Pharmacological Intervention for Preventing Chemotherapy Induced Cardiomyopathy: A Systematic review, Meta-analysis study and Network Analysis.
Magdy Hanna MD, Usman Mustafa MD, Khagendra Dahal MD, Hussam Watti MD, George Mina MD, Parinita Dherange MD, Pratap Reddy MD, Narendra Duddyala MD and Paari Dominic MD.
The Department of Medicine/Division of Cardiology and Center for Cardiovascular Diseases & Sciences, Louisiana State
University Health Sciences Center- Shreveport (LSUHSC-S), 1501 Kings Hwy, Shreveport, LA 71103, USA
Correspondence:
Paari Dominic MD,
Assistant Professor of Medicine
Div of Cardiology, Dept of Medicine,
LSU Health Sciences Center, Shreveport, LA
Ph: (318) 675 - 5941Fax: (318) 675 – 5686.
E-mail:
Contributions:
Magdy Hanna, Paari Dominic and Usman Mustafa - Design
Magdy Hanna, Paari Dominic and Usman Mustafa- Search & reconciliation
Magdy Hanna, Paari Dominic, Usman Mustafa, Khagendra Dahal, Hussam Watti, Parinita Dherange, George Mina- Data extraction and cross verification
Paari Dominic- Data Analysis and Guarantor
Magdy Hanna, Usman Mustafa and Paari Dominic- Manuscript Preparation
Pratap Reddy, Narendra Duddyala and Paari Dominic- Study supervision and expertise in field.
Anticipated or actual start date: 12/07/2017
Anticipated completion date: 01/12/2018.
Stage of review at time of this submission: completed the preliminary research and started the study selection process.
Named contact: Dr. Magdy Hanna.
Named contact email:
Named contact address: 1501 Kings Highway, Shreveport, LA, 71115.
Named contact phone number: 586-850-8809.
Organization affiliation to review: Louisiana State University Health Science Center, Cardiovascular disease.
Louisiana Clinical and Translational Center (LACATS)
Review team members and their affiliation organization:
Affiliation: LSUHSC
Funding sources/sponsors: The review is supported in part by 2 U54 GM104940-02 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health
Conflict of interest: all participants of the research team have no conflict of interest to declare.
Collaborators: None.
Review questions:
1. 1-Does pharmacological intervention reduce the risk of developing Chemotherapy induced Cardiomyopathy (CCMP)?
2. Does pharmacological intervention preserve Left Ventricular Ejection Fraction (LVEF) in cancer patients treated with anthracyclines?
3. Does pharmacological intervention improve mortality in cancer patients treated with anthracyclines?
4. Are Beta Blockers (BB) more efficacious compared to ACEI?
5. Are BB more efficacious than ARBs?
6. Are BB alone more efficacious than combination of BB and ACEI or ARBs?
7. Are BB more efficacious than Dexrazoxane?
Searches: we will search the following databases PubMed, Biological Abstracts, CINAHL Plus with Full Text, Web of Science,the Cochrane Library and manual search. We will not impose any restriction on language of publication. When available filters/limiters are to be used to limit to clinical studies. All citations will be entered into EndNote Online. Once entered they duplicate citations are manually deleted. Studies published between January 2013 to December, 07, 2017 will be considered.
URL to search strategy:
PubMed Searched on 12/07/2017
https://www.ncbi.nlm.nih.gov/sites/myncbi/julia.esparza.1/collections/53543235/public/
("Antineoplastic Agents"[Mesh] OR "chemotherapy"[All Fields] OR "chemotherapies"[All Fields]) OR ("antineoplastic agents"[Pharmacological Action] OR ("antineoplastic"[All Fields] AND "agents"[All Fields]) OR "antineoplastic agents"[All Fields] OR "antineoplastic"[All Fields]) OR anticarcinogenic[All Fields] OR "anti-carcinogenic"[All Fields] OR "anticarcinogenic agents"[Pharmacological Action] OR "anticarcinogenic agents"[MeSH Terms] OR ("anticarcinogenic"[All Fields] AND "agents"[All Fields]) OR "anticarcinogenic agents"[All Fields] OR "anticarcinogens"[All Fields]
Condition or domain being studied: Cancer Chemotherapy induced Cardiomyopathy.
Participants/Population (Method) of the review:
Inclusion Criteria: Randomized Control (RCTs) and observational trials evaluating pharmacological intervention of CCMP, in both pediatric and adult populations. Studies comparing one pharmacological agent to another or no-treatment/placebo will be included. Studies will be included if they reported incidence of heart failure, change in mean LVEF, cardiotoxicity, cardiac mortality or all-cause mortality, only studies with mean follow up of 6 months or greater will be included.
Exclusion Criteria: studies will be excluded if they: lacked a control arm, had inadequate baseline characteristics, were published only in abstract form, were non-English studies with no English translation or lacked outcomes of interest. Studies will be excluded if they have mean follow up less than 6 months.
Intervention/exposure: Dexrazoxane, BB, ACEI/ARBs, Statins or combination of drugs. Any currently used drug doses will be included. Currently these is no standardized practice for use of prophylactic drugs. In patient or outpatient randomization or initiation of drugs will be included.
Comparators/control: control group included patients with cancer undergoing chemotherapy who did not receive pharmacological intervention and has not been on any potential cardio protective drugs previously. Placebo or another drug (Dexrazoxane, BB, ACEI/ARBs, Statins) as a comparison group will be included. Any currently used drug doses will be included. Currently these is no standardized practice for use of prophylactic drugs. In patient or outpatient randomization or initiation of drugs will be included.
Types of studies to be included: we will include RCTs and observational studies that compared the efficacy of any pharmacological agent with another pharmacological agent or non-treatment/placebo control in preventing CCMP.
Context: Pharmacological prophylaxis for CCMP in adult and pediatric population, their efficacy in reducing the risk of HF, change in mean EF and mortality in in-patient or out-patient settings.
Primary outcomes:
1. Mortality
Secondary outcomes:
1. Risk of developing HF
2. Change in mean EF
Data extraction: titles of the retrieved studies using the search strategy and those which are manually searched will be screened independently by Dr. Magdy Hanna and Dr. Usman Mustafa. The full text of potentially eligible studies will be retrieved and independently assessed for eligibility by Dr. Dahal, Watti and Dherange, any disagreement between them over the eligibility of particular studies will resolved through discussion with a third reviewer, Dr. Dominic. Extracted data will include: study title, design, country, total number of subjects, number of subjects in the study arm and control, type of cancers, type of chemotherapy, mean age, female ratio, previous history of CAD, DM, HTN and HLD. All reported outcomes by all included studies will be extracted.
Risk of bias(quality) assessment: Cochrane Risk of Bias Assessment tool for RCTs will be used. Two review authors will independently assess the risk of bias in included studies by considering the following characteristics:
Randomisation sequence generation: was the allocation sequence adequately generated?
Treatment allocation concealment: was the allocated treatment adequately concealed from study participants and clinicians and other healthcare or research staff at the enrolment stage?
Blinding: were the personnel assessing outcomes and analysing data sufficiently blinded to the intervention allocation throughout the trial?
Completeness of outcome data: were participant exclusions, attrition and incomplete outcome data adequately addressed in the published report?
Selective outcome reporting: is there evidence of selective outcome reporting and might this have affected the study results?
Other sources of bias: was the trial apparently free of any other problems that could produce a high risk of bias? Disagreements between the review authors over the risk of bias in particular studies will be resolved by discussion, with involvement of a third review author where necessary.
Strategy for data synthesis: We will provide a quantitative synthesis of the findings from the included studies. We will provide intervention effects for each study by calculating Odds Ratios (OR) with 95% confidence interval CI. We anticipate that there will be limited scope for meta-analysis because of the range of different outcomes measured across the small number of existing trials. However, where studies have used the same type of intervention and comparator, with the same outcome measure, we will pool the results using a random- effects meta-analysis, with standardized mean differences for continuous outcomes. A network analysis will also be performed to compare the interventions against each other.
Analysis of subgroups: if necessary data available, we will perform subgroup analysis for each drug class. A met-regression analysis will be performed for each intervention and each outcome using Age, sex and baseline LVEF as a modifier if the heterogeneity between studies are significant. (I2>50). Studies testing established cardioprotective drugs (https://www.escardio.org/Education/ESC-Prevention-of-CVD-Programme/Treatment-goals/Cardio-Protective-drugs ) will be grouped together and analyzed separately from novel agents
Type and method of review: Heart failure prevention in cancer patients treated with chemotherapy. Area of interest: Cardiomyopathy/HF in cancer patients treated with chemotherapy.
Language: English.
Country: USA.
Dissemination Plans: A paper will be submitted to a leading journal in this field.
Keywords: Cancer, Cancer chemotherapy, Chemotherapy induced Cardiomyopathy, Cardiomyopathy, Heart Failure, Cancer Mortality, Left Ventricular Ejection Fraction, Cardio-protective drugs.
Current review status: We are in the initial search and screening for potential eligible trails.