Timing of Invasive Strategy in NSTE-ACS and Outcomes

Study Questions:

What is the optimal timing of the invasive strategy in non–ST-segment elevation acute coronary syndromes (NSTE-ACS)?


A previous meta-analysis of seven randomized clinical trials comparing early and delayed invasive strategies in NSTE-ACS with three new randomized clinical trials identified in a search of the published research (n = 10 trials, n = 6,397 patients) was updated. The primary endpoint of the meta-analysis was the rate of death. Secondary endpoints included myocardial infarction (MI), major bleeding, recurrent angina or refractory angina, and in-hospital length of stay.


The median time between randomization and angiography ranged from 0.5 to 14 hours in the early group and from 20.5 to 86 hours in the delayed group. There was no difference in the primary endpoint of mortality (4% vs. 4.7%; random-effects odds ratio [OR], 0.85; 95% confidence interval [CI], 0.67-1.09; p = 0.20; I2 = 0%). The rate of MI was also similar (6.7% vs. 7.7%; random-effects OR, 0.88; 95% CI, 0.53-1.45; p = 0.60; I2 = 77.5%). An early strategy was associated with a reduction in recurrent ischemia or refractory angina (3.8% vs. 5.8%; random-effects OR, 0.55; 95% CI, 0.40-0.74; p = 0.01; I2 = 28%) and a shorter in-hospital stay (median 112 hours [interquartile range, 61-158 hours] vs. 168 hours [interquartile range, 90.3-192 hours]; random-effects standardized mean difference, -0.40; 95% CI, -0.59 to -0.21; p < 0.01; I2 = 79%). Major bleeding was similar in the two groups (3.9% vs. 4.2%; random-effects OR, 0.94; 95% CI, 0.73-1.22; p = 0.64; I2 = 0%).


The authors concluded that an early invasive strategy does not reduce the risk for death or MI compared with a delayed strategy.


This updated meta-analysis suggests that an early invasive strategy does not translate into any mortality benefit compared with a delayed invasive strategy. The only significant clinical difference observed in the present meta-analysis was reductions in refractory angina and refractory angina with an early invasive strategy. However, it is important to note that both early and delayed strategies were associated with similar rates of major bleeding, confirming that an early intervention in this clinical setting is safe. Future trials need to assess whether the results are different depending on subgroups of patients on the basis of their risk profiles, and whether these results are valid for patients without pretreatment with P2Y12 antagonists.

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