CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 2, May – August 2024 116 AFRICA be beneficial.5 Warfarin anticoagulation might be associated with increased calcification of atherosclerotic plaques.6 Phosphate binders and bisphosphonates, which are applied for prevention and treatment of osteoporosis, have not been observed to have a constant effect on the progression of arterial calcification.7,8 Studies are necessary to develop therapeutic strategies and decrease atherosclerotic disease burden. CT measuring coronary artery calcification, plain lateral abdominal X-ray or abdominal artery calcification scores can be measured to assess vascular calcification. These parameters are strongly related to the degree of atherosclerosis, the progression of coronary heart disease and long-term mortality independent of traditional risk factors,9 and the application of coronary artery calcification scores or abdominal aortic calcification scores may improve cardiovascular risk prediction in asymptomatic patients.10 Pulse-wave velocity (PWV) is the gold-standard approach for estimating arterial stiffness.11 Increased PWV can be adopted to predict cardiovascular complications and mortality in dialysis patients.12 To diminish the destructive effects of spiral aortic stiffness in end-stage renal disease patients, several interventions have been developed, and PWV has been used to observe the responses. Over the years, up-to-date clinical studies targeting the cellular mechanisms of calcification have offered promising guidelines for drug development. However, vascular calcification is not expected to be reduced by any mechanism once there is deposit in the apoptic vascular cell due to inflammation and upregulation of osteogenic programme. It only can be halted or slowed down.13 At present, the available treatment choices to slow down vascular calcification in dialysis patients include adequate dialytic therapy, use of non-calcium-containing phosphate binders and calcimimetic agents, active vitamin D, myoinositol hexaphosphate, denosumab, tissue non-specific alkaline phosphatase inhibitors, bisphosphonates and vitamin K.14,15 Another promising approach is the use of sodium thiosulfate (STS), a chelating agent that is commonly used to prevent cyanide poisoning.16 In recent years, off-label treatment with STS has been increasingly used for the treatment of soft tissue calcifications in calcific uraemic arteriolopathy or calciphylaxis.17 Studies have also found that STS might delay the development of vascular calcification in dialysis individuals.18-35 Therefore, to guide clinical practice and shed light on vascular calcification, we performed a systematic review to evaluate the safety and efficacy of intravenous STS treatment on vascular calcification, as measured by the coronary artery calcification (CACS) score or abdominal aorta calcification score (AACS), PWV, and the chronic kidney disease–mineral bone disease index. Methods We performed this meta-analysis in accordance with the PRISMA guidelines.36 This protocol was registered on the INPLASY website (registration number: INPLASY202230018). This systematic review was in accordance with the World Medical Association Declaration of Helsinki. The search strategy was launched and executed by two authors (YHS and GYC) independently. We searched the Web of Science, Embase, Cochrane Library, Wanfang, CNKI, China Biology Medicine disc and Weipu databases up to 9 March 2022, for studies to synthesise findings on the efficacy and safety of STS in the progression of vascular calcification in dialysis patients. The following search themes were used in various combinations: sodium thiosulphate, sodium thiosulfate, sodium hydrosulfite, dialysis and vascular calcification. We also scanned the reference lists of relevant included studies to identify potential eligible articles. Based on the following inclusion criteria, two independent authors illustrated the item of studies produced by the search. Any disagreement was settled by consensus between the reviewers or proclamation with a third party (TP). The titles and abstracts of all studies were screened, and then two authors reviewed the full texts of the relevant articles. The inclusion criteria were as follows: (1) randomised, controlled trials (RCTs) or studies that included patients presenting with vascular calcification treated with and without STS to provide a comparison between intervention and control groups; (2) studies that analysed the effect of intravenous STS on the CACS or AACS or plain lateral abdominal X-ray of adults on dialysis (age over 18 years). PWV was considered an appropriate measure of arterial stiffness. There were no restrictions regarding sample size or research duration. The exclusion criteria were case reports, review articles, letters, unpublished studies, or studies that were not conducted on clinical patients. Quality assessment of each study was independently analysed by YHS and GYC. We used the Cochrane risk-of-bias tool to evaluate RCTs and the risk of bias in non-randomised studies of interventions to evaluate non-RCTs.37,38 Two reviewers would respectively evaluate each trial with ‘low’, ‘unclear’ or ‘high’ risk of bias. A trial was considered at high risk of bias if one or more domains were evaluated to be high risk. A trial would be regarded as low risk of bias if all domains were judged to be low risk. Otherwise, it would be considered at unclear risk of bias. Disagreements in the scores were resolved by team discussion. We extracted common characteristics of each study, including the first author’s name, issuing time, nation, sample size, dose and duration of STS, main outcomes and adverse events. These data are provided in Table 1. We determined the mean difference and standard deviation (SD) of vascular calcification results from the STS treatment and control groups. If the mean change and SD were not provided in the study, we calculated these parameters using the median, interquartile range (IQR) and sample size.39 The primary outcome of the study was absolute changes in CACS or AACS determined using CT measuring coronary artery calcification, plain lateral abdominal X-ray, or abdominal aorta calcification. The secondary endpoint was the absolute changes in PWV levels from baseline to the end of treatment. Safety data included adverse events and changes in serum highsensitivity C-reactive protein (hsCRP), parathyroid hormone (iPTH), calcium, phosphate and bicarbonate levels monitored after treatment. Statistical analysis Statistical meta-analysis of the included studies was performed by Review Manager version 5. Due to the differences in evaluation methods and sections, we measured the standard
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