{
  "abstract": "Background Guidelines strongly recommend reperfusion therapy, including thrombolysis and percutaneous coronary intervention, for ST-elevation myocardial infarction but contraindicate its use in most non-ST-elevation acute coronary syndromes (ACS). This practice largely stems from the landmark fibrinolytic therapy trialists (FTT) meta-analysis, which reported no benefit in patients without ST elevation (STE). However, the FTT included a subgroup from the ISIS-3 trial with substantial methodological issues, potentially obscuring a genuine treatment effect.Methods We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing thrombolysis vs placebo or no thrombolysis in ACS. Patients were grouped by ECG findings: STE, ST depression (STD) or absence of STE. All-cause mortality was extracted from each trial’s short-term follow-up (typically 21–35 days). We reassessed outcomes with and without inclusion of the ISIS-3 ‘uncertain diagnosis’ subgroup.Results Nine RCTs (40 226 patients) were analysed. Thrombolysis significantly reduced mortality in patients without STE (excluding isolated STD) (risk ratio (RR): 0.799; 95% CI 0.668 to 0.956; I²=0%). Including the ISIS-3 ‘uncertain diagnosis’ subgroup (representing 42% of the non-STE population) would have eliminated the statistical significance in non-STE patients (RR: 0.928; 95% CI 0.694 to 1.242) and markedly increased heterogeneity (I²=71%).Conclusion In historical RCTs, thrombolysis was associated with lower short-term mortality in non-STE presentations excluding isolated ST-segment depression, while isolated STD showed no benefit. Legacy conclusions hinge on outdated methods, delayed treatment and heterogeneous ECG definitions (and are sensitive to ISIS-3). This study exposes a material evidence gap in the foundation of current guidelines. Contemporary randomised trials with prespecified ECG criteria, rapid treatment windows and rigorous safety adjudication are needed.PROSPERO registration number CRD42024573681.",
  "authors": [
    {
      "affiliations": [
        "Cardiology, Instituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil"
      ],
      "name": "José Nunes de Alencar"
    },
    {
      "affiliations": [
        "Federal University of Uberlandia, Uberlandia, Brazil"
      ],
      "name": "Márcio Henrique de Jesus Oliveira"
    },
    {
      "affiliations": [
        "College of Higher Education of the United Amazon, Belém, Brazil"
      ],
      "name": "Elisio Bulhoes"
    },
    {
      "affiliations": [
        "Departament of Medicine University Ninth of July, São Paulo, Brazil"
      ],
      "name": "Carlos Alexandre Farias"
    },
    {
      "affiliations": [
        "Federal University of the Minas Triangle, Uberaba, Brazil"
      ],
      "name": "Julia Camargo Kabariti"
    },
    {
      "affiliations": [
        "Federal University of the Minas Triangle, Uberaba, Brazil"
      ],
      "name": "Henrique Champs Carvalho"
    },
    {
      "affiliations": [
        "Carolinas Medical Center, Charlotte, North Carolina, USA"
      ],
      "name": "Harvey Pendell Meyers"
    },
    {
      "affiliations": [
        "Emergency Department, Hennepin County Medical Center, Minneapolis, Minnesota, USA",
        "Emergency Medicine, University of Minnesota System, Minneapolis, Minnesota, USA"
      ],
      "name": "Stephen W Smith"
    }
  ],
  "title": "Thrombolysis in non-ST-elevation myocardial infarction: systematic review and meta-analysis of randomised controlled trials",
  "uid": "6c52e51c-b33d-5e60-84ac-17d3b7b02ade"
}