Key result
Intracoronary thrombolysis during primary PCI cuts MACE ~26%, driven by non- and moderately specific agents.
Why the study?
Clinical trials of adjunctive intracoronary thrombolysis during primary PCI for STEMI have yielded deeply polarized results and fragmented guidelines, possibly driven by differences in the fibrin specificity of the agents used.
Does adjunctive intracoronary thrombolysis during primary PCI reduce major adverse cardiac events in patients with STEMI, and does efficacy depend on the fibrin specificity of the thrombolytic agent?
Meta-Analysis (n=2,122)
Does adjunctive intracoronary thrombolysis during primary PCI reduce major adverse cardiac events in patients with STEMI, and does efficacy depend on the fibrin specificity of the thrombolytic agent?
The clinical efficacy of adjunctive intracoronary thrombolysis during primary PCI for STEMI is driven by a pharmacological class effect, with non-fibrin and moderately fibrin-specific agents significantly reducing MACE while highly fibrin-specific agents like alteplase provide no benefit.
Supports adjunctive non- or moderately fibrin-specific thrombolysis in STEMI PCI; extends prior trials by resolving heterogeneity via drug-class stratification.
Background Despite successful epicardial restoration via primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), microvascular obstruction (MVO) occurs in up to 40% of patients. While adjunctive intracoronary (IC) thrombolysis aims to dissolve distal micro-thrombi, clinical trials have yielded deeply polarized results, leading to fragmented guidelines. We hypothesized that this discrepancy is not a failure of the strategy, but a "specificity paradox" driven by the pharmacological properties of the agents used. Methods and results We systematically searched PubMed, Embase, and Cochrane CENTRAL for randomized controlled trials (RCTs) evaluating IC thrombolysis during primary PCI. To address the primary hypothesis, trials were stratified into non-fibrin specific, moderately fibrin-specific, and highly fibrin-specific agents. The primary endpoint was major adverse cardiac events (MACE). Thirteen RCTs comprising 2,122 patients (including the recent STRIVE 2025 trial) were included. Overall, IC thrombolysis significantly reduced MACE (Risk Ratio [RR] 0.74; 95% CI 0.62–0.90; p=0.002). However, subgroup stratification revealed a highly significant interaction by drug class (p=0.003, I2=82.6%). Non-fibrin specific agents (RR 0.38; 95% CI 0.19–0.75) and moderately specific agents (RR 0.62; 95% CI 0.47–0.84) yielded robust clinical benefits. Conversely, highly fibrin-specific agents (e.g., alteplase) demonstrated no clinical benefit (RR 1.04; 95% CI 0.81–1.35). Statistical heterogeneity was entirely eliminated within all three defined subgroups (I2=0%). Conclusion The efficacy of adjunctive IC thrombolysis in STEMI is strictly dictated by a pharmacological class effect. While contemporary highly fibrin-specific agents demonstrate no clinical benefit, non-fibrin and moderately specific agents significantly improve outcomes. Future trials must prioritize the evaluation of non-fibrin restricted agents to address microvascular obstructionMace Intracoronary Thrombolysis
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Azuelo et al. (2026) conducted a meta-analysis in ST-segment elevation myocardial infarction (STEMI) (n=2,122). Adjunctive intracoronary thrombolysis (non-fibrin, moderately fibrin-, and highly fibrin-specific agents) vs. Primary PCI without intracoronary thrombolysis / control was evaluated on Major adverse cardiac events (MACE) (RR 0.74, 95% CI 0.62-0.90, p=0.002). Adjunctive intracoronary thrombolysis during primary PCI for STEMI reduced MACE overall (RR 0.74; 95% CI 0.62-0.90; p=0.002), driven by non-fibrin and moderately specific agents.
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