Timing of invasive strategy in NSTE-ACS patients and effect on clinical outcomes: A systematic review and meta-analysis of randomized controlled trials


      • RCTs produced conflicting results on effects of early invasive strategy in NSTE-ACS.
      • Pooled data analysis showed reduction in recurrent ischemia and no mortality benefit.
      • There is high between-study heterogeneity in the reported rates of new MI.
      • Heterogeneity stems from ambiguous new MI definition and early intervention timing.
      • Impact of timing on new MI rates is stronger in studies with higher PCI rates.



      Previous randomized controlled trials (RCTs) have produced conflicting results on the effects of early versus delayed invasive strategy in NSTE-ACS patients.


      To perform up to date meta-analysis on the pooled data sample comparing early versus delayed invasive strategy, and to explore potential causes for the observed high statistical heterogeneity.


      MEDLINE via Pubmed, Central, Google Scholar, Clinical Trials Registry, Current controlled study and registry and relevant conference proceedings were searched. RCTs were included that directly compared early versus delayed invasive strategy and reported rates of death, new myocardial infarction (MI) and/or recurrent ischemia.


      10 RCTs with 6089 patients were included. Time to coronary angiography varied from 0.5 to 24 h in the early and from 20.5 to 86 h in the delayed group. Meta-analysis showed no significant difference in mortality (OR = 0.83, 95%CI 0.64–1.08, P = 0.16), and similar new MI rates (OR = 1.02, 95%CI 0.63–1.64, P = 0.94). The rate of recurrent ischemia was reduced in patients undergoing early coronary angiography (OR = 0.56, 95%CI 0.40–0.79, P = 0.001). Subgroup analysis indicated that the rate of new MI tended to depend on the study-specific endpoint definition (p for difference between subgroups 0.11), while a meta-regression revealed association of new MI rates with the within-study delay to coronary angiography (p = 0.05).


      Early invasive strategy appears to reduce the occurrence of recurrent ischemia, but confers no mortality benefit. The true effect on the occurrence of new MI is obscured by the high between-study heterogeneity that stems mainly from non-uniform timing of early intervention and new MI definitions across the trials.


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