Tocilizumab in Acute Coronary Syndromes: A Systematic Review of Randomized Controlled Trials

This systematic review synthesizes the randomized controlled trial (RCT) evidence for tocilizumab, an interleukin-6 (IL-6) receptor antagonist, as an adjunctive therapy in acute coronary syndrome (ACS). IL-6 is a central mediator of the inflammatory response that follows myocardial infarction and contributes to ischemia-reperfusion injury, positioning its blockade as a plausible cardioprotective strategy. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidance, we searched PubMed/MEDLINE, Embase, Cochrane Library, and Scopus for RCTs of tocilizumab administered during the acute phase of ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) versus placebo or standard of care; risk of bias was assessed using the Cochrane RoB 2.0 tool. Given the substantial heterogeneity in population, dosing, and primary endpoints, findings were synthesized narratively rather than pooled. Four trials comprising 439 analyzed patients met the eligibility criteria, spanning NSTEMI and STEMI populations and both intravenous and subcutaneous dosing regimens, one of which was stopped early for futility. In the three intravenously dosed trials, tocilizumab more than halved the C-reactive protein area under the curve relative to placebo (all p < 0.001), with two trials also showing lower troponin release. One trial additionally demonstrated a significant improvement in myocardial salvage index and reduced microvascular obstruction on cardiac magnetic resonance imaging (CMRI), without significant benefit on the final infarct size or six-month clinical outcomes; a separate, higher-risk trial found no significant benefit on infarct size, troponin, or neurohormonal activation despite comparable suppression of inflammation. Major adverse cardiac events did not differ significantly between arms in either trial assessing this endpoint, and the smallest, subcutaneously dosed trial raised an unreplicated cardiac tamponade signal. Two of the four trials were judged overall low risk of bias. Tocilizumab consistently attenuates the acute inflammatory response and, in one trial, improves imaging surrogates of myocardial salvage, but evidence for clinical benefit is absent, and the trial base remains too small and heterogeneous to support meta-analytic pooling or practice change. Larger, adequately powered trials with harmonized endpoints and blinded safety adjudication are needed.