What guides the timing of angiogram and angioplasty in patients with acute coronary syndrome, particularly in relation to the Grace risk score?

GRACE Risk Score and Timing of Angiography in Acute Coronary Syndrome

Direct Recommendation

For patients with NSTE-ACS and a GRACE score >140, perform coronary angiography within 24 hours of hospital admission; for patients with GRACE score ≤140, angiography can be safely delayed beyond 24 hours or managed with a selective invasive approach. 1

Risk Stratification Framework

Very High-Risk Criteria (Immediate Angiography <2 Hours)

Proceed immediately to the catheterization laboratory regardless of GRACE score if any of the following are present: 1, 2

• Hemodynamic instability or cardiogenic shock
• Recurrent or ongoing chest pain refractory to medical treatment
• Life-threatening arrhythmias or cardiac arrest
• Mechanical complications of MI (papillary muscle rupture, ventricular septal defect, free wall rupture)
• Acute heart failure with refractory angina or ST-segment deviation
• Recurrent dynamic ST- or T-wave changes, particularly with intermittent ST-elevation

High-Risk Criteria (Early Angiography <24 Hours)

The GRACE score >140 is the primary determinant for early invasive strategy timing in stabilized patients. 1 Other high-risk features warranting early angiography include: 1

• Rise or fall in cardiac troponin compatible with MI
• Dynamic ST- or T-wave changes (symptomatic or silent)

Evidence Supporting GRACE Score Threshold of 140

The TIMACS trial demonstrated significant heterogeneity in outcomes based on GRACE risk stratification: 1

• Patients with GRACE >140: Early intervention (median 14 hours) reduced the primary ischemic endpoint from 21.0% to 13.9% (HR 0.65,95% CI 0.48-0.89, P=0.006)
• Patients with GRACE ≤140: No benefit from early intervention—outcomes were 6.7% vs 7.6% in delayed vs early groups (HR 1.12,95% CI 0.81-1.56, P=0.48)

The VERDICT trial confirmed this interaction, showing benefit with early invasive strategy only in patients with GRACE >140 (HR 0.81,95% CI 0.67-1.00 vs HR 1.21,95% CI 0.92-1.60 for GRACE ≤140; P for interaction=0.02). 1

Critical Caveats About GRACE Score Calculation

Use the GRACE risk score for in-hospital death when applying the >140 threshold, as this is what the TIMACS and VERDICT trials validated. 1 Different GRACE score versions (6-month, 1-year, 3-year mortality) use different variable weighting and can produce substantially different scores for the same patient, potentially leading to incorrect treatment decisions. 1

The GRACE >140 threshold was validated using conventional troponin or CK-MB, not high-sensitivity troponin. 1 The applicability of this threshold in the high-sensitivity troponin era has not been formally validated, though the score remains accurate for risk stratification. 3

Timing Definitions and Practical Implementation

• Immediate: <2 hours from hospital admission 1
• Early: <24 hours from hospital admission 1
• Delayed: >24 hours from hospital admission 1

There is no evidence that angiography within the first few hours provides incremental benefit over angiography at 12-24 hours in stabilized high-risk patients. 1 The ABOARD trial demonstrated that immediate intervention (median 70 minutes) provided no advantage over delayed intervention (median 21 hours) in unselected NSTE-ACS patients. 1

Low-to-Intermediate Risk Patients (GRACE ≤140)

A selective invasive strategy is appropriate for patients with GRACE ≤140, where angiography is performed only if: 1

• Medical therapy fails to control symptoms
• Objective evidence of ischemia develops on stress testing
• Clinical deterioration occurs during observation

This approach is supported by the lack of benefit from routine early intervention in this population across multiple trials. 1

Additional Benefits of Early Strategy in High-Risk Patients

Beyond mortality reduction, early invasive strategy in GRACE >140 patients significantly reduces: 1

• Refractory ischemia (3.3% vs 1.0%, P<0.001)
• Recurrent MI
• Length of hospital stay

The occurrence of refractory ischemia is associated with a more than 4-fold increase in risk of subsequent MI, making its prevention clinically meaningful. 1

Contemporary Risk Assessment

The GRACE score remains accurate for risk stratification despite improvements in contemporary ACS treatment. 3 Validation studies from 2000-2016 showed consistent discrimination for mortality prediction (AUC 0.75-0.87 for 7-day mortality, 0.79-0.84 for 1-year mortality) across different treatment eras, despite absolute mortality reductions. 3

The GRACE score demonstrates superior discrimination for in-hospital mortality (AUC 0.91) compared to other risk scores and outperforms subjective physician assessment. 1, 4

Integration with High-Sensitivity Troponin

High-sensitivity troponin 0/1-hour algorithms have higher sensitivity (78.1%) for detecting MI than any GRACE score threshold (range 23.8-66.5%). 5 However, combining GRACE scoring with hs-cTn testing provides complementary information: hs-cTn identifies MI presence while GRACE score determines ischemic risk and guides timing. 5

Supplementing the ESC 0/1-hour algorithm with GRACE risk scoring slightly increases MI detection but also increases false positives who would undergo potentially unnecessary early angiography. 5

Special Populations

Apply the same GRACE-based timing strategy in elderly patients (≥75 years) after careful evaluation of comorbidities, frailty, and life expectancy. 1 Elderly patients should be considered for invasive strategy with appropriate risk-benefit assessment. 1

In diabetic patients, use identical GRACE thresholds and timing as non-diabetic patients, as diabetes is already incorporated into the GRACE score calculation. 1