presser change, mortality, heart failure, stroke or cerebrovascular events, and renal outcomes between CCBs group and the two RAAS blockades group. The publication bias of pooled mean blood presser change that was detected by Egger’s test was non-significant.

Conclusions

CCBs has similar effects on long term blood pressure, mortality, heart failure, stroke or cerebrovascular events, and renal function to RAAS blockades in patients CKD stage 3 to 5D and hypertension.

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Most cited references 43

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Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial.

Jackson T Wright, George C. Bakris, Tom Greene … (2002)

Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD. To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension. Randomized 3 x 2 factorial trial with enrollment from February 1995 to September 1998. A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years. Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n = 554) or 92 mm Hg or less (lower; n = 540), and to initial treatment with either a beta-blocker (metoprolol 50-200 mg/d; n = 441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n = 436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n = 217). Open-label agents were added to achieve the assigned BP goals. Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or > or =25 mL/min per 1.73 m2) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol. Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m2 per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 m2 per year; P =.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group = 2%; 95% confidence interval [CI], -22% to 21%; P =.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38%; P =.04) and 38% (95% CI, 14%-56%; P =.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups. No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline.

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Issues in the selection of a summary statistic for meta-analysis of clinical trials with binary outcomes.

Michael J. Deeks (2002)

Meta-analysis of binary data involves the computation of a weighted average of summary statistics calculated for each trial. The selection of the appropriate summary statistic is a subject of debate due to conflicts in the relative importance of mathematical properties and the ability to intuitively interpret results. This paper explores the process of identifying a summary statistic most likely to be consistent across trials when there is variation in control group event rates. Four summary statistics are considered: odds ratios (OR); risk differences (RD) and risk ratios of beneficial (RR(B)); and harmful outcomes (RR(H)). Each summary statistic corresponds to a different pattern of predicted absolute benefit of treatment with variation in baseline risk, the greatest difference in patterns of prediction being between RR(B) and RR(H). Selection of a summary statistic solely based on identification of the best-fitting model by comparing tests of heterogeneity is problematic, principally due to low numbers of trials. It is proposed that choice of a summary statistic should be guided by both empirical evidence and clinically informed debate as to which model is likely to be closest to the expected pattern of treatment benefit across baseline risks. Empirical investigations comparing the four summary statistics on a sample of 551 systematic reviews provide evidence that the RR and OR models are on average more consistent than RD, there being no difference on average between RR and OR. From a second sample of 114 meta-analyses evidence indicates that for interventions aimed at preventing an undesirable event, greatest absolute benefits are observed in trials with the highest baseline event rates, corresponding to the model of constant RR(H). The appropriate selection for a particular meta-analysis may depend on understanding reasons for variation in control group event rates; in some situations uncertainty about the choice of summary statistic will remain. Copyright 2002 John Wiley & Sons, Ltd.

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Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial.

Gregor Brown, Don Cleveland, Robert Toto … (2001)

Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans. To compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine), and a beta-blocker (metoprolol) on hypertensive renal disease progression. Interim analysis of a randomized, double-blind, 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease (glomerular filtration rate [GFR] of 20-65 mL/min per 1.73 m(2)) enrolled between February 1995 and September 1998. This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000. Participants were randomly assigned to receive amlodipine, 5 to 10 mg/d (n = 217), ramipril, 2.5 to 10 mg/d (n = 436), or metoprolol, 50 to 200 mg/d (n = 441), with other agents added to achieve 1 of 2 blood pressure goals. The primary outcome measure was the rate of change in GFR; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50% or 25 mL/min per 1.73 m(2), end-stage renal disease, or death. Among participants with a urinary protein to creatinine ratio of >0.22 (corresponding approximately to proteinuria of more than 300 mg/d), the ramipril group had a 36% (2.02 [SE, 0.74] mL/min per 1.73 m(2)/y) slower mean decline in GFR over 3 years (P =.006) and a 48% reduced risk of the clinical end points vs the amlodipine group (95% confidence interval [CI], 20%-66%). In the entire cohort, there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups (P =.38). However, compared with the amlodipine group, after adjustment for baseline covariates the ramipril group had a 38% reduced risk of clinical end points (95% CI, 13%-56%), a 36% slower mean decline in GFR after 3 months (P =.002), and less proteinuria (P<.001). Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria.

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Author and article information

Contributors

Yen-Chung Lin: Role: Formal analysisRole: Funding acquisitionRole: SupervisionRole: Writing – original draftRole: Writing – review & editing

Jheng-Wei Lin: Role: Data curationRole: Formal analysisRole: ValidationRole: Writing – original draft

Mai-Szu Wu: Role: ValidationRole: Writing – review & editing

Kuan-Chou Chen: Role: Supervision

Chiung-Chi Peng: Role: Supervision

Yi-No Kang:

ORCID: http://orcid.org/0000-0001-8244-2846

Role: ConceptualizationRole: MethodologyRole: SoftwareRole: Writing – review & editing

Tatsuo Shimosawa: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 14 December 2017

Publication date Collection: 2017

Volume: 12

Issue: 12

Electronic Location Identifier: e0188975

Affiliations

[1 ] Center for Evidence-based Medicine, Department of Education, Taipei Medical University Hospital, Taipei, Taiwan, R.O.C

[2 ] Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C

[3 ] Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, R.O.C

[4 ] Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C

The University of Tokyo, JAPAN

Author notes

Competing Interests: The authors have declared that no competing interests exist.

* E-mail: academicnono@ 123456gmail.com (YNK); b101100072@ 123456tmu.edu.tw (JWL)

Author information

Yi-No Kang http://orcid.org/0000-0001-8244-2846

Article

Publisher ID: PONE-D-17-31667

DOI: 10.1371/journal.pone.0188975

PMC ID: 5730188

PubMed ID: 29240784

SO-VID: af442e97-1239-4215-82ec-02b056a9d733

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 3 September 2017

Date accepted : 16 November 2017

Page count

Figures: 4, Tables: 3, Pages: 18

Funding

Funded by: funder-id http://dx.doi.org/10.13039/501100004700, Taipei Medical University;

Award ID: 106TMU-TMUH-23

Award Recipient : Yen-Chung Lin

This research received a grant from Taipei Medical University 106TMU-TMUH-23 ( http://219.87.146.141/rd/htdocs/modules/tadnews/index.php?nsn=246). The first author Yen-Chung Lin M.D. received the grant, and initiated this study. He wrote the first draft.

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Data Availability The present systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines ( S1 Table). This study was registered in PROSPERO with registration number CRD42017069375. Data are from the 21 randomized controlled trials whose authors' contact information can be found in the Supporting Information file " S2 File."

Effects of calcium channel blockers comparing to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with hypertension and chronic kidney disease stage 3 to 5 and dialysis: A systematic review and meta-analysis

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Most cited references 43

Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial.

Issues in the selection of a summary statistic for meta-analysis of clinical trials with binary outcomes.

Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial.

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