Interleukin-6 Inhibition for Patients with Acute Myocardial Infarction: A Systematic Review and Meta-Analysis

Summary

Objective:

To explore the outcomes associated with interleukin-6 (IL-6) pathway blockade, using tocilizumab, in patients with ST-elevation myocardial infarction (STEMI) and non (NSTEMI). Acute myocardial infarction (AMI) denotes myocardial necrosis due to ischemia and presents in distinct electrocardiographic phenotypes. Inflammation driven by IL-6 contributes to ischemia-reperfusion injury, with tocilizumab showing promise in reducing myocardial damage and improving outcomes.

Methods:

This work followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Framework and was registered in international prospective register of systematic reviews (PROSPERO). Relevant studies were identified through structured searches of PubMed, MEDLINE, the Cochrane Library, and Google Scholar up to June 2025, focusing on randomized and prospective investigations of IL-6 inhibition in AMI. Assessed outcomes included infarct size, inflammatory and cardiac biomarkers, major adverse cardiovascular events, and mortality.

Results:

Three randomized controlled trials including 344 patients were analyzed. All evaluated tocilizumab in STEMI or NSTEMI. Pooled data showed no significant difference between tocilizumab and placebo for recurrent myocardial infarction (relative risk [RR] = 0.47, 95% confidence limit [CI] = 0.07–3.05; I² = 44%; p = 0.43) or infection (RR = 0.85, 95% CI: 0.29–2.53; I² = 0%; p = 0.77). Mechanistic analysis demonstrated lower c-reactive protein (CRP) exposure, transient N-terminal pro-B-type natriuretic peptide (NT-proßNP) reductions, and attenuated troponin release in tocilizumab groups, indicating biological modulation of inflammatory and myocardial injury pathways during the acute phase. Benefits were greatest during hospitalization but diminished over time. Long-term outcomes, including ventricular remodeling, NT-proßNP at 6 months, and mortality, showed no significant group differences.

Conclusion:

The IL-6 inhibition with tocilizumab demonstrates early anti-inflammatory and cardioprotective effects in AMI, but consistent clinical benefits remain unproven, underscoring the need for larger, long-term trials to confirm efficacy and safety.

Introduction

Acute myocardial infarction (AMI) denotes myocardial necrosis resulting from ischemia. From a clinical perspective, patients are categorized into ST-segment elevation myocardial infarction (STEMI) and non ST-segment elevation myocardial infarction (NSTEMI) presentations according to findings on the electrocardiogram [1].

Inflammatory processes are central to the development of AMI, particularly during the ischemia reperfusion (I/R) phase. Reperfusion activates inflammatory pathways further aggravating myocardial damage. Current therapeutic techniques do not adequately target this acute inflammatory response, emphasizing the need for novel anti-inflammatory strategies [2].

Both atherosclerotic activity and myocardial damage are influenced by inflammatory pathways in which interleukin-6 (IL-6) is involved. Higher IL-6 concentrations have been linked to plaque vulnerability, vascular dysfunction, and worse clinical outcomes, and have been shown to independently predict cardiovascular mortality. The IL-6 receptor signaling can be blocked by tocilizumab, a monoclonal antibody designed to target this inflammatory pathway, thereby reducing systemic inflammation, suggesting a potential therapeutic role in limiting inflammation-driven cardiac damage [3,4].

This systematic review aims to explore the outcomes associated with IL-6 pathway blockade, using tocilizumab, in patients with STEMI and NSTEMI. Specifically, it will assess short-term outcomes (such as infarct size, myocardial salvage index, troponin release) and long-term outcomes (such as major adverse cardiovascular events, cardiac remodeling, mortality) to clarify the therapeutic potential of targeting IL-6 signaling in this high-risk population.

Methods

The conduct and reporting of this review were guided by the preferred reporting items for Systematic Reviews and Meta-Analysis (PRISMA) framework. Protocol details were recorded prospectively in the international prospective register of systematic reviews (PROSPERO) following finalization of eligibility criteria. This review seeks to determine the clinical and biological effects of IL-6 inhibition, including tocilizumab, in patients with AMI, focusing on short-term cardiac outcomes, long-term clinical endpoints, and mechanistic effects on inflammatory pathways, neutrophil function, and microvascular integrity.

The PICO framework

Population (P): Adults with AMI, encompassing STEMI and NSTEMI. Intervention (I): IL-6 inhibition, including tocilizumab. Comparison (C): Placebo or standard care. Outcomes (O): Short-term cardiac endpoints, including myocardial salvage index, infarct size, and troponin levels; major adverse cardiovascular events as measures of long-term clinical outcome, cardiac remodeling, and survival; and mechanistic outcomes related to inflammatory pathways, neutrophil activity, and microvascular function.

Eligibility was limited to studies with randomized or prospective cohort designs that enrolled adult patients with AMI who received IL-6 inhibitors (tocilizumab, sarilumab, or siltuximab). Both STEMI and NSTEMI populations were included, as the mechanism of IL-6 inhibition is expected to be similar across AMl Subtypes. Eligible studies reported outcomes related to cardiac function, inflammatory markers, or clinical endpoints including mortality, heart failure, or reinfarction. Only peer-reviewed studies involving human participants with full-text availability published since 2000 were considered. We excluded studies that did not evaluate IL-6 inhibitors as a therapeutic intervention or assessed IL-6 solely as a biomarker. Studies with case-control, cross-sectional, case-series, review, abstract, letter, or editorial designs were excluded as well as studies not conducted in the context of AMI, non-peer-reviewed publications, studies without full-text access, animal studies, and non-English publications.

A structured search strategy was used to locate studies assessing the effects of IL-6 pathway blockade in patients with AMI. The databases PubMed, MEDLINE (via Ovid), Google Scholar and the Cochrane Library were queried from the earliest indexed records to June 2025 using a combination of medical subject headings (MeSH) and free-text keywords: “Interleukin-6” or “IL-6” or “IL-6 inhibitor” or “tocilizumab” or “siltuximab” or “sarilumab” and “ST elevation myocardial infarction” or “STEMI” or “NSTEMI” or “Non-ST elevation myocardial infarction”.

Two independent reviewers conducted the initial screening of studies identified in Rayyan Al following application of predefined inclusion and exclusion criteria, study relevance was assessed through a staged screening process. Initial evaluation was performed at the title and abstract level, with potentially eligible studies subsequently undergoing full-text review. Disagreements arising during screening were resolved through consultation with a third reviewer. At each stage, eligibility criteria were applied consistently to ensure that only studies relevant to IL-6 inhibition in AMI were included.

Information was independently extracted using a standardized excel form, with data entries completed separately by 2 reviewers. Conflicts were settled by consensus or third reviewer input. Extracted variables included study descriptors such as author, year, country, and design, along with participant demographics, intervention characteristics including IL-6 inhibitor type, dose, route, timing, and duration, and comparator information involving placebo or standard care.

The outcomes collected were clinical endpoints (major adverse cardiovascular events, mortality, recurrent myocardial infarction (MI), heart failure), safety outcomes (adverse events, infections, hepatotoxicity), and biomarker or functional measures (IL-6, c-reactive protein (CRP), troponin, N-terminal pro-B-type natriuretic peptide (NT-proßNP), left ventricular ejection fraction, infarct size where available).

Assessment of methodological quality was conducted with the Cochrane collaboration risk of bias instrument (RoB-2) by 2 reviewers working independently. The evaluation encompassed domains related to the randomization process, adherence to intended interventions, completeness of outcome data, outcome measurement, and selective reporting. Each study was subsequently categorized as having low risk of bias, high risk of bias, or some concerns. Disagreements were addressed through consensus, with involvement of a third reviewer when necessary.

Summary tables were generated to present study characteristics and key outcomes. Data were synthesized descriptively to compare interventions, populations, and results, with patterns and differences across studies highlighted narratively. Findings from studies with comparable outcome measures were then pooled for quantitative synthesis. Meta-analysis were conducted using ReMan v5.4. Outcomes reported in ≥2 studies were pooled; dichotomous data were expressed as risk ratios (RRs) accompanied by 95% confidence limit (Cls). Statistical heterogeneity across studies was quantified with the I² statistic (low: 0–40%, moderate: 30-60%, substantial: 50–90%, considerable: 75–100%). Given the limited number of studies analyzed, heterogeneity was managed primarily through analytical restraint, with pooling limited to clinically comparable outcomes and all other variability addressed through narrative synthesis and conservative interpretation.

Results

The study selection process is illustrated in Fig. 1. A total of 346 records were identified through database searching. After removal of 99 duplicate records, 247 studies were screened based on title and abstract, of which 233 were excluded. 14 full-text articles were assessed for eligibility, and seven were excluded due to ineligible intervention focus or insufficient data. Ultimately, 7 studies were included in the systematic review and meta-analysis [5,6,7,8,9,10,11].

Fig. 1.

PRISMA diagram. PRISMA: preferred reporting items for systematic reviews and meta-analysis.

Three randomized controlled trials (RCTs) constituted the basis of this systematic review and meta-analysis; these were reported across 7 publications [5,6,7,8,9,10,11]. All studies evaluated IL-6 inhibition using tocilizumab in patients with STEMI or NSTEMI and were conducted in Norway and the United States of America (USA) between 2016 and 2024, with enrollment sizes spanning 28 to 199 participants.

The assessing the effect of anti-IL-6 (ASSAIL)-MI trial, reported in 4 publications, included 199 patients with STEMI, among enrolled participants, 101 received 280 mg of tocilizumab administered intravenously, while the remaining 98 were assigned to placebo [6,8,9,11]. The Kleveland trial, reported in 2 publications, enrolled 117 patients with NSTEMI who were randomized to intravenous tocilizumab or placebo [5,10]. The ST-segment analysis using wireless technology (STAT)-MI trial from the USA included 28 patients with STEMI or NSTEMI who received subcutaneous tocilizumab or placebo [7]. An overview of study characteristics and patient demographics is provided in Table 1.

Table 1.

Characteristics of the included studies?.

	Study Characteristics					Tocilizumab								Placebo
Trial	Author	Year	Design	Location	Sample size	Sample (IL-6 Group)	STEMI or NSTEMI	Gender		Mean Age	Mean BMI	Route	Dosage	Sample (Placebo Group)	Gender		Mean Age	Mean BMI
								Males	Females						Males	Females			Route	Dosage	Conclusion
ASSAIL-MI	Broch et al	2021	RCT	Norway	199	101	STEMI	80	21	62	27.1	IV	280 mg	98	87	11	60 ± 9	27.5 +-4.3	IV	100 ml NaCl 0.9%	Tocilizumab significantly increased Myocardial Salvage.
	Woxholt S et al	2023	RCT	Norway	199	101	STEMI	80	21	62	27.1	IV	28 mg	98	87	11	60 ± 9	27.5 ± 4.3	IV	100 ml NS	IL-6 & IL-8 were high in the Tocilizumab group but the inflammation was attenuated
	Kindberg et al	2024	RCT	Norway	199	101	STEMI	80	21	62	27.1	IV	280 mg	98	87	11	60 ± 9	27.5 ± 4.3	IV	100 ml NaCl 0.9%	Lower dsDNA and H3Cit by tocilizumab were associated with better MSI and smaller infarct size
	Huse et al	2022	RCT	Norway	199	101	STEMI	80	21	62	27.1	IV	280 mg	98	87	11	60 ± 9	27.5+-4.3	IV	100 ml NaCl 0.9%	Tocilizumab significantly reduced neutrophil counts, inflammation, and infarct size, resulting in improved myocardial salvage in STEMI patients. It was particularly effective in patients presenting >3 hours after symptom onset.
Klevel and	Kleveland et al	2016	RCT	Norway	117	58	NSTEMI	49	9	59.8	28.8	IV	280 mg	59	54	5	60.1	27.4	IV	100 ml NaCl 0.9%	Tocilizumab attenuated the inflammatory response and PCI related TnT release in NSTEMI
	Holte et al	2017	RCT	Norway	117	58	NSTEMI	55	3	57.8	28.8	IV	280 mg	59	59	0	59.3	27.1	IV	100 ml NaCl 0.9%	Tocilizumab did not affect CFR during hospitalisation or after 6 months. tocilizumab increased VcaM-1 levels during hospitalisation, but this was not associated with reduced CFR in these patients.
STAT-MI	Carroll et al	2017	RCT	United States	28	12	STEMI and NSTEMI	10	2	70.7	28.4	Subcut- aneous	162 mg	16	14	2	67.7	29.4	Subcut- aneous	NaCl 0.9%	No statistically significant differences in MACE were observed. CRP increased after administration of TCZ but this was not statistically significant.

AMI: acute myocardial infarction, ASSAIL-MI: assessing affect of il-6 in myocardial infarction, BMI: body mass index, CRP: C-reactive protein, dsDNA: double-stranded deoxyribonucleic acid, H3Cit: citrullinated histone H3, IL-6: interleukin-6, IL-8: interleukin-8, IV: intravenous, MACE: major adverse cardiovascular events, NaCl: sodium chloride, NSTEMI: non-ST-elevation myocardial infarction, PCI: percutaneous coronary intervention, RCT: randomized controlled trial, STAT-MI: short-term application of tocilizumab during myocardial infarction, STEMI: ST-elevation myocardial infarction, TCZ: tocilizumab, TnT: troponin T, VCAM-1: vascular cell adhesion molecule 1.

An evaluation of study quality was performed for each publication using the ROB-2 instrument. Overall quality assessment identified 6 publications as low bias risk, with a single publication classified as moderate quality due to some concerns on the selection of reported outcomes (Appendix 1). All 3 randomized clinical trials (RCTs) reported the outcome. When results were combined, outcomes with tocilizumab showed no measurable advantage over placebo based on the pooled (relative risk [RR] = 0.47, 95% CI = 0.07, 3.05, p = 0.43) with low heterogeneity (I² = 44%) (Fig. 2). All 3 RCTs reported the outcome. No statistically meaningful differences were observed between tocilizumab and placebo groups with pooled (RR = 0.85, 95% CI = 0.29, 2.53, p = 0.77) and 0 heterogeneity (I² = 0%) (Fig. 3). In the STAT-MI trial, Carroll et al. [7] observed a marked increase in CRP levels <24 hours post-treatment in the tocilizumab group followed by normalization by day 30. In the Kleveland study, Holte et al. [10] reported a correlation between high-sensitivity CRP (hsCRP) and troponin T (hsTnT) during hospitalization, which was not maintained at follow-up. In the ASSAIL-MI trial, Woxholt et al. [11] demonstrated stronger CRP-neutrophil associations in patients presenting after 3 hours. Additionally, Broch et al. [5] reported lower CRP area under the curve (AUC) during hospitalization in the tocilizumab group, although differences by baseline CRP levels were not significant (Table 2). Broch et al. [9] demonstrated in the ASSAIL-MI study that there was no separation in 6 month NT-proßNP levels across the tocilizumab and placebo groups (p = 0.25) suggesting no long-term effect on cardiac stress or ventricular remodeling. However, the Kleveland study reported by Kleveland et al. [5] demonstrated a significantly greater short-term reduction in NT-proßNP levels during hospitalization among patients receiving tocilizumab, relative to placebo (p < 0.001 versus p < 0.01) indicating a transient short-term biological effect on cardiac stress markers during hospitalization. (Table 3). In the STAT-MI trial, Carroll et al. [7] observed greater peak troponin I concentrations among patients treated with tocilizumab than among those receiving placebo, although variability and infarct heterogeneity may limit interpretation. Conversely, Kleveland et al. [5] showed significantly lower hsTnT AUC in the tocilizumab group with normalization by 3 to 6 months. Holte et al. [10] identified an association linking hsTnT levels with systemic inflammatory markers. In the ASSAIL-MI trial, Woxholt et al. [11] found that troponin T levels correlated with IL-6 and IL-8 especially in early presenters (<3 hours). Finally, Broch et al. [9] reported a lower troponin T AUC with tocilizumab treatment, although statistical significance was not achieved (p = 0.13) (Appendix 2).

Appendix 1.

Risk of bias assessment of included studies. Risk of bias evaluation of the included randomized controlled trials using the Cochrane Risk of Bias 2 (RoB-2) tool across 5 domains (D1–D5), with overall judgment shown for each study. Green indicates low risk of bias, and yellow indicates some concerns.

Fig. 2.

Meta-analysis of the risk of myocardial infarction. Forest plot showing the pooled risk ratio (95% confidence interval) for recurrent myocardial infarction comparing tocilizumab with placebo. The diamond represents the pooled effect estimate, and heterogeneity statistics are reported.

Fig. 3.

Meta-analysis of the risk of infection. Forest plot showing the pooled risk ratio (95% confidence interval) for infection comparing tocilizumab with placebo. The diamond represents the pooled effect estimate, and heterogeneity statistics are reported.

Table 2.

Min findings of CRP levels assessment.

Trial	Study	Outcome	Main findings
STAT-MI	Carroll et al	CRP levels	CRP levels increased markedly within 24 hours after treatment in the tocilizumab group (57.3 ± 89.6 mg/L) compared to the placebo group (14.4 ± 30.2 mg/L) despite similar baseline values. By day 30, CRP levels in the tocilizumab group returned closer to baseline (20.6 ± 47.6 mg/L), while the placebo group maintained lower CRP levels (3.1 ± 2.9 mg/L). These findings suggest a transient post-treatment inflammatory response in the tocilizumab group.
Kleveland	Holte et al	Correlation between hsCRP and hsTnT	During hospitalization, there was a positive correlation between hsCRP and hsTnT in both treatment groups indicating a link between systemic inflammation and myocardial injury. However, these correlations were not observed at follow-up. Additionally, no significant correlations were found between hsCRP or hsTnT and CFR or endothelial activation markers at any time point except for a positive correlation between hsTnT and vWF in the tocilizumab group during hospitalization.
ASSAIL-MI	Woxholt et al	CRP levels	The CRP was more strongly associated with neutrophils in patients presenting after three hours indicating a delayed systemic inflammation.
	Broch et al	CRP levels	The AUC of CRP during hospitalization was substantially lower in the tocilizumab group compared to the placebo group suggesting a strong anti-inflammatory effect. When stratified by baseline CRP levels, patients with CRP ≤ 4.9 mg/L showed a greater reduction (mean difference = –9.3; 95% CI: –19.3 to 3.3), while those with CRP > 4.9 mg/L had a smaller reduction (mean difference = 2.6; 95% CI: –7.3 to 12.5). However, these differences did not reach statistical significance (p = 0.09)

HsCRP: high-sensitivity C-reactive protein, hsTnT: high-sensitivity troponin T, vWF: von Willebrand factor, CRP: C-reactive protein, AUC: area under the curve, CI: confidence interval, CFR: coronary flow reserve, ASSAIL-MI: assessing the effect of anti-il-6 treatment in myocardial infarction.

Table 3.

Main findings of NT-proβNP assessment.

Trial	Study	Outcome	Main findings
ASSAIL-MI	Broch et al	NT-proβ NP	There were no significant differences between the tocilizumab and placebo groups in baseline-adjusted LVEDV (p = 0.54) or NT-proβNP levels (p = 0.25) at 6 months indicating that tocilizumab did not have a measurable long-term impact on left ventricular remodeling or cardiac stress as reflected by NT-proβNP concentrations.
Kleveland	Kleveland et al	NT-proβNP	During hospitalization, NT-proβNP levels decreased from baseline to day 3 in both groups with a more pronounced reduction observed in the tocilizumab group. Specifically, NT-proβNP dropped from 259 (180–372) ng/L at baseline to 126 (86–185) ng/L on day 3 in the tocilizumab group (p < 0.001) compared to a decrease from 283 (202–395) ng/L to 204 (144–291) ng/L in the placebo group (p < 0.01).

NT-proβNP: N-terminal pro-β-type natriuretic peptide, LVEDV: left ventricular end-diastolic volume.

Appendix 2.

Main findings of troponin assessment. AMI: acute myocardial infarction, ASSAIL-MI: assessing affect of Il-6 in myocardial infarction, AUC: area under the curve; bsCRP: baseline C-reactive protein; CFR: coronary flow reserve; IL-6: interleukin-6, IL-8: interleukin-8, STAT-MI: short-term application of tocilizumab during myocardial infarction, STEMI: ST-elevation myocardial infarction, HsCRP: high-sensitivity C-reactive protein, hsTnT: high-sensitivity troponin T.

Trial	Study	Outcome	Main findings
STAT-MI	Carroll et al.	Troponin	Peak troponin I levels were higher in the tocilizumab group (23.82 ± 56.22 ng/mL) compared to the placebo group (6.97 ± 9.64 ng/mL) though the large standard deviation in the tocilizumab group suggests substantial variability. While more patients in the placebo group had STEMI, the higher troponin levels in the tocilizumab group may reflect differences in infarct characteristics or timing rather than a direct effect of the treatment.
Kleveland	Kleveland et al.	Troponin	The hsTnT levels during hospitalization were significantly lower in the tocilizumab group compared to placebo with a 1.5-fold higher median AUC observed in the placebo arm (234 vs. 159 ng/L/h; p= 0.007). Notably, hsTnT increased significantly within the first 24 hours in the placebo group but remained stable in the tocilizumab group suggesting a potential cardioprotective effect. The hsTnT levels had normalized in both groups by three and six months with no significant differences—this indicates that the effect was limited to the acute phase.
	Holte et al.	Troponin	HsTnT showed a positive correlation during hospitalization in both treatment groups indicating a link between systemic inflammation and myocardial injury in the acute phase. Additionally, apart from a positive correlation between hsTnT and vWF in the tocilizumab group during hospitalization, there were no significant correlations between hsCRP or hsTnT and CFR or other markers of endothelial activation at any time point
ASSAIL-MI	Woxholt et al.	Troponin	Troponin T levels showed weak to moderate positive correlations with inflammatory markers particularly IL-6 and IL-8 during hospitalization. These associations were stronger in patients who presented within three hours of symptom onset.
	Broch et al.	Troponin	Troponin T AUC was lower with tocilizumab (1,614 versus 2,357 ng/L/h) reflecting reduced myocardial injury, but the difference was not statistically significant (p = 0.13).

Discussion

This systematic review and meta-analysis assessed tocilizumab-mediated IL-6 pathway modulation in patients with AMI, incorporating data from three randomized controlled trials involving both STEMI and NSTEMI populations. While pooled analyses did not demonstrate a measurable reduction in recurrent myocardial infarction or infection with tocilizumab relative to placebo, the systematic review identified consistent biological effects on inflammatory activity. Tocilizumab was associated with reductions in inflammatory biomarkers, particularly CRP, and transient changes in cardiac injury markers such as troponin and NT-proßNP in some settings.

However, these effects were not accompanied by clear clinical improvement over time. Inflammatory processes observed in AMI are partly driven by IL-6 signaling, contributing to both tissue damage and systemic immune activation [12]. Suppression of CRP exposure during hospitalization, as observed in the ASSAIL-MI trial, and short term decline in NT-proßNP in the Kleveland study are consistent with effective attenuation of inflammatory signaling. Variation in inflammatory patterns according to time of presentation, as reported by Woxholt et al. suggests that timing of IL-6 inhibition may influence biological response, although this hypothesis requires confirmation in larger studies.

The effects on cardiac injury markers were heterogeneous across trials. In the Kleveland and ASSAIL-MI studies, tocilizumab was associated with reduced troponin burden during hospitalization, whereas the STAT-MI trial reported higher peak troponin levels, likely reflecting small sample size and mixed infarct subtypes. Short term NT-proßNP reductions were observed in Kleveland but were not sustained at 6 month follow up in ASSAIL-MI, indicating limited impact on ventricular remodeling or long-term clinical benefit.

Clinically, these findings highlight the difficulty of converting anti-inflammatory strategies into meaningful outcome improvement in AMI. Although IL-6 blockade is more targeted than broader anti-inflammatory therapies, clinical event reduction has not yet been demonstrated. A randomized clinical trial evaluating IL-1 inhibition in STEMI similarly showed reductions in CRP without significant effects on infarct size or remodeling [13].

Our analysis showed that IL-6 inhibition with tocilizumab did not significantly reduce recurrent myocardial infarction or infection, despite consistent biological effects. In contrast, IL-6 receptor antagonists have demonstrated survival benefit in systemic inflammatory conditions such as severe coronavirus disease (COVID)-19 and have proven efficacy in chronic inflammatory diseases such as rheumatoid arthritis [14,15]. This contrast suggests that IL-6 targeted therapy in AMI may be constrained by the localized nature and narrow therapeutic window of myocardial injury.

Several aspects strengthen this work, including its status as the first synthesis combining systematic review and meta-analytic methods focused specifically on IL-6 inhibition in the acute setting of MI. It includes data from multiple RCTs with differing AMI subtypes, administration routes, and biomarker profiles, allowing integration of the available evidence. Study quality was generally high, supported by a rigorous assessment of bias performed with the ROB-2 instrument.

Importantly, although IL-6 inhibition demonstrated consistent biological effects on inflammatory and cardiac biomarkers, these mechanistic findings did not translate into clear improvements in clinically meaningful outcomes in the currently available trials and should therefore be interpreted as evidence of target engagement rather than clinical benefit.

Although individual trials such as ASSAIL-MI have previously described IL-6 therapy within specific AMI populations, the present analysis provides the first integrated synthesis of both STEMI and NSTEMI cohorts, identifying timing of therapy and infarct phenotype as potential modifiers that may inform the design of future adequately powered trials.

Further investigation of IL-6 inhibition in AMI is warranted. Future studies should be larger, multicenter, and powered for clinical endpoints such as major adverse cardiovascular events, heart failure, and mortality. Stratification by timing of presentation, infarct type, and baseline inflammatory status may clarify which patient population derive the greatest benefit. Long term safety assessment remains essential, particularly with respect to infection risk.

This review draws on evidence from 3 randomized controlled trials with a combined total of 344 participants. As a result, the conclusions are constrained in terms of robustness, precision, and applicability to broader populations. The limited number of available trials, together with their relatively small sample sizes, increases susceptibility to random variation and limits the ability to reliably detect treatment effects across outcomes such as infarct size, myocardial injury, inflammatory markers, mechanistic endpoints, and longer term clinical events. Consequently, the findings are best interpreted as exploratory in nature rather than conclusive.

In conclusion, IL-6 inhibition with tocilizumab in the acute phase of myocardial infarction demonstrates consistent biological effects on inflammatory and myocardial injury related markers during the acute phase of AMI, as reflected by changes in CRP, troponin, and NT-proßNP. However, these biochemical effects have not translated into consistent reductions in clinical events. While the therapeutic potential of IL-6 blockade remains of interest, large scale trials are required before its integration into standard AMI care.

Disclosure

AI tools have been used only in the phrasing and paraphrasing of the manuscript content it was never used in generating knowledge, we thoroughly reviewed the rephrased content that was generated by AI and double-checked its accuracy. The rephrased sections include the abstract, introduction, methods, results, and conclusion, merely for enhancing coherence. The manuscript or its contents have never been published anywhere else in English or any other language. The PROSPERO protocol is registered in here (https://www.crd.york.ac.uk/PROSPERO/view/CRD420251109443.). The article wasn't presented in any conference before. Authors have no conflict of interest and the work was not supported or funded by any drug company or other institutions.

Acknowledgment

We would like to thank the American Manuscript Editors (www.americanmanuscripteditors.com) for editorial assistance with the English language.