Prevalence of unrecognized or “silent” myocardial ischemia in chronic kidney disease patients: Protocol for a systematic review and meta-analysis

Introduction: Chronic kidney disease (CKD) patients are at an extremely high risk of silent myocardial ischemia (SMI). However, there is a dearth of evidence on the worldwide prevalence of this very lethal and yet unrecognizable complication of CKD. The proposed systematic review and meta-analysis aims to estimate the global prevalence of SMI among CKD patients. Methods and analyses: This protocol was conceived according to the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) statement. The systematic review will involve all observational studies and clinical trials published until April 30, 2021, and reporting on the prevalence of SMI in CKD patients. Electronic sources including MEDLINE, Embase, Web of Science, and Cochrane database of systematic reviews will be perused for potentially eligible studies, restricted to only studies published in English or French. Two investigators will independently select studies and use a pre-pilot tested form to extract data. Further, they will independently perform a qualitative assessment of the risk of bias and overall quality of the selected studies, followed by a quantitative assessment using funnel plots and Egger’s tests. The heterogeneity between studies will be assessed with the Cochrane’s Q statistic, and the I2 statistic will measure the percentage of variation across studies that is due to their heterogeneity rather than chance; the I2 will decide if a meta-analysis can be conducted. In case it cannot be conducted, a descriptive analysis will be performed. Otherwise, study-specific estimates will be pooled using either a fixed-effects or a random-effects model, depending on the value of the I2 statistic. Subgroup and random effects meta-regression analyses will further investigate the potential sources of heterogeneity. Finally, sensitivity analyses will be performed to measure the impact of low-quality studies on the results of the meta-analysis, and power calculations will determine the probability that we will detect a true effect if it does exist. PROSPERO registration number: CRD42020211929 Strengths and limitations of this study: The intended systematic review and meta-analysis will fill the knowledge gap on the global prevalence of silent myocardial ischemia (SMI) in CKD patients. The eligible studies will be identified through a methodic literature search followed by a rigorous screening process; we will then use robust meta-analysis tools to pool the data and provide reliable estimates of the global prevalence of SMI in CKD patients. Two major limitations could be: the predominance of clinical trials that might limit the generalizability of the findings, given that some informative patients might have been sidelined by the strict inclusion criteria of these studies; the high probability of type 1 error originating from the important number of subgroup and sensitivity analyses.