Statins in patients with peripheral artery disease: A protocol for a systematic review and network meta-analysis

Introduction: Patients with peripheral artery disease (PAD) have been found to suffer from diabetes, obesity, lipid abnormalities, including elevated levels of total and LDL-cholesterol as well as triglyceride levels. Therefore, the objective of the current study is to conduct a systematic review with network meta-analysis to compare the effects of statins classes on PAD patients for future major adverse cardiovascular events. Methods and analysis: We will search the PubMed, EMBASE, Cochrane Library, Web of Science, Embase, google scholar, clinical trials registry (ClinicalTrials. gov) for unpublished or undergoing research listed in registry platforms. Randomized clinical trials (RCTs) studies published in English up to 31 January 2018, and which include direct and/or indirect evidence, will be included. Studies will be retrieved by searching four electronic databases and cross-referencing. Dual selection and abstraction of data will occur. The primary outcome will all-cause mortality, new event of acute myocardial infarction, stroke (hemorrhagic and ischemic), hospitalization for acute coronary syndrome and urgent revascularization procedures and cardiovascular mortality. Secondary outcomes will be assessment of the differences in change of total cholesterol (TC), low-density lipoprotein (LDL-C), apolipoprotein B (ApoB), high density lipoprotein (HDL-C), changes in pain free walking distance (PFWD) and quality of life (QOL). Risk of bias will be assessed using the Cochrane Risk of Bias assessment instrument for RCTs. Network meta-analysis will be performed using multivariate random-effects meta-regression models. The surface under the cumulative ranking curve will be used to provide a hierarchy of statins that reduce cardiovascular mortality in PAD patients. A revised version of the Cochrane Risk of Bias tool (RoB 2.0) will be used to assess the risk of bias in eligible RCTs. Subgroup and sensitivity analysis will also be performed. Ethics and dissemination: The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. PROSPERO registration number: CRD42018082024 *Correspondence to: Leonardo Roever, Department of Clinical Research, Federal University of Uberlândia, Brazil, E-mail: leonardoroever@hotmail.com