Sirolimus-Coated versus Paclitaxel-Coated Balloons for Coronary Artery Disease: A Grade Assessed Systematic Review and Meta-Analysis.

Although use of sirolimus-based analogs has shown superiority over paclitaxel in drug-eluting stents, the relative efficacy of these two agents released from drug-coated balloons (DCB) is unclear. The present meta-analysis is aimed to compare outcomes after percutaneous coronary intervention (PCI) with paclitaxel-coated balloons (PCB) versus sirolimus-coated balloons (SCB) for either in-stent restenosis or native de novo lesions. The study outcomes were 1) target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, or target lesion revascularization, and 2) follow-up angiographic parameters including late lumen loss (LLL), diameter stenosis, and minimal lumen diameter (MLD). Pooled odds ratios (OR) and weighted mean differences (WMD) with 95% confidence intervals (CI) were calculated by using random-effects models. A search of PubMed, EMBASE, and Cochrane Library from their inception to January 2024 identified five randomized clinical trials and three observational studies with a total of 1861 patients (889 in PCB and 972 in SCB groups). During 9-12 months of follow-up, there was no significant difference in TLF (OR 1.01, 95% CI 0.75-1.35) between the two groups. On follow-up angiography at 6-9 months, MLD (WMD 0.10, 95% CI 0.02-0.17) was larger in PCB but there was no statistically significant difference in LLL (WMD -0.11, 95% CI -0.23-0.02) and diameter stenosis (WMD -3.33, 95% CI -8.11-1.45). Among patients undergoing DCB-only PCI, the risk of TLF was similar during 9-12 months of follow-up after PCB and SCB treatment. However, the MLD was larger favoring PCB over SCB on follow-up angiography.

Introduction: Coronary in-stent restenosis (ISR) remains challenging despite stent technology advancements. Paclitaxel-coated balloons (PCB) offer a promising non-implant approach to deliver antiproliferative agents directly to the vessel wall. This meta-analysis aims to evaluate the comparative effectiveness of PCB versus uncoated balloons (UCB) in managing coronary ISR to address emerging safety concerns. Methodology: Medline, Scopus and Embase were searched until April 2024 for randomized controlled trials (RCTs) comparing PCB versus UCB in patients undergoing coronary ISR. Primary outcomes were in-segment late lumen loss (LLL), binary restenosis, target lesion revascularization (TLR), major adverse cardiac events (MACE), and mortality. Secondary outcomes included in-stent LLL, in-stent binary restenosis, myocardial infarction (MI), cardiac death, target vessel MI, and target vessel revascularization (TVR). Results: This meta-analysis includes seven RCTs with 1,408 patients (PCB = 864, UCB = 544). PCB significantly reduced in-segment LLL (MD= -0.50, 95% CI [-0.67, -0.33]; P < 0.00001), in-segment binary restenosis (RR= 0.25, 95% CI [0.14, 0.45]; P < 0.00001), target lesion revascularization (RR= 0.43, 95% CI [0.32, 0.58]; P < 0.00001), mortality (RR=0.56, 95% CI [0.39, 0.80]; P=0.001), and MACE (RR= 0.36, 95% CI [0.25, 0.51]; P < 0.00001). PCB also significantly decreased in-stent LLL (MD= -0.52, 95% CI [-0.72, -0.32]; P < 0.00001), in-stent binary restenosis (RR = 0.19, 95% CI [0.11, 0.35]; P < 0.00001), and TVR (RR = 0.45, 95% CI [0.29, 0.70]; P = 0.0003). PCB showed a short-term reduction in MACE and target lesion revascularization at 6 months, 1 year and 3 years of followup. No difference was observed in MI, cardiac death, or target vessel MI. Conclusion: In patients with coronary ISR, PCB are associated with reduced in-segment LLL, in-segment binary restenosis events, target lesion revascularization, mortality, MACE, in-stent LLL, in-stent binary restenosis and target vessel revascularization.

Introduction Drug-coated balloon angioplasty with paclitaxel-eluting devices (PCB) is an established treatment for coronary in-stent restenosis (ISR). Using a new biolimus-coated balloon (BCB) or sirolimus-coated balloon (SCB) may be non-inferior to using a standard PCB. This study aimed to do a meta-analysis comparing outcomes in patients undergoing treatment for ISR with BCB or SCB vs PCB. Methods Pubmed, SCOPUS and Cochrane Central were searched for cohort studies and randomized controlled trials (RCTs) that directly compared "-limus" coated balloons (BCB or SCB) to PCB for the treatment of in-stent restenosis. Outcomes of interest were: target lesion revascularization (TLR), stent thrombosis, late lumen loss (LLL), minimal lumen diameter (MLD), myocardial infarction (MI), major adverse cardiovascular events (MACE) and diameter stenosis. The results were expressed in risk ratio (RR) or mean difference (MD). Statistical analysis was performed using Review Manager and heterogeneity was assessed with I2 statistics. Results We included 1000 patients from six studies, of which five were randomised controlled trials. BCB or SCB were used to treat ISR in 534 (53.4%) patients. The follow-up period ranged from 6 to 12 months. TLR (RR 1.36; CI 0.74, 2.50; P = 0.32), stent thrombosis (RR 0.33; CI 0.05, 2.07; P = 0.24), MI (OR 1.06; CI 0.27, 4.15; P = 0.94), MACE (RR 1.10; CI 0.50, 2.39; P = 0.81) and diameter stenosis (MD 3.55; CI -1.91, 9.02; P = 0.20) showed no significant differences between treatment groups. LLL (MD -0.02; CI -0.10, 0.06; P = 0.57) and MLD (MD -0.03; CI -0.13, 0.08; P = 0.61) also did not show any relevant differences between the two treatments. Conclusions In patients treated with a drug-coated balloon for ISR, the use of a Biolimus-coated balloon or Sirolimus-coated balloon did not show any significant difference regarding the risk of TLR, stent thrombosis, MI, MACE, diameter stenosis, LLL or MLD when compared to a Paclitaxel-coated balloon. Further research is needed to fully unveil the potential benefits of these novel devices, since our study did not achieve statistical significance for non-inferiority.

现在，冠的干预戏剧性地在 thedrug-eluting stent 时代被改进了。drug-eluting stent 代表它显著地减少的主导的经皮的冠的干预形式 beacause 剩余的合并率与赤裸的心理 stent 相比。如此的利益开始在冠的容器被表明在直径的 3 公里或更多。然而，在冠的 stent 培植以后的休息合并被容器尺寸和长度影响， ands 帐篷吸藏在小容器是更经常的。在 coronarys tenting 以后的休息合并的主要原因是从光滑肌肉的房间以及细胞外的矩阵生产的增长和迁居的 neointimal 增生。很多全身的 pharmacologic 和附属 device-basedapproaches 在进一步在小型机关枪的一种以后降低休息合并的风险是无效的叮当响。最新，打断细胞的复制的代理人的地点特定的交货在禁止 neointimal 增生显示出大诺言。特别地，基于聚合物， sirolimus-eluting andpaclitaxels-eluting stent 证明了在在本国的冠的动脉的以前未经治疗的损害减少休息合并的风险安全、有效。但是小容器和复杂损害干预仍然是争论的。这研究是在小容器(直径 <3 公里) 在复杂损害评估 drug-elutingstent 的申请。

We are presenting an extension of a previously published trial on the efficacy and safety of a paclitaxel-coated balloon in coronary ISR in a larger patient population and after a complete follow-up of 2 years. Hundred eight patients were enrolled in two separately randomized, double-blind multicenter trials on efficacy and safety using an identical protocol. Patients were treated by the paclitaxel-coated (3 microg/mm(2) balloon surface; Paccocath) or an uncoated balloon. The main inclusion criteria were a diameter stenosis of >or=70% and <30 mm length with a vessel diameter of 2.5-3.5 mm. The primary endpoint was angiographic late lumen loss in-segment. Secondary endpoints included binary restenosis rate and major adverse cardiovascular events (MACE). Quantitative coronary angiography revealed no differences in baseline parameters. After six months in-segment late lumen loss was 0.81 +/- 0.79 mm in the uncoated balloon group vs. 0.11 +/- 0.45 mm (P < 0.001) in the drug-coated balloon group resulting in a binary restenosis rate of 25/49 vs. 3/47 (P < 0.001). Until 12 months post procedure 20 patients in the uncoated balloon group compared to two patients in the coated balloon group required target lesion revascularization (P = 0.001). Between 12 and 24 only two MACE were recorded, a stroke in the uncoated and a target lesion revascularization in the coated balloon group. Treatment of coronary ISR with paclitaxel-coated balloon catheters persistently reduces repeat restenosis up to 2 years. (ClinicalTrials.gov Identifier: NCT00106587, NCT00409981).

Background: Drug-coated balloon (DCB) angioplasty with paclitaxel-eluting devices is an established treatment for coronary in-stent restenosis (ISR). Limus-coated balloons have emerged as an alternative. We aimed to perform a meta-analysis comparing clinical and angiographic outcomes between limus-coated balloons (LCB) and paclitaxel-coated balloons (PCB) in coronary ISR. Methods: Databases were searched for randomized and non-randomized studies comparing LCB with PCB in patients with coronary ISR. Angiographic outcomes included percent diameter stenosis and in-segment late lumen loss (mm) as assessed by quantitative coronary angiography (QCA). Clinical outcomes included a composite of cardiac death, target lesion myocardial infarction (MI), and target lesion revascularization (TLR). Statistical analysis was performed using Review Manager (Cochrane Collaboration). Results: A total of 1,224 patients from 7 studies were included, 5 of which were randomized controlled trials. PCBs were used to treat coronary ISR in 577 (47%) patients. The mean follow-up was 13.7±4.5 months. The mean age was 66±10 years, with 76.3% being male. Type 2 diabetes mellitus was present in 44.4% of the patients, and 31.5% had a prior MI. There were no significant differences between PCB and LCB in terms of percent diameter stenosis (mean difference: -4.58%, 95% CI: -10.79 to 1.62, P = 0.15) or in in-segment late lumen loss (mean difference: 0.02 mm, 95% CI: -0.07 to 0.11, P = 0.72) at follow-up QCA. At 12 months, there were no significant differences in the composite outcome of cardiac death, target lesion MI, and TLR (RR: 1.01, 95% CI: 0.77 to 1.32, P = 0.97) between groups. LCB showed similar TLR rates compared to PCBs (RR: 0.64, 95% CI: 0.30 to 1.34, P = 0.23) at 12 months (Figures 1A and 1B). Conclusion: For patients with coronary in-stent restenosis, both paclitaxel-coated and limus-coated balloons offer effective treatment options with comparable clinical and angiographic outcomes. This provides reassurance and flexibility in treatment choices. The trend favoring PCBs in percent diameter stenosis warrants further investigation in larger, well-powered studies to compare these DCB types in similar populations.

Drug-coated balloons are a cornerstone of a "leave nothing behind" strategy in percutaneous coronary intervention. While paclitaxel-coated balloons (PCBs) are established, sirolimus-coated balloons (SCBs) represent a newer alternative. This meta-analysis integrates the latest evidence to compare the efficacy and safety of SCBs versus PCBs for coronary artery disease. We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, prospectively registered with International Prospective Register of Systematic Reviews (CRD420251157954). We searched PubMed, Embase, and Cochrane Central Register of Controlled Trial through September 2025 for randomized controlled trials and observational studies comparing PCB-only with SCB-only percutaneous coronary intervention. The primary clinical outcome was target lesion failure at 12 months. Key angiographic outcomes included in-segment late lumen loss, minimal lumen diameter, and diameter stenosis (DS). Fourteen studies (8 randomized controlled trials and 6 observational) with 6420 patients were included (PCB: n = 2042; SCB: n = 4378). The risk of target lesion failure was comparable between SCBs and PCBs [8.5% vs 9.2%; odds ratio 0.86, 95% (confidence interval) CI 0.71-1.05; P = 0.15], with no differences in its individual components. However, PCBs demonstrated superior angiographic outcomes, with significantly lower late lumen loss [Mean Difference (MD) -0.09 mm, 95% CI -0.15 to -0.01; P = 0.02] and larger minimal lumen diameter (MD 0.08 mm, 95% CI 0.01-0.14; P = 0.02). The reduction in DS with PCBs was not statistically significant (MD -2.11%, 95% CI -4.75 to 0.52; P = 0.12). This angiographic advantage was primarily driven by comparisons with the phospholipid-encapsulated SCB (MagicTouch). SCBs and PCBs demonstrate comparable clinical safety and efficacy at 1-year follow-up. Despite this, PCBs maintain an angiographic advantage, which is significantly influenced by the specific SCB excipient technology.

The SABRE Trial (Sirolimus Angioplasty Balloon for Coronary In-Stent Restenosis): Angiographic Results and 1-Year Clinical Outcomes

We aimed to evaluate the safety and performance of a magnesium-based sirolimus-eluting metal scaffold at three-year follow-up to assess vessel response two years beyond scaffold resorption. BIOSOLVE-II is an international, multicentre first-in-man study, including 123 patients with de novo lesions. Predilatation was mandatory and post-dilatation was left to the discretion of the investigators. Dual antiplatelet therapy was recommended for six months. At three years, 91.1% of patients were angina-free and 8.0% were on dual antiplatelet therapy. The target lesion failure rate was 6.8% (n=8: two cardiac deaths, one target vessel myocardial infarction and five target lesion revascularisations). No probable or definite scaffold thrombosis was observed. Imaging follow-up was voluntary and serial angiographic assessment at 6, 12, and 36 months was available in 25 patients. In these, a slight increase in in-segment and in-scaffold late lumen loss and diameter stenosis was observed between 12 and 36 months (by 0.11±0.28 mm and 0.13±0.30 mm for late lumen loss, and by 3.8±10.1% and 4.1±10.2% for diameter stenosis). Two years beyond the resorption period of a sirolimus-eluting bioresorbable metal scaffold built from a proprietary magnesium alloy, complication rates remained low. In the patients with serial angiographic assessment, late lumen loss and diameter stenosis did not increase substantially beyond the resorption period.

Drug-coated balloons (DCB) are increasingly utilized for treating in-stent restenosis (ISR), yet the comparative efficacy of limus-coated balloons (LCBs) versus paclitaxel-coated balloons (PCBs) remains uncertain. The aim of this study is to compare the clinical and angiographic outcomes of LCB versus PCBs in treating ISR. We searched PubMed, Embase, and ClinicalTrials.gov through July 2025 for RCTs comparing LCBs versus PCBs in patients with ISR. The primary outcome was late lumen loss (LLL). Secondary outcomes included percentage diameter stenosis (%DS), minimal lumen diameter (MLD), and binary restenosis at 6-12 months and target lesion revascularization (TLR), target lesion failure (TLF), target vessel myocardial infarction, cardiac death, and stent thrombosis at 12 months. Mean differences (MDs) were calculated for continuous outcomes and relative risks (RRs) for binary outcomes. Six RCTs with 968 patients (512 LCB, 456 PCB) showed statistical non-inferiority for LLL with an MD of 0.06mm (-0.07 to 0.18, P for non-inferiority < 0.001, I2 = 65%) based on the prespecified 0.20mm margin. No significant differences were found in other angiographic outcomes: MD of 3.13 (-1.07 to 7.33, p = 0.14) for %DS, - 0.07 (-0.17 to 0.03, p = 0.15) for MLD, and RR of 1.32 (0.86 to 2.03, p = 0.21) for binary restenosis. Clinical outcomes were comparable with a non-significant trend toward higher TLR (RR: 1.23 [0.87 to 1.75], P = 0.24) and TLF (1.19 [0.88 to 1.63], P = 0.26) in LCB arm. LCBs are statistically non-inferior to PCBs for ISR treatment regarding late lumen loss, with considerable heterogeneity. Given the inconclusiveness of angiographic outcomes and marginally better clinical outcomes in PCBs, the conduct of larger trials seems necessary.

Treatment of in-stent restenosis (ISR) accounts for 10% of percutaneous coronary interventions in the USA. Paclitaxel-coated balloons (PCBs) are an alternative to uncoated balloons (UCBs) for ISR. We systematically searched PubMed, Scopus, and Cochrane Central for studies comparing PCB with UCB in treating ISR. Outcomes included late lumen loss, binary restenosis, target lesion revascularization (TLR), and major adverse cardiovascular events (MACE). Eight trials including 1410 patients [PCB in 865 (61%), follow-up 6 months to 10 years) were identified. Angiographic outcomes of late lumen loss [mean difference: -0.50 mm; 95% confidence interval (CI): -0.66 to -0.33; P < 0.01] and binary restenosis [relative risk (RR): 0.22; 95% CI: 0.13-0.40; P < 0.01] at 6-8 months were lower with PCB. TLR at 6 months (RR: 0.16; 95% CI: 0.06-0.40; P < 0.001) and 1 year (RR: 0.45; 95% CI: 0.31-0.66; P < 0.001), MACE at 6 months (RR: 0.25; 95% CI: 0.16-0.38; P < 0.001), MACE at 3-5 years (RR: 0.54; 95% CI: 0.37-0.80; P = 0.002), and TLR at 3-5 years (RR: 0.51; 95% CI: 0.29-0.90; P = 0.021) were lower with PCB. Meta-regression revealed that ISR lesions in the left anterior descending artery were associated with lower rates of binary restenosis while the opposite was observed for left circumflex lesions. Revascularization of coronary ISR with PCB is associated with reduced late lumen loss, binary restenosis, TLR, CCE, and MACE. PCB may be a preferred strategy for coronary ISR.

Treatment of in-stent restenosis with paclitaxel-coated balloon catheter as compared with plain balloon angioplasty has shown surprisingly low late lumen loss at 6 months and fewer major adverse cardiac events up to 2 years. We compared the efficacy and safety of a paclitaxel-coated balloon with a paclitaxel-eluting stent as the current standard of care. One hundred thirty-one patients with coronary in-stent restenosis were randomly assigned to treatment by a paclitaxel-coated balloon (3 microg/mm2) or a paclitaxel-eluting stent. The main inclusion criteria encompassed diameter stenosis of > or =70% and < or =22 mm in length, with a vessel diameter of 2.5 to 3.5 mm. The primary end point was angiographic in-segment late lumen loss. Quantitative coronary angiography revealed no differences in baseline parameters. At 6 months follow-up, in-segment late lumen loss was 0.38+/-0.61 mm in the drug-eluting stent group versus 0.17+/-0.42 mm (P=0.03) in the drug-coated balloon group, resulting in a binary restenosis rate of 12 of 59 (20%) versus 4 of 57 (7%; P=0.06). At 12 months, the rate of major adverse cardiac events were 22% and 9%, respectively (P=0.08). This difference was primarily due to the need for target lesion revascularization in 4 patients (6%) in the coated-balloon group, compared with 10 patients (15%) in the stent group (P=0.15). Treatment of coronary in-stent restenosis with the paclitaxel-coated balloon was at least as efficacious and as well tolerated as the paclitaxel-eluting stent. For the treatment of in-stent restenosis, inhibition of re-restenosis does not require a second stent implantation.

Background Bifurcation angles may have an impact on the clinical outcomes of crush stenting. We sought to compare high (≥60°) with low (&lt;60°) bifurcation angle in patients who underwent either classical or double kissing (DK) crush stenting for bifurcation lesions from the DKCRUSH-1 data base. Methods There were 212 patients with 220 lesions, some with low-angle (n=138) and some with high-angle (n=74). Angiography was indexed at 8-month after procedure. Primary endpoint was the occurrence of major adverse cardiac events (MACEs), defined as cardiac death, myocardial infarction and target lesion revascularization (TLR). Secondary endpoint included late lumen loss, the rate of restenosis, and final kissing balloon inflation (FKBI). Results At 8 months, clinical follow-up was 100%; angiographic follow-up was 75% in the low-angle group and 83.3% in the high-angle group. There were no significant differences in the FKBI between the high-angle group (91.43%) and the low-angle group (82.39%). In the high angle group, there was a significant difference in contrast volume used (P=0.005) but no significant difference in acute gain, minimum lumen diameter (MLD), late loss and diameter stenosis in the pre-bifurcation segment, post-bifurcation segment or side branch. When lesions were assigned into with-(n=133) and without-FKBI (n=42), significant side-branch late loss was seen in the group without-FKBI ((0.65±0.49) mm vs (0.47±0.62) mm, P=0.02), with a resultant greater restenosis rate (37.68% vs 18.32%, P=0.001). No difference was detected in the MACE free survival rate between the high and low angle groups (82.39% vs 82.36%, P=0.84). The rate of stent thrombosis tended to be higher in the lower-angle group although there was no significant difference (P=0.38). The TLR free survival rate was 87.2% in the with-FKBI group vs 73.5% in the without-FKBI group (P=0.001). Cox regression analysis showed that the independent predictors for target vessel revascularization were the side branch stent MLD post stenting (hazard ratios (HR) 1.028, 95% CI 2.357–16.233, P=0.002), lack of FKBI (HR 4.910, 95% CI 4.706–8.459, P=0.001) and unsatisfactory kissing (HR 3.120, 95% CI 2.975–5.431, P=0.001). Conclusions Bifurcation angles do not influence the clinical outcome of crush stenting. Successful final kissing balloon inflation, regardless of bifurcation angles, can predict TLR.

Background: At present, there are a variety of treatment strategies for percutaneous coronary intervention. The role of drug-coated balloon (DCB) in the treatment of side branch for de novo coronary bifurcated lesions (CBL) is unclear. Objective: To examine the effect of DCB in side branch protection for de novo CBL. Methods: Electronic databases, including Pubmed, Embase, the Web of science, Cochrance library, CNKI, CBM, WanFang Data and VIP were searched for studies that compared DCB with non-drug-coated balloon (NDCB) in side branch protection for de novo CBL from inception through July7th 2021. The primary outcome was target lesion revascularization (TLR). Secondary clinical outcomes included myocardial infarction (MI), cardiac death (CD). The angiographic outcomes included side branch late lumen loss (LLL), minimum lumen diameter (MLD), diameter stenosis (DS) and binary restenosis (BR). The target lesion failure (TLF) was also analyzed. Results: A total of 10 studies, including 5 randomized controlled trials and 5 non-randomized observational studies, with 934 patients were included. Meta-analysis results of angiographic outcomes suggested that DCB group had the less LLL, DS and BR and the higher MLD compared with NDCB group at follow-up (P＜0.05). Meta-analysis results of clinical outcomes suggested that the significant difference in the TLR, MI and CD between DCB group and NDCB group has not been found yet (P＞0.05). However, the MACE of DCB group was significantly less than that of NDCB group at 9-month follow-up [OR=0.21, 95%CI (0.05, 0.84), P=0.03] and 12-month follow-up [OR=0.45, 95%CI (0.22, 0.90), P=0.02]. In addition, there was no significant difference in TLF between DCB group and NDCB group (P＞0.05). Conclusions: DCB had great effect in side branch protection for de novo CBL at short and medium-term follow-up with no reduction in the procedural success rate. Systematic Review Registration Number: PROSPERO (CRD42021267426)

Background: At present, there are a variety of treatment strategies for percutaneous coronary intervention. The role of drug-coated balloon (DCB) in the treatment of side branch for de novo coronary bifurcated lesions (CBL) is unclear.Objective: To examine the effect of DCB in side branch protection for de novo CBL.Methods: Electronic databases, including Pubmed, Embase, the Web of science, Cochrance library, CNKI, CBM, WanFang Data and VIP were searched for studies that compared DCB with non-drug-coated balloon (NDCB) in side branch protection for de novo CBL from inception through July 7th, 2021. The primary outcome was target lesion revascularization (TLR). Secondary clinical outcomes included myocardial infarction (MI), cardiac death (CD). The angiographic outcomes included side branch late lumen loss (LLL), minimum lumen diameter (MLD), diameter stenosis (DS) and binary restenosis (BR). The target lesion failure (TLF) was also analyzed.Results: A total of 10 studies, including 5 randomized controlled trials and 5 non-randomized observational studies, with 934 patients were included. Meta-analysis results of angiographic outcomes suggested that DCB group had the less LLL, DS and BR and the higher MLD compared with NDCB group at follow-up (P < 0.05). Meta-analysis results of clinical outcomes suggested that the significant difference in the TLR, MI and CD between DCB group and NDCB group has not been found yet (P > 0.05). However, the MACE of DCB group was significantly less than that of NDCB group at 9-month follow-up [OR = 0.21, 95%CI (0.05, 0.84), P = 0.03] and 12-month follow-up [OR = 0.45, 95%CI (0.22, 0.90), P = 0.02]. In addition, there was no significant difference in TLF between DCB group and NDCB group (P > 0.05).Conclusions: DCB had great effect in side branch protection for de novo CBL at short and medium-term follow-up with no reduction in the procedural success rate.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=267426, PROSPERO [Identifier: CRD42021267426].