Accepted Manuscript Percutaneous Revascularization for Atherosclerotic Renal Artery Stenosis: A MetaAnalysis of Randomized Controlled Trials Yuefeng Zhu, MD, Jun Ren, PhD, Xiaobo Ma, MD, Mu-Hsun Chen, Yifan Zhou, PhD, Mingjuan Jin, PhD, Zhenjie Liu, MD, PhD PII:
S0890-5096(15)00568-3
DOI:
10.1016/j.avsg.2015.06.062
Reference:
AVSG 2457
To appear in:
Annals of Vascular Surgery
Received Date: 14 March 2015 Revised Date:
30 May 2015
Accepted Date: 21 June 2015
Please cite this article as: Zhu Y, Ren J, Ma X, Chen MH, Zhou Y, Jin M, Liu Z, Percutaneous Revascularization for Atherosclerotic Renal Artery Stenosis: A Meta-Analysis of Randomized Controlled Trials, Annals of Vascular Surgery (2015), doi: 10.1016/j.avsg.2015.06.062. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
ORIGINAL ARTICLE Percutaneous Revascularization for Atherosclerotic Renal Artery Stenosis: A Meta-Analysis of Randomized Controlled Trials
RI PT
Yuefeng Zhu1 MD, Jun Ren2 PhD, Xiaobo Ma2 MD, Mu-Hsun Chen2, Yifan Zhou2 PhD, Mingjuan Jin3 PhD, Zhenjie Liu4 MD, PhD. 1
Department of Vascular Surgery, Sir Run Run Shaw Hospital, Zhejiang University,
2
SC
Hangzhou, China (Y Zhu);
Department of Vascular Surgery, WIMR, University of Wisconsin-Madison, WI, USA (J
Ren, X Ma, MH Chen, Y Zhou);
Department of Biostatistics, Zhejiang University, Hangzhou, China (M Jin)
4
Department of Vascular Surgery, The Second Affiliated Hospital of Zhejiang University
M AN U
3
School of Medicine, Hangzhou, China (Z Liu)
EP
Correspondence to:
TE D
Running Head: PR vs. Medication alone for atherosclerotic RAS
Zhenjie Liu, M.D., Ph.D.
Department of Vascular Surgery,
AC C
2nd Affiliated Hospital School of Medicine, Zhejiang University,
Jiefang Road 88, Hangzhou, China. Tel: +86-571-89713709 (office) Email: [email protected]
ACCEPTED MANUSCRIPT Abstract Background PR of atherosclerotic RAS improves patency in the renovascular disease. However, whether PR is associated with additional clinical benefit in the patients with
RI PT
atherosclerotic RAS remains controversial. Objective We conducted a meta-analysis to evaluate the outcomes of PR versus medication alone for atherosclerotic RAS.
SC
Methods We compiled an electronic database of prospective, randomized, controlled trials
M AN U
related to the efficacy of PR versus medication for RAS. The standardized mean difference (SMD) or relative risk ratios (RRs) were estimated with 95% confidence intervals (CI) based on an intention-to-treat analysis. We considered the following outcomes: changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), reduction of
TE D
anti-hypertension medication, serum creatinine (SCr), worsening renal failure, mortality, stroke, and congestive heart failure.
Results Seven trials with a total of 1,916 patients (937 with PR, 979 with medication
EP
alone) were analyzed. The changes in SBP/DBP from baseline were similar between the
AC C
two groups (Changes in SBP: p=0.69; Changes in DBP: p=0.15). PR treatment led to a statistically significant decrease in the number of anti-hypertensive medications compared medical management alone (SMD -0.18, 95%CI -0.27 to -0.10, p6.8% of patients over the age of 65
SC
years. 3-6 Despite the frequency of RAS, there is no consensus on the diagnosis or therapy.7
M AN U
Although atherosclerotic RAS is commonly associated with hypertension and renal insufficiency, the frequency of hypertension resulting from RAS is unknown.3, 8
Percutaneous revascularization (PR) has gradually replaced surgical revascularization in
TE D
the patients with RAS over the past decade years,9, 10 and remains the dominant procedural option for the treatment of atherosclerotic RAS.11 However, unlike the effectiveness of treating fibromuscular dysplasia by percutaneous transluminal angioplasty (PTA), the
EP
optimal management of atherosclerotic RAS remains controversial.1, 12 Ambiguous clinical
AC C
observations and disappointing results from prospective randomized controlled trials (RCTs) have not helped clarify the clinical treatment of atherosclerotic RAS.13, 14 As a result, the guidelines for directly treating atherosclerotic RAS contain no Class I recommendations. 15
Recently, one large, randomized, controlled trial comparing the efficacy and safety of PR plus medication and medical treatment alone was published: the Cardiovascular Outcomes
ACCEPTED MANUSCRIPT in Renal Atherosclerotic Lesions (CORAL) study.7 CORAL, sponsored by the National Institute of Health, enrolled more than 900 patients with atherosclerotic RAS to compare PR with medication alone in terms of efficacy, complications, and safety.7, 16 This trial
RI PT
enhanced our knowledge of the comparative outcomes of PR plus medication and medical management alone. Thus, we performed an updated systematic review and meta-analysis to
Data Sources and Search Strategy
M AN U
Methods
SC
include this new randomized controlled trial.
The systematic review and meta-analysis was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement 17. We
TE D
performed a literature search of MEDLINE via PubMed (1990 to present), Ovid’s database (1995 to present), Cochrane Controlled Trials Register databases, ISI Web of Science (1990 to present), Google Scholar (1990 to present), and the Chinese Wanfang
EP
database (1995 to present). MEDLINE (http://www.ncbi.nlm.nih.gov/pubmed) was
AC C
searched using both Mesh terms and text words: 1) “angioplasty”, or “balloon”, “percutaneous
transluminal
angioplasty”,
“stent”,
or
“revascularization”;
2)
“renovascular”, “renal artery obstruction” or “stenosis”; 3) “hypertension” or “chronic renal insufficiency, CRI”; and 4) “randomized controlled trial”, “controlled study”, “random allocation”, “controlled clinical trials”, “control groups”, “clinical trial”, or “clinical study”. References from identified studies were also reviewed to ensure that all pertinent published papers had been identified.
ACCEPTED MANUSCRIPT
Inclusion / Exclusion Criteria
RI PT
Inclusion/exclusion criteria were described in Table 1.
Studys selection and Data Extraction
We enrolled RCTs that compared percutaneous revascularization and medical management
SC
alone in patients with atherosclerotic RAS. First, three investigators independently
M AN U
reviewed the titles and abstracts of all citations to identify eligible studies and to exclude duplicates. Secondly, they reviewed the corresponding publications in full text to assess if the studies met the inclusion criteria. The final inclusion of studies was based on agreement among the investigators. Two investigators used a standardized form to extract
TE D
the data from each study that assessed the study type, patient inclusion and exclusion criteria, percutaneous revascularization technique, changes in SBP/DBP, reduction of anti-hypertension medication, serum creatinine (SCr), worsen renal failure, mortality,
AC C
EP
stroke, and congestive heart failure.
Assessment of Methodologic Quality The quality of the trials was assessed using the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2. Each included trial was assessed independently for the following methodological qualities: sequence generation, allocation, concealment, participant blinding, incomplete outcome data, selective outcome reporting, baseline imbalance bias, early stopping bias, academic bias, differential expertise bias, and sources
ACCEPTED MANUSCRIPT of funding bias. Trials which did not report the outcomes of completely randomized patients were considered as suffering from bias owing to incomplete outcome data, and therefore were excluded from further analysis. To assess the effect of trial quality on the
Assessment of risk of bias in included studies
RI PT
size of the observed effect, we performed sensitivity analyses.
SC
Included studies were systematically evaluated for their quality using instructions
M AN U
described in the Cochrane Handbook for Systematic Reviews of Interventions. 18 The items used for the assessment of each study were adequacy of sequence generation, allocation concealment, blinding, incomplete outcome reporting, and other potential sources of bias. According to the recommendations of the Cochrane Handbook, a judgment of ‘+’ was
TE D
indicative of low risk of bias, while ‘-’ indicated high risk of bias. Labeling as ‘?’ indicated unclear or unknown risk of bias. All cross sectional studies were considered comparable in
EP
quality and the same was for controlled trials.
AC C
Data Synthesis and Analysis
Two investigators independently carried out the analyses using the meta-analysis statistical software Review Manager Version 5.1 (The Cochrane Collaboration, 2011, The Nordic Cochrane Centre, Copenhagen, Denmark). Both random-effects and fixed-effects meta-analytical models were used to calculate the pooled relative risks (RRs) and 95% confidence intervals (CIs) for percutaneous revascularization compared with medical management alone. The choice of a fixed-effects model and a random-effects model was
ACCEPTED MANUSCRIPT secondary to the examination of the factors that contributed to heterogeneity. Probability (p) values
S0890-5096(15)00568-3
DOI:
10.1016/j.avsg.2015.06.062
Reference:
AVSG 2457
To appear in:
Annals of Vascular Surgery
Received Date: 14 March 2015 Revised Date:
30 May 2015
Accepted Date: 21 June 2015
Please cite this article as: Zhu Y, Ren J, Ma X, Chen MH, Zhou Y, Jin M, Liu Z, Percutaneous Revascularization for Atherosclerotic Renal Artery Stenosis: A Meta-Analysis of Randomized Controlled Trials, Annals of Vascular Surgery (2015), doi: 10.1016/j.avsg.2015.06.062. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
ORIGINAL ARTICLE Percutaneous Revascularization for Atherosclerotic Renal Artery Stenosis: A Meta-Analysis of Randomized Controlled Trials
RI PT
Yuefeng Zhu1 MD, Jun Ren2 PhD, Xiaobo Ma2 MD, Mu-Hsun Chen2, Yifan Zhou2 PhD, Mingjuan Jin3 PhD, Zhenjie Liu4 MD, PhD. 1
Department of Vascular Surgery, Sir Run Run Shaw Hospital, Zhejiang University,
2
SC
Hangzhou, China (Y Zhu);
Department of Vascular Surgery, WIMR, University of Wisconsin-Madison, WI, USA (J
Ren, X Ma, MH Chen, Y Zhou);
Department of Biostatistics, Zhejiang University, Hangzhou, China (M Jin)
4
Department of Vascular Surgery, The Second Affiliated Hospital of Zhejiang University
M AN U
3
School of Medicine, Hangzhou, China (Z Liu)
EP
Correspondence to:
TE D
Running Head: PR vs. Medication alone for atherosclerotic RAS
Zhenjie Liu, M.D., Ph.D.
Department of Vascular Surgery,
AC C
2nd Affiliated Hospital School of Medicine, Zhejiang University,
Jiefang Road 88, Hangzhou, China. Tel: +86-571-89713709 (office) Email: [email protected]
ACCEPTED MANUSCRIPT Abstract Background PR of atherosclerotic RAS improves patency in the renovascular disease. However, whether PR is associated with additional clinical benefit in the patients with
RI PT
atherosclerotic RAS remains controversial. Objective We conducted a meta-analysis to evaluate the outcomes of PR versus medication alone for atherosclerotic RAS.
SC
Methods We compiled an electronic database of prospective, randomized, controlled trials
M AN U
related to the efficacy of PR versus medication for RAS. The standardized mean difference (SMD) or relative risk ratios (RRs) were estimated with 95% confidence intervals (CI) based on an intention-to-treat analysis. We considered the following outcomes: changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), reduction of
TE D
anti-hypertension medication, serum creatinine (SCr), worsening renal failure, mortality, stroke, and congestive heart failure.
Results Seven trials with a total of 1,916 patients (937 with PR, 979 with medication
EP
alone) were analyzed. The changes in SBP/DBP from baseline were similar between the
AC C
two groups (Changes in SBP: p=0.69; Changes in DBP: p=0.15). PR treatment led to a statistically significant decrease in the number of anti-hypertensive medications compared medical management alone (SMD -0.18, 95%CI -0.27 to -0.10, p6.8% of patients over the age of 65
SC
years. 3-6 Despite the frequency of RAS, there is no consensus on the diagnosis or therapy.7
M AN U
Although atherosclerotic RAS is commonly associated with hypertension and renal insufficiency, the frequency of hypertension resulting from RAS is unknown.3, 8
Percutaneous revascularization (PR) has gradually replaced surgical revascularization in
TE D
the patients with RAS over the past decade years,9, 10 and remains the dominant procedural option for the treatment of atherosclerotic RAS.11 However, unlike the effectiveness of treating fibromuscular dysplasia by percutaneous transluminal angioplasty (PTA), the
EP
optimal management of atherosclerotic RAS remains controversial.1, 12 Ambiguous clinical
AC C
observations and disappointing results from prospective randomized controlled trials (RCTs) have not helped clarify the clinical treatment of atherosclerotic RAS.13, 14 As a result, the guidelines for directly treating atherosclerotic RAS contain no Class I recommendations. 15
Recently, one large, randomized, controlled trial comparing the efficacy and safety of PR plus medication and medical treatment alone was published: the Cardiovascular Outcomes
ACCEPTED MANUSCRIPT in Renal Atherosclerotic Lesions (CORAL) study.7 CORAL, sponsored by the National Institute of Health, enrolled more than 900 patients with atherosclerotic RAS to compare PR with medication alone in terms of efficacy, complications, and safety.7, 16 This trial
RI PT
enhanced our knowledge of the comparative outcomes of PR plus medication and medical management alone. Thus, we performed an updated systematic review and meta-analysis to
Data Sources and Search Strategy
M AN U
Methods
SC
include this new randomized controlled trial.
The systematic review and meta-analysis was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement 17. We
TE D
performed a literature search of MEDLINE via PubMed (1990 to present), Ovid’s database (1995 to present), Cochrane Controlled Trials Register databases, ISI Web of Science (1990 to present), Google Scholar (1990 to present), and the Chinese Wanfang
EP
database (1995 to present). MEDLINE (http://www.ncbi.nlm.nih.gov/pubmed) was
AC C
searched using both Mesh terms and text words: 1) “angioplasty”, or “balloon”, “percutaneous
transluminal
angioplasty”,
“stent”,
or
“revascularization”;
2)
“renovascular”, “renal artery obstruction” or “stenosis”; 3) “hypertension” or “chronic renal insufficiency, CRI”; and 4) “randomized controlled trial”, “controlled study”, “random allocation”, “controlled clinical trials”, “control groups”, “clinical trial”, or “clinical study”. References from identified studies were also reviewed to ensure that all pertinent published papers had been identified.
ACCEPTED MANUSCRIPT
Inclusion / Exclusion Criteria
RI PT
Inclusion/exclusion criteria were described in Table 1.
Studys selection and Data Extraction
We enrolled RCTs that compared percutaneous revascularization and medical management
SC
alone in patients with atherosclerotic RAS. First, three investigators independently
M AN U
reviewed the titles and abstracts of all citations to identify eligible studies and to exclude duplicates. Secondly, they reviewed the corresponding publications in full text to assess if the studies met the inclusion criteria. The final inclusion of studies was based on agreement among the investigators. Two investigators used a standardized form to extract
TE D
the data from each study that assessed the study type, patient inclusion and exclusion criteria, percutaneous revascularization technique, changes in SBP/DBP, reduction of anti-hypertension medication, serum creatinine (SCr), worsen renal failure, mortality,
AC C
EP
stroke, and congestive heart failure.
Assessment of Methodologic Quality The quality of the trials was assessed using the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2. Each included trial was assessed independently for the following methodological qualities: sequence generation, allocation, concealment, participant blinding, incomplete outcome data, selective outcome reporting, baseline imbalance bias, early stopping bias, academic bias, differential expertise bias, and sources
ACCEPTED MANUSCRIPT of funding bias. Trials which did not report the outcomes of completely randomized patients were considered as suffering from bias owing to incomplete outcome data, and therefore were excluded from further analysis. To assess the effect of trial quality on the
Assessment of risk of bias in included studies
RI PT
size of the observed effect, we performed sensitivity analyses.
SC
Included studies were systematically evaluated for their quality using instructions
M AN U
described in the Cochrane Handbook for Systematic Reviews of Interventions. 18 The items used for the assessment of each study were adequacy of sequence generation, allocation concealment, blinding, incomplete outcome reporting, and other potential sources of bias. According to the recommendations of the Cochrane Handbook, a judgment of ‘+’ was
TE D
indicative of low risk of bias, while ‘-’ indicated high risk of bias. Labeling as ‘?’ indicated unclear or unknown risk of bias. All cross sectional studies were considered comparable in
EP
quality and the same was for controlled trials.
AC C
Data Synthesis and Analysis
Two investigators independently carried out the analyses using the meta-analysis statistical software Review Manager Version 5.1 (The Cochrane Collaboration, 2011, The Nordic Cochrane Centre, Copenhagen, Denmark). Both random-effects and fixed-effects meta-analytical models were used to calculate the pooled relative risks (RRs) and 95% confidence intervals (CIs) for percutaneous revascularization compared with medical management alone. The choice of a fixed-effects model and a random-effects model was
ACCEPTED MANUSCRIPT secondary to the examination of the factors that contributed to heterogeneity. Probability (p) values
