What is the preferred risk stratification score, TIMI (Thrombolysis In Myocardial Infarction) vs Killip vs GRACE (Global Registry of Acute Coronary Events), in managing Non-ST-Elevation Myocardial Infarction (NSTEMI)?

Risk Stratification in NSTEMI: GRACE Score is Superior

The GRACE risk score should be the preferred risk stratification tool for NSTEMI patients, as it demonstrates superior predictive accuracy compared to TIMI and incorporates Killip class as one of its variables. 1

Why GRACE Outperforms TIMI

The most recent 2025 ACC/AHA guidelines explicitly state that GRACE risk assessment has been found superior to subjective physician assessment for predicting death or MI in patients with STEMI or intermediate-risk NSTE-ACS, while both GRACE and TIMI scores are well-validated and may be useful for guiding therapeutic decisions. 1 The 2020 ESC guidelines similarly recommend using established risk scores with GRACE specifically considered for prognosis estimation. 1

Predictive Performance

• GRACE demonstrates better discriminative ability with a C-statistic of 0.83 for predicting in-hospital death across STEMI, NSTEMI, and unstable angina populations 1
• Recent research from East Asian NSTEMI patients showed GRACE significantly outperformed TIMI for both in-hospital events (AUC 0.82 vs 0.62) and long-term mortality (AUC 0.89 vs 0.68) 2
• A Chinese multicenter registry of 5,896 NSTEMI patients confirmed GRACE's superior predictive accuracy (AUC 0.79) compared to TIMI (AUC 0.56) for in-hospital mortality 3

Understanding Each Score's Role

GRACE Risk Score Components

The GRACE model uses 8 variables that capture both hemodynamic instability and underlying disease severity 1:

• Age (OR 1.7 per 10 years)
• Killip class (OR 2.0 per class) - this directly addresses your question about Killip classification
• Systolic blood pressure (OR 1.4 per 20 mmHg decrease)
• Heart rate (OR 1.3 per 30 bpm increase)
• ST-segment deviation (OR 2.4)
• Cardiac arrest at presentation (OR 4.3)
• Serum creatinine (OR 1.2 per 1 mg/dL increase)
• Positive cardiac biomarkers (OR 1.6)

TIMI Risk Score Components

The TIMI score uses 7 equally-weighted variables (1 point each) 1:

• Age ≥65 years
• ≥3 CAD risk factors
• Known coronary stenosis ≥50%
• ST-segment deviation ≥0.5 mm
• ≥2 anginal events in prior 24 hours
• Aspirin use in prior 7 days
• Elevated cardiac biomarkers

Killip Classification

Killip class is not a standalone risk score but rather a component of the GRACE score that classifies heart failure severity 1:

• Class I: No heart failure
• Class II: Rales, S3 gallop, or elevated JVP
• Class III: Pulmonary edema
• Class IV: Cardiogenic shock

Practical Clinical Algorithm

Step 1: Calculate GRACE Score at Admission

Use the GRACE 2.0 calculator (available at www.outcomes-umassmed.org/grace) to predict in-hospital, 6-month, 1-year, and 3-year mortality or death/MI 1

Step 2: Risk Stratification for Treatment Intensity

• GRACE >140 = High Risk: Requires aggressive therapy including early invasive strategy, intensive antiplatelet therapy, and close monitoring 4
• GRACE ≤140 = Lower Risk: May allow more conservative initial approach 4

Step 3: Identify Highest Risk Patients

Patients with GRACE >140 AND left ventricular ejection fraction <35% have the highest risk with 9.2% probability of in-hospital life-threatening ventricular arrhythmias and 23% mortality 4

Step 4: Consider Sequential Scoring for Convenience

If you need a simpler bedside tool initially, calculate TIMI first, then apply GRACE to TIMI intermediate-risk patients 2:

• Among TIMI medium-risk patients (score 3-4), those with GRACE ≥140 had significantly higher in-hospital events (39.5% vs 9.1%) and 4-year mortality (22.2% vs 0%) compared to GRACE <140 2
• This sequential approach preserves convenience while maintaining predictive accuracy 2

Critical Pitfalls to Avoid

Do not use risk scores as diagnostic tools - they stratify risk only in suspected or confirmed ACS, not for diagnosis 1

Do not rely on TIMI alone for mortality prediction - while TIMI predicts the composite endpoint of death/MI/urgent revascularization at 14 days, GRACE specifically targets mortality and performs better 1, 2, 3

Do not ignore renal function - GRACE incorporates creatinine while TIMI does not, and renal impairment significantly increases both short- and long-term mortality risk in ACS 1

Recognize that higher risk scores identify patients who benefit most from aggressive therapy - there is progressively greater benefit from GP IIb/IIIa inhibitors, LMWH, and early invasive strategy with increasing GRACE scores 1

Evidence Limitations

While GRACE demonstrates superior predictive accuracy, there is insufficient evidence that routine use of risk scores translates into reduced cardiovascular events 1. The Australian GRACE Risk Score Intervention Study (AGRIS) failed to demonstrate added value with routine GRACE implementation, largely because control hospitals performed better than expected 1. However, this does not negate GRACE's superior discriminative ability for identifying high-risk patients who warrant intensive monitoring and treatment.