Optimal Timing of an Invasive Strategy in NSTE-ACS Patients

Study Questions:

What is the optimal timing of coronary angiography in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS)?


The investigators identified randomized controlled trials comparing an early versus a delayed invasive strategy in patients presenting with NSTE-ACS by searching MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. They included trials that reported all-cause mortality at least 30 days after in-hospital randomization and for which the trial investigators agreed to collaborate (i.e., providing individual patient data or standardized tabulated data). The authors pooled hazard ratios (HRs) using random-effects models. This meta-analysis is registered at PROSPERO (CRD42015018988).


Eight trials (n = 5,324 patients) with a median follow-up of 180 days (interquartile range [IQR], 180–360) were included. Overall, there was no significant mortality reduction in the early invasive group compared with the delayed invasive group (HR, 0.81; 95% CI, 0.64–1.03; p = 0.0879). In prespecified analyses of high-risk patients, we found lower mortality with an early invasive strategy in patients with elevated cardiac biomarkers at baseline (HR, 0.761; 95% CI, 0.581–0.996), diabetes (0.67, 0.45–0.99), a GRACE risk score >140 (0.70, 0.52–0·.5), and aged ≥75 years (0.65, 0.46–0.93), although tests for interaction were inconclusive.


The authors concluded that an early invasive strategy does not reduce mortality compared with a delayed invasive strategy in all patients with NSTE-ACS.


This collaborative meta-analysis reports that in NSTE-ACS patients, there was no significant mortality benefit with an early invasive strategy compared with a delayed invasive strategy. However, pre-defined subgroup analyses suggested lower mortality in four high-risk subgroups: those with elevated cardiac biomarkers at baseline, diabetes, GRACE risk score >140 points, and aged ≥75 years, although tests for risk–treatment interactions were not statistically significant. A large, prospective confirmatory trial would be needed to obtain definitive evidence of whether an early invasive strategy is beneficial compared with a delayed invasive strategy in these high-risk subgroups, as the current study findings should be considered hypothesis generating. For now, it would be prudent to follow the current guidelines on management of NSTE-ACS regarding risk-based timing of coronary angiography.

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