How do the TIMI (Thrombolysis In Myocardial Infarction) and GRACE (Global Registry of Acute Coronary Events) scores differ in risk assessment and clinical application for patients with acute coronary syndromes?

GRACE vs TIMI Risk Scores in Acute Coronary Syndromes

GRACE demonstrates superior predictive accuracy compared to TIMI for both in-hospital and long-term outcomes across all acute coronary syndrome presentations, with a C-statistic of 0.83 versus TIMI's lower discriminative ability. 1, 2

Key Differences in Predictive Performance

Discriminative Ability

• GRACE consistently outperforms TIMI with C-statistics of 0.83 for in-hospital death across STEMI, NSTEMI, and unstable angina populations, compared to TIMI's lower discriminative capacity 1, 3
• In NSTEMI patients specifically, GRACE shows significantly better prediction for both in-hospital events (AUC 0.82 vs 0.62) and long-term mortality (AUC 0.89 vs 0.68) 2
• For elderly female patients with NSTE-ACS, GRACE demonstrates superior accuracy with AUC of 0.79 versus TIMI's 0.68 for mortality prediction 4

Clinical Outcomes Predicted

• GRACE predicts mortality at multiple time points: in-hospital, 6-month, 1-year, and 3-year mortality or death/MI 1, 5
• TIMI predicts composite endpoints including 14-day all-cause death, MI, or urgent revascularization for NSTEMI/unstable angina, and 30-day mortality for STEMI 1, 6

Structural Differences Between Scores

GRACE Components (8 Variables)

• Uses weighted, semi-quantitative variables including age, Killip class, systolic blood pressure, heart rate, ST-segment deviation, cardiac arrest at presentation, serum creatinine, and positive cardiac biomarkers 1, 5
• Incorporates hemodynamic instability through Killip class (OR 2.0 per class) and cardiac arrest (OR 4.3) 5
• Accounts for renal function via serum creatinine (OR 1.2 per 1-mg/dL increase), which is particularly important as in-hospital mortality in STEMI patients with stage 4-5 chronic kidney disease approaches 30% 5

TIMI Components (7 Variables)

• Uses equally-weighted binary variables (1 point each): age ≥65 years, ≥3 CAD risk factors, known coronary stenosis ≥50%, ST-segment deviation ≥0.5mm, ≥2 anginal events in 24 hours, aspirin use in prior 7 days, and elevated cardiac biomarkers 1, 6
• Simpler bedside calculation without requiring computer assistance, with calculator available at www.timi.org 6

Risk Stratification Patterns

GRACE Risk Distribution

• Tends to classify more patients as high-risk: In one NSTEMI cohort, 45.7% were classified as high-risk by GRACE versus only 38.8% by TIMI 2
• High-risk threshold (>140-155) mandates aggressive therapy including early invasive strategy, intensive antiplatelet therapy, and close monitoring 1, 5

TIMI Risk Distribution

• Concentrates patients in intermediate-risk category: 61.2% of NSTEMI patients fall into medium risk (TIMI 3-4) 2
• Critical finding: Among TIMI medium-risk patients, 53.5% are actually GRACE high-risk (≥140), with significantly higher in-hospital events (39.5% vs 9.1%) and long-term mortality (22.2% vs 0%) 2

Guideline Recommendations

ACC/AHA Position

• GRACE is superior to subjective physician assessment for predicting death or MI in patients with STEMI or intermediate-risk NSTE-ACS 1
• Calculate GRACE score at admission for all confirmed ACS patients to predict short and long-term outcomes and guide intensity of therapy 1
• Both TIMI and GRACE are well-validated for guiding therapeutic decisions 1

ESC Position

• Recommends established risk scores with GRACE specifically considered for prognosis estimation 1

Clinical Application Algorithm

For NSTEMI/Unstable Angina

1. Calculate both TIMI and GRACE at presentation using readily available clinical data 1, 6
2. If TIMI is medium-risk (3-4), calculate GRACE to identify the 53.5% who are actually high-risk 2
3. GRACE ≥140 requires: Early invasive strategy within 24 hours, intensive antiplatelet therapy with glycoprotein IIb/IIIa inhibitors, and low-molecular-weight heparin 6, 5
4. TIMI ≥4 mandates: Early invasive strategy with coronary angiography and revascularization 6

For STEMI

• GRACE demonstrates excellent discriminative ability (C-statistic 0.83) for in-hospital and 6-month mortality 5
• TIMI shows similar discrimination (C-statistic 0.87) but better calibration in some STEMI populations 7
• Apply GRACE nomogram immediately at hospital admission to determine predicted mortality from discharge to 6 months 5

Critical Pitfalls to Avoid

The TIMI Medium-Risk Trap

• Do not assume TIMI medium-risk (3-4) is truly intermediate-risk: Over half of these patients are GRACE high-risk with 39.5% in-hospital event rates 2
• Always calculate GRACE for TIMI medium-risk patients to avoid underestimating true risk 2

Limitations in Undifferentiated Chest Pain

• Both scores perform poorly in patients with suspected but not proven ACS, with C-statistics barely better than age alone (GRACE 0.717 vs age 0.656) 8
• Use HEART score instead for emergency department evaluation of undifferentiated chest pain before ACS is confirmed 1

Calibration Considerations

• GRACE may overestimate risk in low-risk populations, showing inappropriate middle-range incidence (25% for intermediate-risk vs expected 4.9%) 7
• TIMI shows better calibration in some STEMI populations with satisfactory Hosmer-Lemeshow χ² = 1.4 (p=0.92) versus GRACE χ² = 14 (p=0.08) 7

Practical Implementation

GRACE Advantages

• Superior discrimination across all ACS types with consistent C-statistic of 0.83 1, 5
• Captures hemodynamic instability through Killip class and cardiac arrest 5
• Accounts for renal dysfunction, a critical mortality predictor 5
• Clinical application tool downloadable to handheld devices at www.outcomes-umassmed.org/grace 5

TIMI Advantages

• Simpler bedside calculation without computer assistance 6
• Better calibration in some populations, particularly STEMI 7
• Validated across multiple international trials including TIMI 11B and ESSENCE 6
• More convenient for rapid assessment with 7 equally-weighted binary variables 1

Sequential Use Strategy

• Start with TIMI for convenience at initial presentation 2
• Calculate GRACE for all TIMI medium-risk patients to identify hidden high-risk individuals 2
• Use GRACE for definitive risk stratification when determining intensity of therapy and timing of invasive strategy 1, 2