Invasive versus conservative management of older patients with non-ST- elevation acute coronary syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Invasive versus conservative management of older patients with non-ST- elevation acute coronary syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Invasive versus conservative management of older patients with non-ST- elevation acute coronary syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials Shijie Fan, Xiang Yuan, Jun Wan, Peng Wang, Jinfeng He, Kuilin Li, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5842406/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The benefits of conservative treatment versus invasive strategies for elderly patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) remain ambiguous. Consequently, this systematic review and meta-analysis aimed to assess and compare the effects of invasive versus conservative treatment strategies in elderly patients diagnosed with NSTEACS. Methods We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to October 2024 to identify RCTs comparing invasive versus conservative management in elderly patients with non-ST-elevation acute coronary syndrome. The primary outcome was all-cause mortality at 1 year, with secondary outcome including myocardial infarction (MI). Results Seven trials (2997 patients) reported primary outcome data, with six also providing data on myocardial infarction. At 1-year follow-up, there was no difference in all-cause mortality between the invasive treatment group and the conservative treatment group (RR 1.05, 95%CI 0.94 to 1.18, I 2 = 0%) After a one-year follow-up, but invasive treatment reduce the risk of myocardial infarction (RR 0.74, 95%CI 0.57 to 0.95, I 2 = 38%). Conclusion In the elderly with Non–ST-segment elevation myocardial infarction, invasive treatment did not improve all-cause mortality at 1-year follow-up compared to conservative management. However, it was found to significantly lower the risk of myocardial infarction. Health sciences/Medical research/Outcomes research Health sciences/Cardiology/Interventional cardiology non-ST-segment elevation acute coronary syndrome myocardial infarction Meta-analysis Figures Figure 1 Figure 2 Figure 3 Introduction Ischemic heart disease is the leading cause of mortality globally, with older adults bearing a disproportionate share of this burden. 1 Between 2015 and 2050, the proportion of the global population aged 65 years and older is expected to nearly double, rising to 22%. This significant increase reflects the ongoing global trend of population aging. As the global population ages, the management of myocardial infarction (MI) in this demographic has become increasingly complex due to the higher prevalence of comorbid conditions, greater frailty, and elevated risks associated with invasive procedures. 2 Age is a well-established and widely recognized risk factor for the onset of acute coronary syndromes, with non–ST-segment elevation myocardial infarction (NSTEMI) emerging as the most common and predominant subtype in individuals aged over 70 years, a population whose risk is compounded by the presence of other age-related factors such as frailty, comorbidities, and reduced physiological reserve. 3 , 4 Current clinical practice guidelines recommend an invasive approach for managing non–ST-elevation acute coronary syndromes, which includes routine cardiac catheterization and revascularization upon admission. 5 , 6 However, there is a lack of specific invasive treatment guidelines and evidence-based recommendations for older patients with acute coronary syndromes, primarily due to their underrepresentation in clinical trials. 7 This gap ultimately results in a significant portion of this patient population being deprived of potentially beneficial invasive treatments. Previous meta-analysis has explored the differences in myocardial infarction outcomes between invasive and conservative treatments in elderly patients with NSTEACS, and the composite results of all-cause mortality and myocardial infarction were negative. 8 However, a recent large randomized controlled trial, which included a significant amount of additional data, demonstrated that invasive strategies did not lead to a reduction in the overall incidence of myocardial infarction or all-cause mortality. 9 This finding contradicts the conclusions of earlier meta-analyses and may reflect the relatively small sample sizes of the studies included in those analyses. Consequently, there is a pressing need for new analyses of these critical data. The aim of this meta-analysis is to utilize all the recent randomized controlled trials to investigate the comparative benefits of conventional invasive strategies versus conservative strategies in the elderly, particularly in relation to patients with elderly myocardial infarction. The ultimate objective is to provide robust, evidence-based recommendations to inform clinical decision-making, with the aim of improving outcomes and prognosis for this high-risk patient population. Methods Protocol and guidance Th This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 10 Furthermore, prior to commencing the study, we prospectively registered the research protocol at PROSPERO under registration number CRD42024608953. This procedure was implemented to enhance transparency and ensure compliance with established evidence-based research standards. Search strategy and selection criteria Studies were eligible for inclusion if they 1) focused on non-ST elevation acute coronary syndromes (NSTEACS), defined by clinical symptoms suggestive of acute myocardial ischemia, the absence of persistent ST-segment elevation, and elevated troponin levels, as confirmed by the local laboratory’s assay; 2) involved participants aged 70 years or older; 3) were randomized controlled trials; 4) included an intervention group that received invasive treatments (such as coronary angiography and revascularization); and 5) reported at least one of the predefined key outcomes, including myocardial infarction or mortality. Outcomes The primary outcome was 1-year all-cause mortality, while the secondary outcome focused on myocardial infarction (MI). All included studies defined MI as the occurrence of new cardiac symptoms accompanied by troponin levels exceeding the 99th percentile. Data sources and search strategy We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from inception until October, 2024. The search terms used were “Non-ST Elevated Myocardial Infarction,” “Angioplasty, Balloon, Coronary,” “Conservative Treatment,” and “Aged.” There were no limitations based on language. Table S1 in the Data Supplement outlines the comprehensive search terms employed in each database searched. Inclusion criteria Two reviewers (SF and XY) independently screened all titles and abstracts retrieved from the systematic search. To ensure the accuracy of the data, a third reviewer (YZ) was consulted to resolve any discrepancies. Any disagreements between reviewers were addressed through discussion or, if necessary, adjudicated by the third reviewer (YZ). Data extraction To ensure the integrity and reliability of the study selection process, two independent reviewers (SF and XY) conducted a thorough screening of all titles and abstracts identified during the systematic search. Any potential discrepancies or uncertainties in the data were addressed by a third reviewer (YZ), who was responsible for verifying and resolving any inconsistencies. In cases of disagreement between the two primary reviewers, the third reviewer (YZ) intervened to adjudicate the issue through discussion and consensus, ensuring that the final selection adhered to the predefined inclusion criteria. Assessment of the risk of bias Two reviewers (SF and XY) independently evaluated the risk of bias in the included trials using the Cochrane Risk of Bias-2 tool, assessing five key domains: bias due to the randomization process, deviations from intended interventions, missing outcome data, outcome measurement, and selection of reported results. 11 For each domain, a study-level score was assigned, categorizing the risk of bias as low, high, or unclear. Any disagreements between the two primary reviewers were resolved through discussion. In cases where consensus could not be reached, a final decision was made by a third reviewer (YZ), ensuring a thorough and impartial evaluation of the risk of bias across all trials. Confidence of evidence The quality of evidence for both the primary and secondary outcomes was independently evaluated by two authors (SF and XY) using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This assessment helped to determine the strength and reliability of the evidence supporting each outcome. 12 This rigorous assessment process involved categorizing the quality of evidence as high, moderate, low, or very low. Various factors were taken into consideration during this evaluation, including the study designs, the potential risk of bias in their methodologies, inconsistencies in the results, the imprecision of effect estimates, and the indirectness of the findings relative to the clinical questions posed. Data analysis Statistical analysis was performed using Review Manager (version 5.4, The Cochrane Collaboration). For binary outcomes, relative risks with 95% confidence intervals (CI) were calculated. For continuous data, we computed the mean difference (MD) with 95% CI. Heterogeneity across studies was assessed using Cochrane’s Q test and Higgins’ I² statistic, with Q values set at a significance level of 10% (p < 0.1) and I² values greater than 50% indicating substantial heterogeneity. To ensure the robustness of the results, random-effects models were applied for all outcomes. A two-sided p-value of less than 0.05 was considered statistically significant. Forest plots were generated to visualize the effect sizes and combined estimates. All analyses were conducted using two-tailed tests, with a significance threshold of p < 0.05. Publication bias If the meta-analysis included 10 or more studies, a funnel plot would be generated, and quantitative assessments would be conducted using Egger’s 13 and Begg's 14 tests to evaluate potential biases related to small-study effects. Subgroup analysis Subgroup analysis of the primary outcome was performed according to age groups. Sensitivity analysis In the sensitivity analysis, we applied a fixed-effect model and excluded studies contributing less than 5% to the overall weight to evaluate their potential influence on the pooled relative risk (RR) for mortality. Results Our initial search strategy retrieved 366 records. After removing duplicates, 227 unique records remained. We then conducted a thorough review of titles, abstracts, and full-texts, ultimately identifying 7 trials 9 , 15 – 20 that met the inclusion criteria for this systematic review. (Fig. 1) Table 1 summarizes the characteristics of the trials included in this study. These trials were published between 2012 and 2024, with sample sizes ranging from 106 to 1,518 patients. The supplementary data includes Figure S1 , which includes an evaluation of the risk of bias. The assessment revealed that the majority of studies exhibited a low risk of bias, particularly regarding random sequence generation and allocation concealment. However, the seven studies included in the analysis showed a high risk of bias in terms of blinding of both participants and personnel, as well as outcome assessment, which is probably due to the distinct differences between invasive and conservative treatments, making blinding operations challenging. Through GRADE assessment, the evidence quality for the primary outcome was rated as moderate, while the evidence quality for the secondary outcome of myocardial infarction was rated as moderate (table S2 in the Data Supplement). All seven trials reported data on the primary outcome, and six also specified data on myocardial infarction. After a one-year follow-up, we did not find any difference in all-cause mortality between the invasive treatment group and the conservative treatment group (RR 1.05, 95%CI 0.94 to 1.18, I 2 = 0%) (Fig. 2), but invasive treatment could reduce the risk of myocardial infarction (RR 0.74, 95%CI 0.57 to 0.95, I 2 = 38%) (Fig. 3). The sensitivity analysis indicated that the use of a fixed-effect model instead of a random-effects model (RR 0.74, 95% CI 0.62 to 0.88) still did not show a difference in all-cause mortality for NSTEACS patients (Table S3 in Date Supplement). Additionally, when studies contributing less than 5% to the overall weight were excluded (RR 1.04, 95%CI 0.90 to 1.19, I 2 = 7%), the primary results remained unchanged (Table S3 in Date Supplement). The subgroup results for the primary outcome in NSTEACS patients suggest that the age factor (> 70 vs. >75 vs. >80, P for interaction = 0.36) (Figure S2 in the Data Supplement). Discussion This analysis is based on seven randomized controlled trials, which included 2997 patients with Non–ST-segment elevation acute coronary syndrome. In our meta-analysis, we revealed that an invasive treatment strategy compared to a conservative strategy of the best available medical therapy, does not lead to a reduction in all-cause mortality. However, there is convincing evidence that invasive treatment lowers the risk of MI. A previous meta-analysis also examined this topic. 8 It concluded that there were differences in the outcomes of myocardial infarction (hazard ratio 0.62, 95% CI 0.44 to 0.87), but no difference was observed in all-cause mortality at one year (hazard ratio 1.03, 95% CI 0.69 to 1.53). However, this result contradicts the latest findings of a randomized controlled trial with a larger sample size that was recently released, which indicated that invasive strategies did not lower the overall incidence of myocardial infarction or all-cause mortality. 9 In comparison, we included a larger dataset comprising 2,997 patients, which is 1,518 more than in previous meta-analyses. Our main advantage lies in the greater accuracy of our results, with a narrower confidence interval, such as for all-cause mortality (95% CI 0.98 to 1.18). Globally, ischemic intervals remained largely unaffected, thereby validating the robustness of the study's findings. Cardiovascular disease is the leading cause of death worldwide, with a disproportionately higher mortality burden among older adults. Notably, individuals over the age of 75 represent the strongest negative predictor for receiving routine invasive care, with frail patients or those with comorbidities are less likely to undergo coronary angiography. 3 , 21 , 22 Guideline recommendations for managing ACS are often derived from studies that exclude older patients. More contemporary trials have frequently been underpowered and have produced inconsistent findings regarding this population. Additionally, the potential impact of age and underlying diseases on the degree of physical frailty in patients remains inadequately understood. 22 Evidence regarding the impact of frailty and comorbidities on management decisions is scarce. Therefore, clinical guidelines and evidence-based practices should inform the decision-making process, carefully considering the potential benefits and risks associated with each strategy. There are several limitations that need to be considered. Firstly, inconsistencies in the inclusion criteria, particularly the definition of age for elderly patients, have introduced variability to the research field. The variations in age within the studies may have further contributed to heterogeneity, and these parameters should be standardized in future studies. Second, there was a notable lack of frailty assessments in the studies, with only the MOSCA-FRAIL trial providing relevant data. Frailty is commonly observed in elderly patients with NSTEACS and may have a substantial impact on the potential benefits of coronary angiography and revascularization procedures. Third, the Coronavirus Disease 2019 (COVID-19) pandemic may have influenced the outcomes of several trials. 9 , 15 – 17 During this period, many patients, particularly those in the conservative treatment group, were understandably more hesitant to seek hospital care due to the heightened risk of COVID-19 infection. This reluctance was compounded by global lockdowns, social distancing measures, and concerns about overwhelming healthcare systems. As a result, patients may have postponed or avoided necessary medical interventions, potentially impacting their health outcomes. Fourth, further subgroup analyses were not feasible. Although we conducted a subgroup analysis based on age, the lack of detailed data in the included studies limited the exploration of other subgroups. For example, information on comorbidities or disease type was not consistently reported, preventing a deeper analysis of how these factors might influence treatment outcomes. Conclusions In the elderly with Non–ST-segment elevation myocardial infarction, invasive treatment did not improve all-cause mortality at 1-year follow-up compared to conservative management. However, it significantly reduced the risk of myocardial infarction. Abbreviations NSTEACS non-ST-segment elevation acute coronary syndrome MI myocardial infarction COVID-19 Coronavirus Disease 2019 GRADE Grading of Recommendation, Assessment, Development and Evaluation PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analysis CI Confidence intervals RR Relative risk OR Odds ratio MD Mean difference Declarations Funding none. Author contributions Study concept: YZ. Design: All authors. Acquisition, analysis, or interpretation of data: SF, XY, JW, PW, JH, KL, QY, JH, XL, XY, ZX, XL and YR. Statistical analysis: SF and XY. Drafting of the manuscript: SF, XY and JW. Critical revision of the manuscript for important intellectual content: All authors. Acknowledgements We acknowledge the use of GPT-based AI for language refinement in the manuscript preparation. Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Availability of data and materials All relevant data are within the manuscript and its Supporting Information files. And the data used in this study are obtained from publicly available sources. Competing interests The authors declare no competing interests. Disclosures None References Global national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390 , 1151–1210. https://doi.org/10.1016/s0140-6736(17)32152-9 (2017). Batty, J. et al. One-year clinical outcomes in older patients with non-ST elevation acute coronary syndrome undergoing coronary angiography: An analysis of the ICON1 study. Int. J. Cardiol. 274 , 45–51. https://doi.org/10.1016/j.ijcard.2018.09.086 (2019). Mills, G. B. et al. Is the contemporary care of the older persons with acute coronary syndrome evidence-based? Eur. Heart J. Open. 2 , oeab044. https://doi.org/10.1093/ehjopen/oeab044 (2022). Veerasamy, M. et al. Acute coronary syndrome among older patients: a review. Cardiol. Rev. 23 , 26–32. https://doi.org/10.1097/crd.0000000000000016 (2015). Amsterdam, E. A. et al. AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology 64, e139-e228 (2014). (2014). https://doi.org/https://doi.org/10.1016/j.jacc.2014.09.017 Roffi, M. et al. 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EuroIntervention 17 , 67–74. https://doi.org/10.4244/EIJ-D-20-00975 (2021). Hirlekar, G. et al. Percutaneous coronary intervention in the very elderly with NSTE-ACS: the randomized 80 + study. Scandinavian Cardiovasc. journal: SCJ . 54 , 315–321. https://doi.org/10.1080/14017431.2020.1781243 (2020). Sanchis, J. et al. Effect of Routine Invasive vs Conservative Strategy in Older Adults With Frailty and Non-ST-Segment Elevation Acute Myocardial Infarction: a Randomized Clinical Trial. JAMA Intern. Med. 183 , 407–415. https://doi.org/10.1001/jamainternmed.2023.0047 (2023). Sanchis, J. et al. Randomized comparison between the invasive and conservative strategies in comorbid elderly patients with non-ST elevation myocardial infarction. Eur. J. Intern. Med. 35 , 89–94. https://doi.org/10.1016/j.ejim.2016.07.003 (2016). Savonitto, S. et al. Early aggressive versus initially conservative treatment in elderly patients with non-ST-segment elevation acute coronary syndrome: a randomized controlled trial. JACC Cardiovasc. Intervent. 5 , 906–916. https://doi.org/10.1016/j.jcin.2012.06.008 (2012). Tegn, N. et al. Invasive versus conservative strategy in patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris (After Eighty study): an open-label randomised controlled trial. Lancet 387 , 1057–1065. https://doi.org/10.1016/s0140-6736(15)01166-6 (2016). Beska, B. et al. Impact of multimorbidity on long-term outcomes in older adults with non-ST elevation acute coronary syndrome in the North East of England: a multi-centre cohort study of patients undergoing invasive care. BMJ Open. 12 , e061830. https://doi.org/10.1136/bmjopen-2022-061830 (2022). Ekerstad, N. et al. Frailty is independently associated with short-term outcomes for elderly patients with non-ST-segment elevation myocardial infarction. Circulation 124 , 2397–2404. https://doi.org/10.1161/circulationaha.111.025452 (2011). Tables Table 1. Characteristics of studies included in the meta-analysis Trial Country Type of disease Age Total Participants Female （ % ） Median Timing of Angiography in the invasive group Crossover from Conservative to PCI or CABG (%) Median no. of days from admission to randomization from admission to angiography from randomization to angiography Stefano Savonitto et al., 2012 Italy NSTEACS ≥ 75 years 313 50 NR 1 day 23 1 Nicolai Tegn et al., 2016 Norway NSTEACS ≥ 80 years 457 51 3 days (Not specifically stated) NR 2 Juan Sanchis et al., 2016 Spain NSTEMI ≥ 70 years 106 47 NR NR 9 1 Geir Hirlekar et al., 2020 Sweden NSTEACS ≥ 80 years 186 45 NR NR 4 NR Adam De Belder et al., 2021 United Kingdom NSTEMI ≥ 80 years 250 47 NR 2 days 3 NR Juan Sanchis et al., 2023 Spain NSTEMI ≥ 70 years 167 53 3 days NR 10 2 V.Kunadian et al.，2024 United Kingdom NSTEMI ≥ 75 years 1518 45 5 days 3 days NR 2 NSTEACS：non–ST-segment elevation acute coronary syndromes, NSTEMI：non-ST-elevation myocardial infarction PCI：percutaneous coronary intervention, CABG：coronary artery bypass grafting, NR: not reported Additional Declarations No competing interests reported. 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Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIiWNgGAWjYDACCQjFwyZ//uMDBjYQO4E4LTL8EgzGBiRpsZGcwWAmQZQW+dnNzx5+bTvMY3C7Ia3iR9lhBn72HAOGnztwa2Gcc8zcWBak5c6BYzd7zh1mkOx5Y8DYewa3FmaJBDNpSZCWA4lttxnbDjMY3MgxYGZsw62FTSL9G1RLMlsxSIs9IS08Ejlmkh+BWiRnpLExg22RIKBFQiKnTJrhXDoPP88ZZskeIEPizLOCg714tMjPSN8m+aPM2p6NvYfxA5Ahx9+evPHBTzxawEHAy4bkUhBxAL8GYED/+ENIySgYBaNgFIxoAACE101k3i2oWwAAAABJRU5ErkJggg==","orcid":"","institution":"Center for Evidence-based Medicine, Affiliated Hospital of Chengdu University","correspondingAuthor":true,"prefix":"","firstName":"Yu","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-01-16 13:53:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5842406/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5842406/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":75518728,"identity":"2a1ab4f4-52ba-4a1e-a0ff-747b59a81a3b","added_by":"auto","created_at":"2025-02-05 11:52:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":360663,"visible":true,"origin":"","legend":"\u003cp\u003eSearch strategy and final included and excluded studies.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5842406/v1/bda4b60db0cb9ae2cdcbefbe.png"},{"id":75517905,"identity":"c1b38fdd-f96a-4b38-9c9a-3cb56a26f8e1","added_by":"auto","created_at":"2025-02-05 11:44:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":70677,"visible":true,"origin":"","legend":"\u003cp\u003eForest plots comparing: All-Cause Mortality in control and invasive groups of non-ST-elevation acute coronary syndrome patients\u003c/p\u003e\n\u003cp\u003eM–H: Mantel–Haenszel, CI: Confidence interval, df: Degrees of freedom.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5842406/v1/36b3d07e6991ff40355eb4e8.png"},{"id":75517912,"identity":"03b9a6d3-715f-47d5-b26f-36ba69cce5ff","added_by":"auto","created_at":"2025-02-05 11:44:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":66900,"visible":true,"origin":"","legend":"\u003cp\u003eForest plots comparing: myocardial infarction in control and invasive groups of non-ST-elevation acute coronary syndrome patients\u003c/p\u003e\n\u003cp\u003eM–H: Mantel–Haenszel, CI: Confidence interval, df: Degrees of freedom\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5842406/v1/a484220bd9f4fc75761abbce.png"},{"id":83111669,"identity":"7e2689b3-3e5f-4b61-ad1c-fbfa5d966b95","added_by":"auto","created_at":"2025-05-20 07:24:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1284116,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5842406/v1/515946d3-4174-4fac-b4df-941c625da20b.pdf"},{"id":75517909,"identity":"882d5a39-3e65-4bb9-beb1-ba60de1da19f","added_by":"auto","created_at":"2025-02-05 11:44:43","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":529768,"visible":true,"origin":"","legend":"","description":"","filename":"DataSupplement.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5842406/v1/7695fdf8b1239c0ce45f5253.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Invasive versus conservative management of older patients with non-ST- elevation acute coronary syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIschemic heart disease is the leading cause of mortality globally, with older adults bearing a disproportionate share of this burden.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Between 2015 and 2050, the proportion of the global population aged 65 years and older is expected to nearly double, rising to 22%. This significant increase reflects the ongoing global trend of population aging. As the global population ages, the management of myocardial infarction (MI) in this demographic has become increasingly complex due to the higher prevalence of comorbid conditions, greater frailty, and elevated risks associated with invasive procedures.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Age is a well-established and widely recognized risk factor for the onset of acute coronary syndromes, with non\u0026ndash;ST-segment elevation myocardial infarction (NSTEMI) emerging as the most common and predominant subtype in individuals aged over 70 years, a population whose risk is compounded by the presence of other age-related factors such as frailty, comorbidities, and reduced physiological reserve.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Current clinical practice guidelines recommend an invasive approach for managing non\u0026ndash;ST-elevation acute coronary syndromes, which includes routine cardiac catheterization and revascularization upon admission.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e However, there is a lack of specific invasive treatment guidelines and evidence-based recommendations for older patients with acute coronary syndromes, primarily due to their underrepresentation in clinical trials.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e This gap ultimately results in a significant portion of this patient population being deprived of potentially beneficial invasive treatments.\u003c/p\u003e \u003cp\u003ePrevious meta-analysis has explored the differences in myocardial infarction outcomes between invasive and conservative treatments in elderly patients with NSTEACS, and the composite results of all-cause mortality and myocardial infarction were negative.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e However, a recent large randomized controlled trial, which included a significant amount of additional data, demonstrated that invasive strategies did not lead to a reduction in the overall incidence of myocardial infarction or all-cause mortality.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e This finding contradicts the conclusions of earlier meta-analyses and may reflect the relatively small sample sizes of the studies included in those analyses. Consequently, there is a pressing need for new analyses of these critical data.\u003c/p\u003e \u003cp\u003eThe aim of this meta-analysis is to utilize all the recent randomized controlled trials to investigate the comparative benefits of conventional invasive strategies versus conservative strategies in the elderly, particularly in relation to patients with elderly myocardial infarction. The ultimate objective is to provide robust, evidence-based recommendations to inform clinical decision-making, with the aim of improving outcomes and prognosis for this high-risk patient population.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eProtocol and guidance\u003c/h2\u003e \u003cp\u003eTh This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Furthermore, prior to commencing the study, we prospectively registered the research protocol at PROSPERO under registration number CRD42024608953. This procedure was implemented to enhance transparency and ensure compliance with established evidence-based research standards.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSearch strategy and selection criteria\u003c/h3\u003e\n\u003cp\u003eStudies were eligible for inclusion if they 1) focused on non-ST elevation acute coronary syndromes (NSTEACS), defined by clinical symptoms suggestive of acute myocardial ischemia, the absence of persistent ST-segment elevation, and elevated troponin levels, as confirmed by the local laboratory\u0026rsquo;s assay; 2) involved participants aged 70 years or older; 3) were randomized controlled trials; 4) included an intervention group that received invasive treatments (such as coronary angiography and revascularization); and 5) reported at least one of the predefined key outcomes, including myocardial infarction or mortality.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was 1-year all-cause mortality, while the secondary outcome focused on myocardial infarction (MI). All included studies defined MI as the occurrence of new cardiac symptoms accompanied by troponin levels exceeding the 99th percentile.\u003c/p\u003e\n\u003ch3\u003eData sources and search strategy\u003c/h3\u003e\n\u003cp\u003eWe searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from inception until October, 2024. The search terms used were \u0026ldquo;Non-ST Elevated Myocardial Infarction,\u0026rdquo; \u0026ldquo;Angioplasty, Balloon, Coronary,\u0026rdquo; \u0026ldquo;Conservative Treatment,\u0026rdquo; and \u0026ldquo;Aged.\u0026rdquo; There were no limitations based on language. Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e in the Data Supplement outlines the comprehensive search terms employed in each database searched.\u003c/p\u003e\n\u003ch3\u003eInclusion criteria\u003c/h3\u003e\n\u003cp\u003eTwo reviewers (SF and XY) independently screened all titles and abstracts retrieved from the systematic search. To ensure the accuracy of the data, a third reviewer (YZ) was consulted to resolve any discrepancies. Any disagreements between reviewers were addressed through discussion or, if necessary, adjudicated by the third reviewer (YZ).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eData extraction\u003c/h2\u003e \u003cp\u003eTo ensure the integrity and reliability of the study selection process, two independent reviewers (SF and XY) conducted a thorough screening of all titles and abstracts identified during the systematic search. Any potential discrepancies or uncertainties in the data were addressed by a third reviewer (YZ), who was responsible for verifying and resolving any inconsistencies. In cases of disagreement between the two primary reviewers, the third reviewer (YZ) intervened to adjudicate the issue through discussion and consensus, ensuring that the final selection adhered to the predefined inclusion criteria.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAssessment of the risk of bias\u003c/h3\u003e\n\u003cp\u003eTwo reviewers (SF and XY) independently evaluated the risk of bias in the included trials using the Cochrane Risk of Bias-2 tool, assessing five key domains: bias due to the randomization process, deviations from intended interventions, missing outcome data, outcome measurement, and selection of reported results.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e For each domain, a study-level score was assigned, categorizing the risk of bias as low, high, or unclear. Any disagreements between the two primary reviewers were resolved through discussion. In cases where consensus could not be reached, a final decision was made by a third reviewer (YZ), ensuring a thorough and impartial evaluation of the risk of bias across all trials.\u003c/p\u003e\n\u003ch3\u003eConfidence of evidence\u003c/h3\u003e\n\u003cp\u003eThe quality of evidence for both the primary and secondary outcomes was independently evaluated by two authors (SF and XY) using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This assessment helped to determine the strength and reliability of the evidence supporting each outcome.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e This rigorous assessment process involved categorizing the quality of evidence as high, moderate, low, or very low. Various factors were taken into consideration during this evaluation, including the study designs, the potential risk of bias in their methodologies, inconsistencies in the results, the imprecision of effect estimates, and the indirectness of the findings relative to the clinical questions posed.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003e Statistical analysis was performed using Review Manager (version 5.4, The Cochrane Collaboration). For binary outcomes, relative risks with 95% confidence intervals (CI) were calculated. For continuous data, we computed the mean difference (MD) with 95% CI. Heterogeneity across studies was assessed using Cochrane\u0026rsquo;s Q test and Higgins\u0026rsquo; I\u0026sup2; statistic, with Q values set at a significance level of 10% (p\u0026thinsp;\u0026lt;\u0026thinsp;0.1) and I\u0026sup2; values greater than 50% indicating substantial heterogeneity. To ensure the robustness of the results, random-effects models were applied for all outcomes. A two-sided p-value of less than 0.05 was considered statistically significant. Forest plots were generated to visualize the effect sizes and combined estimates. All analyses were conducted using two-tailed tests, with a significance threshold of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePublication bias\u003c/h2\u003e \u003cp\u003eIf the meta-analysis included 10 or more studies, a funnel plot would be generated, and quantitative assessments would be conducted using Egger\u0026rsquo;s\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e and Begg's\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e tests to evaluate potential biases related to small-study effects.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup analysis\u003c/h2\u003e \u003cp\u003eSubgroup analysis of the primary outcome was performed according to age groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity analysis\u003c/h2\u003e \u003cp\u003eIn the sensitivity analysis, we applied a fixed-effect model and excluded studies contributing less than 5% to the overall weight to evaluate their potential influence on the pooled relative risk (RR) for mortality.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOur initial search strategy retrieved 366 records. After removing duplicates, 227 unique records remained. We then conducted a thorough review of titles, abstracts, and full-texts, ultimately identifying 7 trials\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan additionalcitationids=\"CR16 CR17 CR18 CR19\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e that met the inclusion criteria for this systematic review. (Fig.\u0026nbsp;1)\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;1 summarizes the characteristics of the trials included in this study. These trials were published between 2012 and 2024, with sample sizes ranging from 106 to 1,518 patients. The supplementary data includes Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e, which includes an evaluation of the risk of bias. The assessment revealed that the majority of studies exhibited a low risk of bias, particularly regarding random sequence generation and allocation concealment. However, the seven studies included in the analysis showed a high risk of bias in terms of blinding of both participants and personnel, as well as outcome assessment, which is probably due to the distinct differences between invasive and conservative treatments, making blinding operations challenging. Through GRADE assessment, the evidence quality for the primary outcome was rated as moderate, while the evidence quality for the secondary outcome of myocardial infarction was rated as moderate (table S2 in the Data Supplement).\u003c/p\u003e \u003cp\u003eAll seven trials reported data on the primary outcome, and six also specified data on myocardial infarction. After a one-year follow-up, we did not find any difference in all-cause mortality between the invasive treatment group and the conservative treatment group (RR 1.05, 95%CI 0.94 to 1.18, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%) (Fig.\u0026nbsp;2), but invasive treatment could reduce the risk of myocardial infarction (RR 0.74, 95%CI 0.57 to 0.95, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;38%) (Fig.\u0026nbsp;3).\u003c/p\u003e \u003cp\u003eThe sensitivity analysis indicated that the use of a fixed-effect model instead of a random-effects model (RR 0.74, 95% CI 0.62 to 0.88) still did not show a difference in all-cause mortality for NSTEACS patients (Table S3 in Date Supplement). Additionally, when studies contributing less than 5% to the overall weight were excluded (RR 1.04, 95%CI 0.90 to 1.19, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;7%), the primary results remained unchanged (Table S3 in Date Supplement).\u003c/p\u003e \u003cp\u003eThe subgroup results for the primary outcome in NSTEACS patients suggest that the age factor (\u0026gt;\u0026thinsp;70 vs. \u0026gt;75 vs. \u0026gt;80, P for interaction\u0026thinsp;=\u0026thinsp;0.36) (Figure S2 in the Data Supplement).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis analysis is based on seven randomized controlled trials, which included 2997 patients with Non\u0026ndash;ST-segment elevation acute coronary syndrome. In our meta-analysis, we revealed that an invasive treatment strategy compared to a conservative strategy of the best available medical therapy, does not lead to a reduction in all-cause mortality. However, there is convincing evidence that invasive treatment lowers the risk of MI.\u003c/p\u003e \u003cp\u003eA previous meta-analysis also examined this topic.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e It concluded that there were differences in the outcomes of myocardial infarction (hazard ratio 0.62, 95% CI 0.44 to 0.87), but no difference was observed in all-cause mortality at one year (hazard ratio 1.03, 95% CI 0.69 to 1.53). However, this result contradicts the latest findings of a randomized controlled trial with a larger sample size that was recently released, which indicated that invasive strategies did not lower the overall incidence of myocardial infarction or all-cause mortality.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e In comparison, we included a larger dataset comprising 2,997 patients, which is 1,518 more than in previous meta-analyses. Our main advantage lies in the greater accuracy of our results, with a narrower confidence interval, such as for all-cause mortality (95% CI 0.98 to 1.18). Globally, ischemic intervals remained largely unaffected, thereby validating the robustness of the study's findings. Cardiovascular disease is the leading cause of death worldwide, with a disproportionately higher mortality burden among older adults. Notably, individuals over the age of 75 represent the strongest negative predictor for receiving routine invasive care, with frail patients or those with comorbidities are less likely to undergo coronary angiography.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Guideline recommendations for managing ACS are often derived from studies that exclude older patients. More contemporary trials have frequently been underpowered and have produced inconsistent findings regarding this population. Additionally, the potential impact of age and underlying diseases on the degree of physical frailty in patients remains inadequately understood.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Evidence regarding the impact of frailty and comorbidities on management decisions is scarce. Therefore, clinical guidelines and evidence-based practices should inform the decision-making process, carefully considering the potential benefits and risks associated with each strategy.\u003c/p\u003e \u003cp\u003eThere are several limitations that need to be considered. Firstly, inconsistencies in the inclusion criteria, particularly the definition of age for elderly patients, have introduced variability to the research field. The variations in age within the studies may have further contributed to heterogeneity, and these parameters should be standardized in future studies. Second, there was a notable lack of frailty assessments in the studies, with only the MOSCA-FRAIL trial providing relevant data. Frailty is commonly observed in elderly patients with NSTEACS and may have a substantial impact on the potential benefits of coronary angiography and revascularization procedures. Third, the Coronavirus Disease 2019 (COVID-19) pandemic may have influenced the outcomes of several trials.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e During this period, many patients, particularly those in the conservative treatment group, were understandably more hesitant to seek hospital care due to the heightened risk of COVID-19 infection. This reluctance was compounded by global lockdowns, social distancing measures, and concerns about overwhelming healthcare systems. As a result, patients may have postponed or avoided necessary medical interventions, potentially impacting their health outcomes. Fourth, further subgroup analyses were not feasible. Although we conducted a subgroup analysis based on age, the lack of detailed data in the included studies limited the exploration of other subgroups. For example, information on comorbidities or disease type was not consistently reported, preventing a deeper analysis of how these factors might influence treatment outcomes.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn the elderly with Non\u0026ndash;ST-segment elevation myocardial infarction, invasive treatment did not improve all-cause mortality at 1-year follow-up compared to conservative management. However, it significantly reduced the risk of myocardial infarction.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNSTEACS non-ST-segment elevation acute coronary syndrome\u003c/p\u003e\n\u003cp\u003eMI myocardial infarction\u003c/p\u003e\n\u003cp\u003eCOVID-19 Coronavirus Disease 2019\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGRADE Grading of Recommendation, Assessment, Development and Evaluation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analysis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCI Confidence intervals\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRR Relative risk\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOR Odds ratio\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMD Mean difference\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003enone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy concept: YZ. Design: All authors. Acquisition, analysis, or interpretation of data: SF, XY, JW, PW, JH, KL, QY, JH, XL, XY, ZX, XL and YR. Statistical analysis: SF and XY. Drafting of the manuscript: SF, XY and JW. Critical revision of the manuscript for important intellectual content: All authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe acknowledge the use of GPT-based AI for language refinement in the manuscript preparation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll relevant data are within the manuscript and its Supporting Information files. And the data used in this study are obtained from publicly available sources.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGlobal national age-sex specific mortality for 264 causes of death, 1980\u0026ndash;2016: a systematic analysis for the Global Burden of Disease Study 2016. \u003cem\u003eLancet\u003c/em\u003e \u003cb\u003e390\u003c/b\u003e, 1151\u0026ndash;1210. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/s0140-6736(17)32152-9\u003c/span\u003e\u003cspan address=\"10.1016/s0140-6736(17)32152-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBatty, J. et al. 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Frailty is independently associated with short-term outcomes for elderly patients with non-ST-segment elevation myocardial infarction. \u003cem\u003eCirculation\u003c/em\u003e \u003cb\u003e124\u003c/b\u003e, 2397\u0026ndash;2404. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1161/circulationaha.111.025452\u003c/span\u003e\u003cspan address=\"10.1161/circulationaha.111.025452\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2011).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eCharacteristics of studies included in the meta-analysis\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTrial\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCountry\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Participants\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 27px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian Timing of Angiography in the invasive group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCrossover from Conservative to PCI or CABG (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian no. of days from admission to randomization\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003efrom admission to angiography\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003efrom randomization to angiography\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eStefano Savonitto et al., 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003eItaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNSTEACS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026ge; 75 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e1 day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNicolai Tegn et al., 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003eNorway\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNSTEACS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026ge; 80 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e457\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 27px;\"\u003e\n \u003cp\u003e3 days (Not specifically stated)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eJuan Sanchis et al., 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003eSpain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNSTEMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026ge; 70 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eGeir Hirlekar et al., 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003eSweden\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNSTEACS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026ge; 80 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e186\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eAdam De Belder et al., 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003eUnited Kingdom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNSTEMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026ge; 80 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e2 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eJuan Sanchis et al., 2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003eSpain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNSTEMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026ge; 70 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e167\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eV.Kunadian et al.，2024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003eUnited Kingdom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNSTEMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026ge; 75 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e1518\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e5 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNSTEACS：non\u0026ndash;ST-segment elevation acute coronary syndromes, NSTEMI：non-ST-elevation myocardial infarction\u003c/p\u003e\n\u003cp\u003ePCI：percutaneous coronary intervention, CABG：coronary artery bypass grafting,\u0026nbsp;NR: not reported\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"non-ST-segment elevation acute coronary syndrome, myocardial infarction, Meta-analysis","lastPublishedDoi":"10.21203/rs.3.rs-5842406/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5842406/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe benefits of conservative treatment versus invasive strategies for elderly patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) remain ambiguous. Consequently, this systematic review and meta-analysis aimed to assess and compare the effects of invasive versus conservative treatment strategies in elderly patients diagnosed with NSTEACS.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to October 2024 to identify RCTs comparing invasive versus conservative management in elderly patients with non-ST-elevation acute coronary syndrome. The primary outcome was all-cause mortality at 1 year, with secondary outcome including myocardial infarction (MI).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSeven trials (2997 patients) reported primary outcome data, with six also providing data on myocardial infarction. At 1-year follow-up, there was no difference in all-cause mortality between the invasive treatment group and the conservative treatment group (RR 1.05, 95%CI 0.94 to 1.18, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%) After a one-year follow-up, but invasive treatment reduce the risk of myocardial infarction (RR 0.74, 95%CI 0.57 to 0.95, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;38%).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn the elderly with Non\u0026ndash;ST-segment elevation myocardial infarction, invasive treatment did not improve all-cause mortality at 1-year follow-up compared to conservative management. However, it was found to significantly lower the risk of myocardial infarction.\u003c/p\u003e","manuscriptTitle":"Invasive versus conservative management of older patients with non-ST- elevation acute coronary syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-05 11:44:39","doi":"10.21203/rs.3.rs-5842406/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"426133ec-9e39-418d-a80b-3f6ccbc64fdd","owner":[],"postedDate":"February 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":43842802,"name":"Health sciences/Medical research/Outcomes research"},{"id":43842803,"name":"Health sciences/Cardiology/Interventional cardiology"}],"tags":[],"updatedAt":"2025-05-20T07:23:44+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-05 11:44:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5842406","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5842406","identity":"rs-5842406","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}