Importance of Risk Assessment in Timing of Invasive Coronary Evaluation and Treatment of Patients With Non-ST-Segment-Elevation Acute Coronary Syndrome: Insights From the VERDICT Trial

Abstract

Background The optimal timing of invasive examination and treatment of high-risk patients with non-ST-segment-elevation acute coronary syndrome has not been established. We investigated the efficacy of early invasive coronary angiography compared with standard-care invasive coronary angiography on the risk of all-cause mortality according to the GRACE (Global Registry of Acute Coronary Events) risk score in a predefined subgroup analysis of the VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) trial. Methods and Results Patients with clinical suspicion of non-ST-segment-elevation acute coronary syndrome with ECG changes indicating new ischemia and/or elevated troponin, in whom invasive coronary angiography was clinically indicated and deemed logistically feasible within 12 hours, were eligible for inclusion. Patients were randomized 1:1 to an early (≤12 hours) or standard (48-72 hours) invasive strategy. The primary outcome of the present study was all-cause mortality. Of 2147 patients randomized in the VERDICT trial, 2092 patients had an available GRACE risk score. Of these, 1021 (48.8%) patients had a GRACE score >140. During a median follow-up of 4.1 years, 192 (18.8%) and 54 (5.0%) patients died in the high and low GRACE score groups, respectively. The risk of death with the early invasive strategy was increased in patients with a GRACE score ≤140 (hazard ratio [HR], 2.04 [95% CI, 1.16-3.59]), whereas there was a trend toward a decreased risk of death with the early invasive strategy in patients with a GRACE score >140 (HR, 0.83 [95% CI, 0.63-1.10]) (Pinteraction=0.006). Conclusions In patients with non-ST-segment-elevation acute coronary syndrome, we found a significant interaction between timing of invasive coronary angiography and GRACE score on the risk of death. Randomized clinical trials are warranted to establish the efficacy and safety among high-risk and low-risk patients with non-ST-segment-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02061891.

Keywords: GRACE score; acute coronary syndrome; heart failure; invasive coronary angiography; mortality.

Conflict of interest statement

Dr Kofoed reports research grants from AP Møller og hustru Chastine McKinney Møllers Fond, The John and Birthe Meyer Foundation, Research Council of Rigshopitalet, the University of Copenhagen, the Danish Heart Foundation, the Lundbeck Foundation, the Danish Agency for Science, Technology and Innovation by the Danish Council for Strategic Research, and Novo Nordisk Foundation; and unrestricted research grants from Canon Medical Systems. Dr Torp‐Pedersen reports grants from Bayer and grants from Novo Nordisk outside the submitted work. Dr Clemmensen reports personal fees from Boehringer Ingelheim, ACI Clinical, and Bayer outside the submitted work. Dr Engstrøm reports personal fees from Abbott outside the submitted work. Dr Køber reports personal fees from speakers honoraria from Novo Nordisk, Novartis, AstraZeneca and Boehringer outside the submitted work. The remaining authors have no disclosures to report.

Figures

Figure 1. Absolute risk of death according to GRACE score (above/below median).

A, GRACE score <140. B, GRACE score >140. GRACE indicates Global Registry of Acute Coronary Events.

Figure 2. Absolute risk of secondary outcomes according to GRACE score (above/below median).

A, Heart failure hospitalization: GRACE score <140. B, Heart failure hospitalization: GRACE score >140. C, Nonfatal acute myocardial infarction: GRACE score <140. D, Nonfatal acute myocardial infarction: GRACE score >140. E, Refractory myocardial ischemia: GRACE score <140. F, Refractory myocardial ischemia: GRACE score >140. G, Repeat coronary revascularization: GRACE score <140. H, Repeat coronary revascularization: GRACE score >140. GRACE indicates Global Registry of Acute Coronary Events.

Figure 3. Treatment effect on outcomes according to GRACE score (above/below median).

AMI indicates acute myocardial infarction; GRACE, Global Registry of Acute Coronary Events; and ICA, invasive coronary angiography.

Figure 4. Treatment effect on the primary outcome of death according to the components of the GRACE score.

Units for creatinine are milligrams per deciliter. Units for systolic blood pressure are millimeters of mercury. GRACE indicates Global Registry of Acute Coronary Events; and ICA, invasive coronary angiography.