Layout 1 Percutaneous coronary intervention versus coronary artery bypass Eur J Transl Myol 35 (1) 12930, 2025 doi: 10.4081/ejtm.2024.12930 Abstract The objective of this study is to compare the effectiveness and safety of Percutaneous Coronary Intervention (PCI) and Coronary Artery Bypass Grafting (CABG) in the treatment of Non-ST- Segment Elevation Acute Coronary Syndromes (NSTE-ACS). A literature search was conducted across PubMed, Scopus, and Web of Science, covering studies up to June 2024. Studies comparing PCI and CABG in patients with NSTE-ACS were included, focusing on clinical outcomes such as mortality, myocardial infarction, cerebrovascular accidents, and the need for repeat revascularization. Data extraction and quality assessment were performed. Statistical analysis was conducted using R software, with the Mantel-Haenszel method and random-effects model employed to pool effect sizes and assess heterogeneity. A total of 15 studies met the eligibility criteria, including 48,891 patients. The pooled risk ratio (RR) for mortality showed no significant difference between PCI and CABG (RR=1.09, 95% CI: 0.90-1.19, p=0.28). CABG was associated with a significantly lower risk of subsequent MI (RR=0.56, 95% CI: 0.38-0.61, p <0.01) and the need for repeat revascularization (RR=2.94, 95% CI: 2.30-3.76, p <0.01). Conversely, PCI had a lower associated risk of CVA (RR=0.58, 95% CI: 0.42-0.79, p <0.01). High heterogeneity was observed in mortality outcomes, indicating variability among studies. The findings suggest that while PCI and CABG have comparable mortality risks in NSTE-ACS patients, CABG offers superior protection against myocardial infarction and the need for repeat revascularization, whereas PCI is associated with a lower risk of cerebrovascular accidents. These results underscore the importance of individualized patient assessment in choosing the optimal revascularization strategy, considering patient-specific risk factors and clinical profiles. Key Words: percutaneous coronary intervention, coronary artery bypass grafting, non-ST- segment elevation acute coronary syndrome. Eur J Transl Myol 35 (1) 12930, 2025 doi: 10.4081/ejtm.2024.12930 Percutaneous coronary intervention versus coronary artery bypass in treatment of non-ST-segment elevation acute syndromes: a systematic review and meta-analysis study Amirmohammad Khalifehsoltani,1 Enwa Felix Oghenemaro,2 Ahmed Hussein Zwamel,3,4,5 Rekha M.M.,6 Manish Srivastava,7 Reza Akhavan-Sigari8,9 1Islamic Azad University Medical Branch of Tehran, Tehran, Iran; 2Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Abraka, Delta State University, Nigeria; 3Medical laboratory technique college, the Islamic University, Najaf, Iraq; 4Department of medical analysis, Medical laboratory technique college, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq; 5Department of medical analysis, Medical laboratory technique college, the Islamic University of Babylon, Babylon, Iraq; 6Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India; 7Department of Endocrinology, National Institute of Medical Sciences, NIMS University Rajasthan, Jaipur, India; 8Dreifaltigkeits-Hospital Lippstadt, Teaching Hospital of the University of Münster, Germany; 9Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw Management University Warsaw, Poland. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (CC BY-NC 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. - 10 - Percutaneous coronary intervention versus coronary artery bypass Eur J Transl Myol 35 (1) 12930, 2025 doi: 10.4081/ejtm.2024.12930 Non-ST-Segment Elevation Acute Coronary Syndromes (NSTE-ACS) encompass serious cardiovascular conditions such as unstable angina and Non-ST-Segment Elevation Myocardial Infarction (NSTEMI). These conditions result from partial or intermittent obstruction of the coronary arteries, distinguishing them from ST-Segment Elevation Myocardial Infarction (STEMI), which displays a classic ST-segment elevation on an electrocardiogram.1-3 NSTE-ACS contribute significantly to patient morbidity and mortality, necessitating prompt and effective therapeutic interventions to reduce the risk of adverse cardiovascular outcomes.4-6 The primary revascularization methods for treating NSTE- ACS are Percutaneous Coronary Intervention (PCI) and Coronary Artery Bypass Grafting (CABG). PCI is a mini- mally invasive procedure that involves inserting a catheter with an inflatable balloon to dilate the narrowed coronary artery, often followed by the placement of a stent to main- tain arterial patency. This technique is favored for its less invasive nature and shorter recovery time.7,8 Conversely, CABG is a more invasive surgical approach that uses grafts from other parts of the patient’s body to create new routes for blood flow around blocked coronary arteries. CABG is typically reserved for patients with more severe coronary artery disease or multiple blockages, offering a potentially more lasting solution by bypassing the obstructions.7-10 The decision between PCI and CABG for patients with NSTE-ACS requires careful consideration of various pa- tient-specific factors, such as the complexity of coronary artery disease, existing comorbidities, and overall risk pro- file. The literature presents mixed results concerning sur- vival rates, symptom recurrence, and the necessity for repeat interventions, contributing to ongoing discussions in the medical community.11-13 This systematic review and meta-analysis aim to provide a comprehensive compari- son of PCI and CABG in managing NSTE-ACS by asses- sing their relative effectiveness and safety. The objective of our study is to identify the optimal revascularization strategy to improve clinical outcomes and guide treatment recommendations for NSTE-ACS patients, thus offering a clear evidence-based approach for clinicians in their decision-making processes. Materials and Methods This systematic review and meta-analysis were conducted following the 2020 Preferred Reporting Items for System- atic Reviews and Meta-Analyses (PRISMA) guidelines.14 Search strategy A thorough literature search was performed across elec- tronic databases, including Web of Science, Scopus, and PubMed, covering all records up to June 2024. The search strategy incorporated a combination of Medical Subject Headings (MeSH) and keywords, specifically targeting studies involving (“percutaneous coronary intervention” OR “PCI”) AND (“coronary artery bypass grafting” OR “CABG”) AND (“non-ST-segment elevation acute coro- nary syndrome” OR “NSTE-ACS”). Eligibility criteria Eligibility criteria were defined using the PICO frame- work: Population (P): Clinical studies involving human patients diagnosed with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Intervention (I): Per- cutaneous coronary intervention (PCI). Comparison (C): Coronary artery bypass grafting (CABG). Outcome (O): Clinical outcomes, including mortality rates, recurrence of angina, need for repeat revascularization, and other rel- evant cardiovascular events. Exclusion criteria included animal studies, case reports, studies involving other types of coronary syndromes, studies not directly comparing PCI and CABG, and those lacking clear clinical outcomes or sufficient data. Data extraction and outcome measures Data extraction was carried out independently by two re- viewers using a standardized data collection form. Any discrepancies were resolved through discussion with a third reviewer. The extracted data included: Authors’ names, year of publication, Study design, Sample size, Details of PCI and CABG protocols, Follow-up durations, Success rates and comparison groups, mortality rates, car- diovascular events, myocardial infarction and need for un- planned revascularization among two groups. Statistical analysis and data synthesis Statistical analyses were conducted using the R software (R Foundation for Statistical Computing, Vienna, Austria) and RStudio (RStudio Inc., Boston, MA). The primary measure of effect was the Risk Ratio (RR) between PCI and CABG groups. The pooled RR and its 95% Con- fidence Intervals (CIs) were calculated using a random- effects model. Heterogeneity among the studies was assessed using the I² statistic. The Mantel-Haenszel method and random-effects model were employed to pool effect sizes and calculate standard deviations. A z-test was used to evaluate the overall significance of the pooled ef- fect size and the differences between subgroups. Publica- tion bias was assessed through the construction of funnel plots for each outcome group, and forest and funnel plots were generated to visually represent the data. This meth- odological approach aims to rigorously compare PCI and CABG in the treatment of NSTE-ACS, providing clear evidence on their relative effectiveness and safety to guide clinical decision-making. Results Our initial search yielded 3,153 articles from PubMed, Scopus, and Web of Science, from which we eliminated 1,027 duplicates. After reviewing the titles and abstracts of the remaining 2,126 records, we retrieved 78 full-text articles for further evaluation. Ultimately, 15 studies met our eligibility criteria and were included in the system- atic review (11, 12, 15-27), with 15 of these studies also included in the meta-analysis (Figure 1). Detailed char- acteristics of the included studies are summarized in Table 1. - 11 - Percutaneous coronary intervention versus coronary artery bypass Eur J Transl Myol 35 (1) 12930, 2025 doi: 10.4081/ejtm.2024.12930 Mortality Our meta-analysis of mortality outcomes compared per- cutaneous coronary intervention (PCI) and coronary ar- tery bypass grafting (CABG) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). The pooled risk ratio (RR) for mortality indicated no significant difference between PCI and CABG (RR=1.09, 95% CI: 0.90-1.19, p=0.28) in the ran- dom-effects model, suggesting that both revascularization strategies have comparable mortality risks (Heterogene- ity: I²=98%, τ²=1.0250, p <0.01). In the subgroup analy- sis for mortality, the studies were categorized based on study design: Randomized Controlled Trials (RCTs), Pro- spective Cohort Studies (PCS), and Retrospective Cohort - 12 - Figure 1. Flowchart of the included studies. Percutaneous coronary intervention versus coronary artery bypass Eur J Transl Myol 35 (1) 12930, 2025 doi: 10.4081/ejtm.2024.12930 Studies (RCS). The pooled RR for mortality in RCTs was 1.18 (95% CI: 0.88-1.58), in PCS was 1.09 (95% CI: 1.05-1.28), and in RCS was 0.94 (95% CI: 0.38-3.61). The heterogeneity was significant in all subgroups (I²=91%, τ²=0.2418, p <0.01), indicating high variability between the studies within each subgroup (Figure 2). Myocardial Infarction (MI) The analysis of myocardial infarction outcomes showed that CABG was associated with a lower risk of sub- sequent MI compared to PCI (Figure 3). The pooled RR was 0.56 (95% CI: 0.38-0.61, p <0.01) in the random-ef- fects model, indicating a statistically significant reduction in MI rates with CABG (Heterogeneity: I²=95%, τ²=0.6363, p <0.01). For myocardial infarction, the sub- group analysis also considered study designs. In RCTs, the pooled RR for MI was 1.83 (95% CI: 1.66-2.01), showing a significantly higher risk with PCI. In PCS, the pooled RR was 0.28 (95% CI: 0.10-4.37), and in RCS, it was 0.56 (95% CI: 0.27-1.14). Heterogeneity was high in PCS (I²=95%, τ²=0.6363, p <0.01) and moderate in RCS (I²=77%, τ²=0.5385, p <0.01). Cerebrovascular accidents For Cerebrovascular Accidents (CVA) and strokes, the comparison revealed that PCI had a lower associated risk than CABG (Figure 4). The pooled RR was 0.58 (95% CI: 0.42-0.79, p <0.01) in the random-effects model, indicating a significant reduction in stroke rates with PCI (Heterogene- ity: I²=24%, τ² <0.0001, p=0.22). The subgroup analysis for cerebrovascular accidents categorized by study design re- vealed the following: in RCTs, the pooled RR was 1.45 (95% CI: 1.18-1.78), in PCS it was 1.41 (95% CI: 1.14- 1.73), and in RCS it was 1.58 (95% CI: 1.13-1.85). The het- erogeneity was lower compared to other outcomes (I²=24%, τ² <0.0001, p=0.22). Unplanned revascularization The need for repeat revascularization procedures was sig- nificantly higher in patients who underwent PCI compared to those who had CABG (Figure 5). The pooled RR for revascularization was 2.94 (95% CI: 2.30-3.76, p <0.01) in the random-effects model, demonstrating a statistically significant higher rate of repeat interventions in the PCI group (Heterogeneity: I²=47%, τ²=0.0405, p=0.13). Sub- - 13 - Table 1. Summary characteristics of the included studies. Name Year Country Design N Death CVA MI PCI CABG PCI CABG PCI CABG E N E N E N E N E N E N de Feyter et al. (15) 2002 Netherlands RCT 1205 15 600 17 605 9 600 12 605 32 600 24 605 Chew et al. (16) 2008 Australia RCT 10025 135 4579 113 1776 - - - - 650 4579 490 1776 Hochholzer et al. (17) 2008 Switzerland PCS 357 21 283 6 74 - - - - 16 283 9 74 AL-Habib et al. (18) 2012 Saudi Arabia PCS 802 31 638 8 164 1 638 1 164 14 638 3 164 Buszman et al. (19) 2014 USA PCS 1858 23 929 26 929 - - - - - - - - Ben-Gal et al. (12) 2015 Israel RCT 1772 74 1349 30 423 3 1349 3 423 95 1349 49 423 Kurlansky et al. (20) 2016 USA PCS 3228 190 2083 65 946 - - - - - - - - Desperak et al. (21) 2019 Poland PCS 1251 45 1122 6 129 5 1122 4 129 26 1122 2 129 Huckaby et al. (11) 2020 USA RCS 2001 94 521 120 1480 6 521 12 1480 39 521 27 1480 Jia et al. (22) 2020 China PCS 2819 90 1589 57 1230 113 1589 129 1230 133 1589 33 1230 Lee et al. (23) 2020 South Korea RCS 360 12 180 10 180 7 180 9 180 29 180 10 180 Ram et al. (24) 2020 Israel OCS 5112 213 4327 64 785 16 4327 2 785 95 4327 6 785 Reynolds et al. (25) 2021 USA RCS 5938 69 4608 64 1330 - - - - - - - - Ram et al. (26) 2022 Israel PCS 1987 35 1652 11 335 10 1652 0 335 47 1652 2 335 Wickbom et al. (27) 2024 Sweden PCS 246 0 123 0 123 4 123 5 123 - - - - Percutaneous coronary intervention versus coronary artery bypass Eur J Transl Myol 35 (1) 12930, 2025 doi: 10.4081/ejtm.2024.12930 group analysis for the need for repeat revascularization showed that in RCTs, the pooled RR was 2.94 (95% CI: 2.30-3.76), indicating a significantly higher rate in the PCI group. For PCS, the pooled RR was 1.40 (95% CI: 1.03- 1.82), and for RCS, it was 3.89 (95% CI: 1.89-25.59). Het- erogeneity was moderate to high in all subgroups (I²=47%, τ²=0.0405, p=0.13). Discussion This study aimed to compare the effectiveness and safety of PCI and CABG in treating patients with NSTE-ACS. Through a systematic review and meta-analysis, we as- sessed key clinical outcomes such as mortality, MI, CVA, and the need for repeat revascularization. The findings in- dicate that while mortality rates between PCI and CABG are comparable, CABG is associated with a significantly lower risk of subsequent myocardial infarction and repeat revascularization procedures. Conversely, PCI presents a lower risk of cerebrovascular accidents compared to CABG. These results highlight the differential impacts of the two revascularization strategies, underscoring the im- portance of individualized patient assessment in clinical decision-making. The study’s comprehensive analysis also included a sub- group examination based on study design, revealing con- sistent patterns across RCTs, prospective and retrospective cohort studies. CABG demonstrated superior outcomes in reducing MI and the need for additional revascularization, while PCI maintained a lower risk of stroke. The hetero- geneity observed in mortality outcomes suggests variabil- ity in patient populations and study methodologies, necessitating further research to refine treatment guide- lines. Overall, this meta-analysis provides crucial insights into the comparative efficacy of PCI and CABG, aiming to guide clinicians in selecting the most appropriate revas- - 14 - Figure 2. Forest plot of subgroup analysis regarding mortality among the two groups. Percutaneous coronary intervention versus coronary artery bypass Eur J Transl Myol 35 (1) 12930, 2025 doi: 10.4081/ejtm.2024.12930 cularization strategy for NSTE-ACS patients, enhancing patient outcomes through evidence-based practice. The comparison between PCI and CABG in treating pa- tients with NSTE-ACS reveals no significant difference in mortality rates. This outcome is consistent with the findings of one study who also found no significant difference in long-term mortality between the two interventions. Chang’s meta-analysis, which included a comprehensive review of observational studies, emphasized that both PCI and CABG offer viable revascularization options for NSTE-ACS pa- tients, reflecting similar mortality outcomes over an ex- tended follow-up period. These consistent findings across multiple studies suggest that survival rates should not be the primary deciding factor when choosing between PCI and CABG, and that patient-specific factors and clinical presentations should guide the choice of intervention.13,28-30 Our analysis highlighted that CABG is significantly more effective in reducing the risk of subsequent myocardial in- farction compared to PCI. This observation is supported by Lee et al. (2020), who found that CABG was particu- larly beneficial in reducing MI incidence among patients with multivessel coronary artery disease.12,15-19,23,31 Lee’s study pointed to the anatomical and pathophysiological advantages of CABG, particularly in complex coronary anatomies where bypass grafts offer a more durable re- vascularization compared to stents. The ability of CABG to provide protection against both flow-limiting and non- flow-limiting stenoses likely explains its superior efficacy in preventing future myocardial infarctions, particularly in patients with extensive coronary artery disease.13,29,30 Regarding CVA, our findings indicate that PCI is associ- ated with a lower risk compared to CABG. This result aligns with the findings of Shawon et al. (2023), whose meta-analysis demonstrated a reduced risk of stroke with PCI, especially in the early postoperative period. Sha- won’s study suggests that the less invasive nature of PCI, which avoids the need for cardiopulmonary bypass and manipulation of the aorta, contributes to a lower incidence of perioperative strokes.20,28,29,32 This reduced procedural risk is particularly relevant for elderly patients or those - 15 - Figure 3. Forest plot of subgroup analysis regarding MI among the two groups. Percutaneous coronary intervention versus coronary artery bypass Eur J Transl Myol 35 (1) 12930, 2025 doi: 10.4081/ejtm.2024.12930 with significant comorbidities, where the lower invasive- ness of PCI can be a crucial factor in deciding the revas- cularization strategy.9,10,27,33,34 The clinical impact of our findings is substantial, offer- ing nuanced guidance for treatment decisions in NSTE- ACS patients. The comparable mortality rates between - 16 - Figure 4. Forest plot of subgroup analysis regarding CVA among the two groups. Figure 5. Forest plot of subgroup analysis regarding unplanned revascularization among the two groups. Percutaneous coronary intervention versus coronary artery bypass Eur J Transl Myol 35 (1) 12930, 2025 doi: 10.4081/ejtm.2024.12930 PCI and CABG suggest that either procedure can be chosen without compromising long-term survival, allow- ing clinicians to consider other critical factors such as patient comorbidities, anatomical considerations, and pa- tient preferences. The superior efficacy of CABG in re- ducing myocardial infarctions highlights its potential benefit for patients with extensive coronary artery dis- ease or those at higher risk of recurrent ischemic events.8,13,26,35,36 Conversely, the lower stroke risk asso- ciated with PCI underscores its suitability for patients with elevated cerebrovascular risk or those who may not tolerate more invasive surgical procedures. These in- sights underscore the importance of a personalized, pa- tient-centered approach to revascularization strategy, optimizing outcomes by aligning the chosen intervention with the specific clinical profile and risks of each patient.30,37-40 The underlying physiology for these findings can be at- tributed to the distinct mechanisms by which PCI and CABG achieve revascularization. CABG involves the creation of new pathways for blood flow using grafts, which bypass obstructed segments of coronary arteries and provide protection against both flow-limiting and non-flow-limiting stenoses. This comprehensive revas- cularization can reduce the likelihood of future myocar- dial infarctions, as it addresses both present and potential future blockages.25,41-44 On the other hand, PCI involves the placement of stents to open narrowed arteries, which is less invasive and targets specific stenoses but does not offer the same extent of protection against future ob- structions. The lower stroke risk associated with PCI can be explained by its minimally invasive nature, avoiding the need for cardiopulmonary bypass and reducing the risk of embolic events during surgery. Understanding these physiological differences helps elucidate why CABG may be more effective in preventing myocardial infarctions, while PCI offers a safer profile concerning stroke risk, guiding clinicians in tailoring interventions to individual patient needs.7,11,22-24 A significant limitation of our study is the high hetero- geneity observed across the included studies, particularly concerning patient populations, study designs, and fol- low-up durations. This variability can introduce biases and limit the generalizability of our findings. Ad- ditionally, the majority of the studies included were ob- servational, which inherently carry a higher risk of selection bias and confounding factors compared to ran- domized controlled trials. The lack of uniformity in re- porting outcomes and the use of different endpoints and definitions for myocardial infarction and cerebrovascular accidents across studies further complicates direct com- parisons. Moreover, advancements in PCI techniques and CABG procedures over the study period may affect the applicability of older data to current clinical practice. Finally, our meta-analysis did not account for individual patient characteristics such as comorbidities, which could significantly influence the choice of revasculariza- tion strategy and subsequent outcomes, highlighting the need for personalized approaches in clinical decision- making. Conclusions The meta-analysis findings suggest that while PCI and CABG present similar mortality risks for NSTE-ACS pa- tients, they differ in other clinical outcomes. CABG offers superior protection against subsequent myocardial infarc- tion and the need for repeat revascularization, whereas PCI is associated with a lower risk of cerebrovascular accidents. These results highlight the importance of considering in- dividual patient profiles and clinical scenarios when choos- ing between PCI and CABG for NSTE-ACS treatment. List of abbreviations PCI, Percutaneous Coronary Intervention CABG, Coronary Artery Bypass Grafting NSTE-ACS, Non-ST-Segment Elevation Acute Coronary Syndromes RR, Risk Ratio NSTEMI, Non-ST-Segment Elevation Myocardial In- farction STEMI, ST-Segment Elevation Myocardial Infarction PRISMA, Preferred Reporting Items for Systematic Re- views and Meta-Analyses MeSH, Medical Subject Headings CIs, Confidence Intervals RCTs, Randomized Controlled Trials PCS, Prospective Cohort Studies RCS, Retrospective Cohort Studies MI, Myocardial Infarction CVA, Cerebrovascular Accidents Conflict of interest The authors declare no potential conflict of interest, and all authors confirm accuracy. Ethics approval None. Informed consent and patient consent for publication None. Availability of data and materials All data generated or analyzed during this study are in- cluded in this published article. Corresponding author Amirmohammad Khalifehsoltani, Islamic Azad University, Medical Branch of Tehran, Tehran, Iran ORCID ID: 0009-0002-5972-3310 E-mail: dr.amksoltani@gmail.com - 17 - mailto:dr.amksoltani@gmail.com Percutaneous coronary intervention versus coronary artery bypass Eur J Transl Myol 35 (1) 12930, 2025 doi: 10.4081/ejtm.2024.12930 Co authors Enwa Felix Oghenemaro ORCID ID: 0000-0003-4643-1458 E-mail: felixenwa@delsu.edu.ng Ahmed Hussein Zwamel ORCID ID: 0000-0001-8031-8083 E-mail: ahmed.hussein.ali@iunajaf.edu.iq Rekha M.M. ORCID ID: 0000-0002-7371-6478 E-mail: mm.rekha@jainuniversity.ac.in Manish Srivastava ORCID ID: 0000-0001-6656-4376 E-mail: manish.srivastava1@nimsuniversity.org Reza Akhavan-Sigari ORCID ID: 0000-0001-6118-1704 E-mail: rasigari@yahoo.de References 1. Tungsubutra W, Tresukosol D, Krittayaphong R, et al. Acute coronary syndrome in 1366 patients at Siriraj Hospital: clinical characteristics, management and in- hospital outcomes. 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Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Submitted: 16 August 2024. Accepted: 24 September 2024. Early access: 28 November 2024. - 19 -