Robustness assessment of cardiovascular meta-analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

YOU Yueyuan ¹ , ZHANG Guiying ¹ , WANG Ling ² ,  LI Jing ¹

1. Research Center of Clinical Epidemiology and Evidence Based Medicine, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;
2. Department of Cardiology, The People's Hospital of Mianyang, Mianyang, 621000, Sichuan, P. R. China;

Corresponding author：

LI Jing, Email: lijing68@hotmail.com

Keywords：

Cardiovascular; meta-analysis; robustness; fragility index

DOI：

10.7507/1007-4848.202307034

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To evaluate the robustness of cardiovascular meta-analysis with use of fragility index. Methods By searching PubMed, EMbase, and Web of Science databases from 2018 to 2022, relevant literature on cardiovascular meta-analysis was systematically collected and the fragility indexes were calculated; Spearman correlation analysis was used to explore the relationship between fragility index and sample size, total number of events, effect size and its confidence interval width. Results A total of 212 meta-analyses from 29 articles were included, with a median fragility index of 11 (5, 25), a median sample size of 10301 (3384, 48330), and a median total number of events of 360 (129, 1309). Most meta-analyses chose relative risk as the effect measure (179/212), and chose Mantel-Haenszel method (102/212) and random effects model (153/212). The fragility index was positively correlated with the sample size (r_s=0.56, P<0.05) and the total number of events (r_s=0.61, P<0.05), and negatively correlated with confidence interval width of the effect size (r_s=−0.52, P<0.05). No statistically significant results were obtained in the correlation between the fragility index and effect size. Conclusion The fragility indexes of cardiovascular meta-analyses published in comprehensive journals of high impact factors and professional cardiovascular journals are generally low, and therefore lack robustness. Fragility index is suggested to be reported in medical researches, assisting in explaining the P-value.

Citation： YOU Yueyuan, ZHANG Guiying, WANG Ling, LI Jing. Robustness assessment of cardiovascular meta-analysis. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2024, 31(2): 209-215. doi: 10.7507/1007-4848.202307034 Copy

1.	Guyatt GH, Oxman AD, Kunz R, et al. What is "quality of evidence" and why is it important to clinicians? BMJ, 2008, 336(7651): 995-998.
2.	Sutton AJ, Higgins JP. Recent developments in meta-analysis. Stat Med, 2008, 27(5): 625-650.
3.	Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol, 2011, 64(4): 383-394.
4.	Pearson K. Report on certain enteric fever inoculation statistics. Br Med J, 1904, 2(2288): 1243-1246.
5.	刘建平, 夏芸. 中文期刊发表的中医药系统综述或Meta-分析文章的质量评价. 中国中西医结合杂志, 2007, 27(4): 306-311.
6.	Moher D, Soeken K, Sampson M, et al. Assessing the quality of reports of systematic reviews in pediatric complementary and alternative medicine. BMC Pediatr, 2002, 2: 3.
7.	Ioannidis JP. The mass production of redundant, misleading, and conflicted systematic reviews and meta-analyses. Milbank Q, 2016, 94(3): 485-514.
8.	Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. J Clin Epidemiol, 2009, 62(10): 1006-1012.
9.	Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: A critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ, 2017, 358: j4008.
10.	Atal I, Porcher R, Boutron I, et al. The statistical significance of meta-analyses is frequently fragile: Definition of a fragility index for meta-analyses. J Clin Epidemiol, 2019, 111: 32-40.
11.	Walsh M, Srinathan SK, McAuley DF, et al. The statistical significance of randomized controlled trial results is frequently fragile: A case for a fragility index. J Clin Epidemiol, 2014, 67(6): 622-628.
12.	Feinstein AR. The unit fragility index: An additional appraisal of "statistical significance" for a contrast of two proportions. J Clin Epidemiol, 1990, 43(2): 201-209.
13.	Del Paggio JC, Tannock IF. The fragility of phase 3 trials supporting FDA-approved anticancer medicines: A retrospective analysis. Lancet Oncol, 2019, 20(8): 1065-1069.
14.	Shen Y, Cheng X, Zhang W. The fragility of randomized controlled trials in intracranial hemorrhage. Neurosurg Rev, 2019, 42(1): 9-14.
15.	Hayes J, Zuercher M, Gai N, et al. The fragility index of randomized controlled trials in pediatric anesthesiology. Can J Anaesth, 2023, 70(9): 1449-1460.
16.	Javidan A, Benipal H, Vi L, et al. Assessing the robustness of positive vascular surgery randomized controlled trials using their fragility index. J Vasc Surg, 2023, S0741-5214(23): 01288-0.
17.	Das S, Xaviar S. Calculation of the fragility index of randomized controlled trials in epilepsy published in twelve major journals. Epilepsy Res, 2020, 159: 106258.
18.	Volovici V, Vogels VI, Dammers R, et al. Neurosurgical evidence and randomized trials: The fragility index. World Neurosurg, 2022, 161: 224-229.
19.	Maldonado DR, Go CC, Huang BH, et al. The fragility index of hip arthroscopy randomized controlled trials: A systematic survey. Arthroscopy, 2021, 37(6): 1983-1989.
20.	Li H, Liang Z, Meng Q, et al. The fragility index of randomized controlled trials for preterm neonates. Front Pediatr, 2022, 10: 876366.
21.	Vargas M, Marra A, Buonanno P, et al. Fragility index and fragility quotient in randomized controlled trials on corticosteroids in ARDS due to COVID-19 and non-COVID-19 etiology. J Clin Med, 2021, 10(22): 5287.
22.	Khan MS, Ochani RK, Shaikh A, et al. Fragility index in cardiovascular randomized controlled trials. Circ Cardiovasc Qual Outcomes, 2019, 12(12): e005755.
23.	Ali ZA, Gao R, Kimura T, et al. Three-year outcomes with the absorb bioresorbable scaffold: Individual-patient-data meta-analysis from the ABSORB randomized trials. Circulation, 2018, 137(5): 464-479.
24.	Bangalore S, Toklu B, Patel N, et al. Newer-generation ultrathin strut drug-eluting stents versus older second-generation thicker strut drug-eluting stents for coronary artery disease. Circulation, 2018, 138(20): 2216-2226.
25.	Hao Q, Tampi M, O'Donnell M, et al. Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: Systematic review and meta-analysis. BMJ, 2018, 363: k5108.
26.	Koskinas KC, Siontis GCM, Piccolo R, et al. Effect of statins and non-statin LDL-lowering medications on cardiovascular outcomes in secondary prevention: A meta-analysis of randomized trials. Eur Heart J, 2018, 39(14): 1172-1180.
27.	McIntyre WF, Um KJ, Alhazzani W, et al. Association of vasopressin plus catecholamine vasopressors vs. catecholamines alone with atrial fibrillation in patients with distributive shock: A systematic review and meta-analysis. JAMA, 2018, 319(18): 1889-1900.
28.	Navarese EP, Robinson JG, Kowalewski M, et al. Association between baseline LDL-C level and total and cardiovascular mortality after LDL-C lowering: A systematic review and meta-analysis. JAMA, 2018, 319(15): 1566-1579.
29.	Nazha B, Pandya B, Cohen J, et al. Periprocedural outcomes of direct oral anticoagulants versus warfarin in nonvalvular atrial fibrillation. Circulation, 2018, 138(14): 1402-1411.
30.	Barbarawi M, Kheiri B, Zayed Y, et al. Vitamin D supplementation and cardiovascular disease risks in more than 83 000 individuals in 21 randomized clinical trials: A meta-analysis. JAMA Cardiol, 2019, 4(8): 765-776.
31.	Jones DA, Weeraman D, Colicchia M, et al. The impact of cell therapy on cardiovascular outcomes in patients with refractory angina. Circ Res, 2019, 124(12): 1786-1795.
32.	Mahmoud AN, Gad MM, Elgendy AY, et al. Efficacy and safety of aspirin for primary prevention of cardiovascular events: A meta-analysis and trial sequential analysis of randomized controlled trials. Eur Heart J, 2019, 40(7): 607-617.
33.	Shehata N, Mistry N, da Costa BR, et al. Restrictive compared with liberal red cell transfusion strategies in cardiac surgery: A meta-analysis. Eur Heart J, 2019, 40(13): 1081-1088.
34.	Stone GW, Kimura T, Gao R, et al. Time-varying outcomes with the absorb bioresorbable vascular scaffold during 5-year follow-up: A systematic meta-analysis and individual patient data pooled study. JAMA Cardiol, 2019, 4(12): 1261-1269.
35.	Wang KL, Lopes RD, Patel MR, et al. Efficacy and safety of reduced-dose non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: A meta-analysis of randomized controlled trials. Eur Heart J, 2019, 40(19): 1492-1500.
36.	Zheng SL, Roddick AJ. Association of aspirin use for primary prevention with cardiovascular events and bleeding events: A systematic review and meta-analysis. JAMA, 2019, 321(3): 277-287.
37.	Bainey KR, Engstrøm T, Smits PC, et al. Complete vs. culprit-lesion-only revascularization for ST-segment elevation myocardial infarction: A systematic review and meta-analysis. JAMA Cardiol, 2020, 5(8): 881-888.
38.	Bangalore S, Maron DJ, Stone GW, et al. Routine revascularization versus initial medical therapy for stable ischemic heart disease: A systematic review and meta-analysis of randomized trials. Circulation, 2020, 142(9): 841-857.
39.	Chiarito M, Sanz-Sánchez J, Cannata F, et al. Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: A systematic review and meta-analysis. Lancet, 2020, 395(10235): 1487-1495.
40.	Marsico F, Paolillo S, Gargiulo P, et al. Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease: A meta-analysis of randomized controlled trials. Eur Heart J, 2020, 41(35): 3346-3358.
41.	Pavasini R, Biscaglia S, Barbato E, et al. Complete revascularization reduces cardiovascular death in patients with ST-segment elevation myocardial infarction and multivessel disease: Systematic review and meta-analysis of randomized clinical trials. Eur Heart J, 2020, 41(42): 4103-4110.
42.	Zannad F, Ferreira JP, Pocock SJ, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: A meta-analysis of the EMPEROR-reduced and DAPA-HF trials. Lancet, 2020, 396(10254): 819-829.
43.	Cai T, Abel L, Langford O, et al. Associations between statins and adverse events in primary prevention of cardiovascular disease: Systematic review with pairwise, network, and dose-response meta-analyses. BMJ, 2021, 374: n1537.
44.	Fiolet ATL, Opstal TSJ, Mosterd A, et al. Efficacy and safety of low-dose colchicine in patients with coronary disease: A systematic review and meta-analysis of randomized trials. Eur Heart J, 2021, 42(28): 2765-2775.
45.	Galli M, Benenati S, Capodanno D, et al. Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: A systematic review and meta-analysis. Lancet, 2021, 397(10283): 1470-1483.
46.	Trifan G, Gorelick PB, Testai FD. Efficacy and safety of using dual versus monotherapy antiplatelet agents in secondary stroke prevention: Systematic review and meta-analysis of randomized controlled clinical trials. Circulation, 2021, 143(25): 2441-2453.
47.	Turagam MK, Musikantow D, Whang W, et al. Assessment of catheter ablation or antiarrhythmic drugs for first-line therapy of atrial fibrillation: A meta-analysis of randomized clinical trials. JAMA Cardiol, 2021, 6(6): 697-705.
48.	Guedeney P, Giustino G, Sorrentino S, et al. Efficacy and safety of alirocumab and evolocumab: A systematic review and meta-analysis of randomized controlled trials. Eur Heart J, 2019, ehz430.
49.	Kite TA, Kurmani SA, Bountziouka V, et al. Timing of invasive strategy in non-ST-elevation acute coronary syndrome: A meta-analysis of randomized controlled trials. Eur Heart J, 2022, 43(33): 3148-3161.
50.	Costa F, Montalto C, Branca M, et al. Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: A meta-analysis of randomized trials. Eur Heart J, 2023, 44(11): 954-968.
51.	Khairani CD, Bejjani A, Piazza G, et al. Direct oral anticoagulants vs. vitamin K antagonists in patients with antiphospholipid syndromes: Meta-analysis of randomized trials. J Am Coll Cardiol, 2023, 81(1): 16-30.
52.	Bertaggia L, Baiardo Redaelli M, Lembo R, et al. The fragility index in peri-operative randomised trials that reported significant mortality effects in adults. Anaesthesia, 2019, 74(8): 1057-1060.
53.	Chase Kruse B, Matt Vassar B. Unbreakable? An analysis of the fragility of randomized trials that support diabetes treatment guidelines. Diabetes Res Clin Pract, 2017, 134: 91-105.
54.	Go CC, Maldonado DR, Go BC, et al. The fragility index of total hip arthroplasty randomized control trials: A systematic review. J Am Acad Orthop Surg, 2022, 30(9): e741-e750.
55.	Goerke K, Parke M, Horn J, et al. Are results from randomized trials in anesthesiology robust or fragile? An analysis using the fragility index. Int J Evid Based Healthc, 2020, 18(1): 116-124.
56.	Majeed M, Agrawal R, Attar BM, et al. Fragility index: How fragile is the data that support the American College of Gastroenterology guidelines for the management of Crohn's disease? Eur J Gastroenterol Hepatol, 2020, 32(2): 193-198.
57.	Anand S, Kainth D. Fragility index of recently published meta-analyses in pediatric urology: A striking observation. Cureus, 2021, 13(7): e16225.
58.	Schröder A, Muensterer OJ, Oetzmann von Sochaczewski C. Meta-analyses in paediatric surgery are often fragile: Implications and consequences. Pediatr Surg Int, 2021, 37(3): 363-367.
59.	Ruzbarsky JJ, Khormaee S, Daluiski A. The fragility index in hand surgery randomized controlled trials. J Hand Surg Am, 2019, 44(8): 698. e1-698. e7.
60.	Head ML, Holman L, Lanfear R, et al. The extent and consequences of p-hacking in science. PLoS Biol, 2015, 13(3): e1002106.
61.	Simonsohn U, Nelson LD, Simmons JP. p-curve and effect size: Correcting for publication bias using only significant results. Perspect Psychol Sci, 2014, 9(6): 666-681.

1. Guyatt GH, Oxman AD, Kunz R, et al. What is "quality of evidence" and why is it important to clinicians? BMJ, 2008, 336(7651): 995-998.
2. Sutton AJ, Higgins JP. Recent developments in meta-analysis. Stat Med, 2008, 27(5): 625-650.
3. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol, 2011, 64(4): 383-394.
4. Pearson K. Report on certain enteric fever inoculation statistics. Br Med J, 1904, 2(2288): 1243-1246.
5. 刘建平, 夏芸. 中文期刊发表的中医药系统综述或Meta-分析文章的质量评价. 中国中西医结合杂志, 2007, 27(4): 306-311.
6. Moher D, Soeken K, Sampson M, et al. Assessing the quality of reports of systematic reviews in pediatric complementary and alternative medicine. BMC Pediatr, 2002, 2: 3.
7. Ioannidis JP. The mass production of redundant, misleading, and conflicted systematic reviews and meta-analyses. Milbank Q, 2016, 94(3): 485-514.
8. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. J Clin Epidemiol, 2009, 62(10): 1006-1012.
9. Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: A critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ, 2017, 358: j4008.
10. Atal I, Porcher R, Boutron I, et al. The statistical significance of meta-analyses is frequently fragile: Definition of a fragility index for meta-analyses. J Clin Epidemiol, 2019, 111: 32-40.
11. Walsh M, Srinathan SK, McAuley DF, et al. The statistical significance of randomized controlled trial results is frequently fragile: A case for a fragility index. J Clin Epidemiol, 2014, 67(6): 622-628.
12. Feinstein AR. The unit fragility index: An additional appraisal of "statistical significance" for a contrast of two proportions. J Clin Epidemiol, 1990, 43(2): 201-209.
13. Del Paggio JC, Tannock IF. The fragility of phase 3 trials supporting FDA-approved anticancer medicines: A retrospective analysis. Lancet Oncol, 2019, 20(8): 1065-1069.
14. Shen Y, Cheng X, Zhang W. The fragility of randomized controlled trials in intracranial hemorrhage. Neurosurg Rev, 2019, 42(1): 9-14.
15. Hayes J, Zuercher M, Gai N, et al. The fragility index of randomized controlled trials in pediatric anesthesiology. Can J Anaesth, 2023, 70(9): 1449-1460.
16. Javidan A, Benipal H, Vi L, et al. Assessing the robustness of positive vascular surgery randomized controlled trials using their fragility index. J Vasc Surg, 2023, S0741-5214(23): 01288-0.
17. Das S, Xaviar S. Calculation of the fragility index of randomized controlled trials in epilepsy published in twelve major journals. Epilepsy Res, 2020, 159: 106258.
18. Volovici V, Vogels VI, Dammers R, et al. Neurosurgical evidence and randomized trials: The fragility index. World Neurosurg, 2022, 161: 224-229.
19. Maldonado DR, Go CC, Huang BH, et al. The fragility index of hip arthroscopy randomized controlled trials: A systematic survey. Arthroscopy, 2021, 37(6): 1983-1989.
20. Li H, Liang Z, Meng Q, et al. The fragility index of randomized controlled trials for preterm neonates. Front Pediatr, 2022, 10: 876366.
21. Vargas M, Marra A, Buonanno P, et al. Fragility index and fragility quotient in randomized controlled trials on corticosteroids in ARDS due to COVID-19 and non-COVID-19 etiology. J Clin Med, 2021, 10(22): 5287.
22. Khan MS, Ochani RK, Shaikh A, et al. Fragility index in cardiovascular randomized controlled trials. Circ Cardiovasc Qual Outcomes, 2019, 12(12): e005755.
23. Ali ZA, Gao R, Kimura T, et al. Three-year outcomes with the absorb bioresorbable scaffold: Individual-patient-data meta-analysis from the ABSORB randomized trials. Circulation, 2018, 137(5): 464-479.
24. Bangalore S, Toklu B, Patel N, et al. Newer-generation ultrathin strut drug-eluting stents versus older second-generation thicker strut drug-eluting stents for coronary artery disease. Circulation, 2018, 138(20): 2216-2226.
25. Hao Q, Tampi M, O'Donnell M, et al. Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: Systematic review and meta-analysis. BMJ, 2018, 363: k5108.
26. Koskinas KC, Siontis GCM, Piccolo R, et al. Effect of statins and non-statin LDL-lowering medications on cardiovascular outcomes in secondary prevention: A meta-analysis of randomized trials. Eur Heart J, 2018, 39(14): 1172-1180.
27. McIntyre WF, Um KJ, Alhazzani W, et al. Association of vasopressin plus catecholamine vasopressors vs. catecholamines alone with atrial fibrillation in patients with distributive shock: A systematic review and meta-analysis. JAMA, 2018, 319(18): 1889-1900.
28. Navarese EP, Robinson JG, Kowalewski M, et al. Association between baseline LDL-C level and total and cardiovascular mortality after LDL-C lowering: A systematic review and meta-analysis. JAMA, 2018, 319(15): 1566-1579.
29. Nazha B, Pandya B, Cohen J, et al. Periprocedural outcomes of direct oral anticoagulants versus warfarin in nonvalvular atrial fibrillation. Circulation, 2018, 138(14): 1402-1411.
30. Barbarawi M, Kheiri B, Zayed Y, et al. Vitamin D supplementation and cardiovascular disease risks in more than 83 000 individuals in 21 randomized clinical trials: A meta-analysis. JAMA Cardiol, 2019, 4(8): 765-776.
31. Jones DA, Weeraman D, Colicchia M, et al. The impact of cell therapy on cardiovascular outcomes in patients with refractory angina. Circ Res, 2019, 124(12): 1786-1795.
32. Mahmoud AN, Gad MM, Elgendy AY, et al. Efficacy and safety of aspirin for primary prevention of cardiovascular events: A meta-analysis and trial sequential analysis of randomized controlled trials. Eur Heart J, 2019, 40(7): 607-617.
33. Shehata N, Mistry N, da Costa BR, et al. Restrictive compared with liberal red cell transfusion strategies in cardiac surgery: A meta-analysis. Eur Heart J, 2019, 40(13): 1081-1088.
34. Stone GW, Kimura T, Gao R, et al. Time-varying outcomes with the absorb bioresorbable vascular scaffold during 5-year follow-up: A systematic meta-analysis and individual patient data pooled study. JAMA Cardiol, 2019, 4(12): 1261-1269.
35. Wang KL, Lopes RD, Patel MR, et al. Efficacy and safety of reduced-dose non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: A meta-analysis of randomized controlled trials. Eur Heart J, 2019, 40(19): 1492-1500.
36. Zheng SL, Roddick AJ. Association of aspirin use for primary prevention with cardiovascular events and bleeding events: A systematic review and meta-analysis. JAMA, 2019, 321(3): 277-287.
37. Bainey KR, Engstrøm T, Smits PC, et al. Complete vs. culprit-lesion-only revascularization for ST-segment elevation myocardial infarction: A systematic review and meta-analysis. JAMA Cardiol, 2020, 5(8): 881-888.
38. Bangalore S, Maron DJ, Stone GW, et al. Routine revascularization versus initial medical therapy for stable ischemic heart disease: A systematic review and meta-analysis of randomized trials. Circulation, 2020, 142(9): 841-857.
39. Chiarito M, Sanz-Sánchez J, Cannata F, et al. Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: A systematic review and meta-analysis. Lancet, 2020, 395(10235): 1487-1495.
40. Marsico F, Paolillo S, Gargiulo P, et al. Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease: A meta-analysis of randomized controlled trials. Eur Heart J, 2020, 41(35): 3346-3358.
41. Pavasini R, Biscaglia S, Barbato E, et al. Complete revascularization reduces cardiovascular death in patients with ST-segment elevation myocardial infarction and multivessel disease: Systematic review and meta-analysis of randomized clinical trials. Eur Heart J, 2020, 41(42): 4103-4110.
42. Zannad F, Ferreira JP, Pocock SJ, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: A meta-analysis of the EMPEROR-reduced and DAPA-HF trials. Lancet, 2020, 396(10254): 819-829.
43. Cai T, Abel L, Langford O, et al. Associations between statins and adverse events in primary prevention of cardiovascular disease: Systematic review with pairwise, network, and dose-response meta-analyses. BMJ, 2021, 374: n1537.
44. Fiolet ATL, Opstal TSJ, Mosterd A, et al. Efficacy and safety of low-dose colchicine in patients with coronary disease: A systematic review and meta-analysis of randomized trials. Eur Heart J, 2021, 42(28): 2765-2775.
45. Galli M, Benenati S, Capodanno D, et al. Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: A systematic review and meta-analysis. Lancet, 2021, 397(10283): 1470-1483.
46. Trifan G, Gorelick PB, Testai FD. Efficacy and safety of using dual versus monotherapy antiplatelet agents in secondary stroke prevention: Systematic review and meta-analysis of randomized controlled clinical trials. Circulation, 2021, 143(25): 2441-2453.
47. Turagam MK, Musikantow D, Whang W, et al. Assessment of catheter ablation or antiarrhythmic drugs for first-line therapy of atrial fibrillation: A meta-analysis of randomized clinical trials. JAMA Cardiol, 2021, 6(6): 697-705.
48. Guedeney P, Giustino G, Sorrentino S, et al. Efficacy and safety of alirocumab and evolocumab: A systematic review and meta-analysis of randomized controlled trials. Eur Heart J, 2019, ehz430.
49. Kite TA, Kurmani SA, Bountziouka V, et al. Timing of invasive strategy in non-ST-elevation acute coronary syndrome: A meta-analysis of randomized controlled trials. Eur Heart J, 2022, 43(33): 3148-3161.
50. Costa F, Montalto C, Branca M, et al. Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: A meta-analysis of randomized trials. Eur Heart J, 2023, 44(11): 954-968.
51. Khairani CD, Bejjani A, Piazza G, et al. Direct oral anticoagulants vs. vitamin K antagonists in patients with antiphospholipid syndromes: Meta-analysis of randomized trials. J Am Coll Cardiol, 2023, 81(1): 16-30.
52. Bertaggia L, Baiardo Redaelli M, Lembo R, et al. The fragility index in peri-operative randomised trials that reported significant mortality effects in adults. Anaesthesia, 2019, 74(8): 1057-1060.
53. Chase Kruse B, Matt Vassar B. Unbreakable? An analysis of the fragility of randomized trials that support diabetes treatment guidelines. Diabetes Res Clin Pract, 2017, 134: 91-105.
54. Go CC, Maldonado DR, Go BC, et al. The fragility index of total hip arthroplasty randomized control trials: A systematic review. J Am Acad Orthop Surg, 2022, 30(9): e741-e750.
55. Goerke K, Parke M, Horn J, et al. Are results from randomized trials in anesthesiology robust or fragile? An analysis using the fragility index. Int J Evid Based Healthc, 2020, 18(1): 116-124.
56. Majeed M, Agrawal R, Attar BM, et al. Fragility index: How fragile is the data that support the American College of Gastroenterology guidelines for the management of Crohn's disease? Eur J Gastroenterol Hepatol, 2020, 32(2): 193-198.
57. Anand S, Kainth D. Fragility index of recently published meta-analyses in pediatric urology: A striking observation. Cureus, 2021, 13(7): e16225.
58. Schröder A, Muensterer OJ, Oetzmann von Sochaczewski C. Meta-analyses in paediatric surgery are often fragile: Implications and consequences. Pediatr Surg Int, 2021, 37(3): 363-367.
59. Ruzbarsky JJ, Khormaee S, Daluiski A. The fragility index in hand surgery randomized controlled trials. J Hand Surg Am, 2019, 44(8): 698. e1-698. e7.
60. Head ML, Holman L, Lanfear R, et al. The extent and consequences of p-hacking in science. PLoS Biol, 2015, 13(3): e1002106.
61. Simonsohn U, Nelson LD, Simmons JP. p-curve and effect size: Correcting for publication bias using only significant results. Perspect Psychol Sci, 2014, 9(6): 666-681.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Robustness assessment of cardiovascular meta-analysis

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