TIMI Risk Score — UA/NSTEMI 14-Day MACE
Seven binary factors — each present = 1 point. Predicts 14-day major adverse cardiac events.
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The TIMI Risk Score for Unstable Angina and Non-ST-Elevation Myocardial Infarction (UA/NSTEMI) is a validated, widely used clinical prediction tool that estimates the probability of major adverse cardiac events in patients presenting with acute coronary syndrome without persistent ST elevation. It was derived by Antman and colleagues from pooled data from the TIMI 11B and ESSENCE clinical trials, published in JAMA in 2000. The derivation cohort comprised 1,957 patients with UA/NSTEMI managed with enoxaparin or unfractionated heparin, and the score was subsequently validated in multiple independent prospective cohorts. The TIMI UA/NSTEMI score incorporates seven binary clinical variables — each contributing exactly 1 point when present — making it one of the simplest validated ACS risk tools to calculate at the bedside without laboratory values in some configurations. The seven variables are: age ≥ 65 years, presence of at least three traditional coronary artery disease risk factors, prior coronary stenosis ≥ 50% documented on angiography or by clinical history of obstructive CAD, ST-segment deviation on the presenting 12-lead ECG, at least two anginal events in the 24 hours preceding presentation, use of aspirin in the seven days prior to presentation, and elevation of serum cardiac markers (troponin or CK-MB) above the assay upper limit of normal. The composite primary endpoint predicted by the score is a 14-day all-cause death, new or recurrent myocardial infarction, or severe recurrent ischaemia requiring urgent revascularisation. This is a clinically meaningful 'hard endpoint' composite that captures the immediate danger period after NSTEMI or high-risk unstable angina. The risk across score tiers is approximately: 0–1 points = 4.7%, 2 points = 8.3%, 3 points = 13.2%, 4 points = 19.9%, 5 points = 26.2%, 6–7 points = 40.9%. These estimates have been broadly confirmed in external validation studies, though absolute rates vary with contemporary treatment strategies. The TIMI UA/NSTEMI score is endorsed in multiple ACS guidelines and remains one of the most commonly taught and applied risk scores in cardiology training worldwide.
TIMI UA/NSTEMI Score = sum of all applicable binary criteria (0 or 1 point each, maximum 7) 1. Age ≥ 65 years → 1 point 2. ≥ 3 Coronary Artery Disease (CAD) risk factors → 1 point (Risk factors: family history of premature CAD, hypertension, hypercholesterolaemia, diabetes mellitus, active smoking) 3. Prior coronary stenosis ≥ 50% (documented obstructive CAD) → 1 point (Prior MI, prior PCI/CABG, or known obstructive CAD on angiography) 4. ST-segment deviation on presenting ECG → 1 point (New horizontal or downsloping ST depression ≥ 0.5 mm, or transient ST elevation in ≥ 2 contiguous leads) 5. ≥ 2 anginal events in the prior 24 hours → 1 point (At least 2 distinct episodes of rest angina or angina with minimal exertion in the 24h before presentation) 6. Use of aspirin in the prior 7 days → 1 point (Aspirin use despite which the patient still developed ACS — a marker of more severe coronary disease and aspirin-refractory thrombosis) 7. Elevated serum cardiac markers → 1 point (Troponin I, troponin T, or CK-MB above the assay-specific 99th percentile upper limit of normal) Total score range: 0–7 points 14-day composite event risk (death, MI, urgent revascularisation): 0–1: ~4.7% | 2: ~8.3% | 3: ~13.2% | 4: ~19.9% | 5: ~26.2% | 6–7: ~40.9%
- 1Confirm the clinical diagnosis of UA/NSTEMI based on presenting symptoms (ischaemic chest pain, pressure, dyspnoea, or ACS equivalent), the absence of persistent ST elevation on the 12-lead ECG, and initial or serial cardiac biomarker measurements. Establish the onset time of symptoms and record all medications taken in the preceding 7 days, paying particular attention to aspirin use.
- 2Determine whether the patient is aged 65 years or older. If yes, assign 1 point. Age ≥ 65 is a continuous-variable surrogate in this dichotomised score, reflecting the well-established relationship between advancing age and higher rates of adverse cardiac events in ACS due to reduced physiological reserve, higher atherosclerotic burden, and more impaired coronary microcirculation.
- 3Systematically document coronary artery disease risk factors: family history of premature CAD (first-degree relative with MI or coronary revascularisation before age 55 in men or 65 in women), hypertension (diagnosed or on antihypertensive medication), hypercholesterolaemia (diagnosed or on lipid-lowering therapy), diabetes mellitus (type 1 or type 2), and current or recent cigarette smoking. Score 1 point if three or more of these risk factors are present. Note: prior documented CAD (next criterion) is scored separately.
- 4Assess whether the patient has documented prior coronary stenosis of ≥ 50% based on any previous coronary angiogram, or infer from clinical history of prior myocardial infarction, prior PCI (stenting), or prior coronary artery bypass graft surgery (CABG). This criterion identifies patients with established obstructive coronary artery disease at substantially higher risk for recurrent events compared with those with a first-time presentation. Score 1 point if present.
- 5Review the presenting 12-lead ECG carefully, comparing with any available prior tracings. Score 1 point if there is new ST-segment deviation: new horizontal or downsloping ST depression ≥ 0.5 mm in ≥ 2 contiguous leads, or transient ST elevation (not persistent, which would reclassify the patient as STEMI). New T-wave inversions alone, while prognostically relevant, do not formally meet this criterion in the original score derivation, though some clinical implementations include them.
- 6Obtain a focused ischaemic event history for the 24 hours preceding presentation. Score 1 point if the patient reports two or more distinct episodes of ischaemic discomfort (chest pain, pressure, dyspnoea, or equivalent) occurring at rest or with minimal exertion in that timeframe. Crescendo pattern of angina (increasing frequency, duration, or severity) with multiple daily episodes is a classic high-risk UA presentation. Carefully distinguish cardiac ischaemic events from musculoskeletal or pleuritic discomfort.
- 7Record aspirin use in the prior 7 days and assess cardiac biomarkers. If the patient was already taking aspirin regularly and still developed ACS, score 1 point — this criterion is counterintuitive but identifies a phenotype of aspirin-refractory thrombosis and more severe coronary disease. For cardiac markers, score 1 point if any troponin (I or T) or CK-MB is elevated above the assay-specific 99th percentile upper limit of normal on the presenting or serial sample. Use high-sensitivity troponin assays where available. Sum all seven criteria to obtain the TIMI UA/NSTEMI score and apply the 14-day composite risk estimate.
Low risk — serial troponin and ECG monitoring; outpatient follow-up with stress testing may be appropriate
This 42-year-old male scores 0 on all seven TIMI UA/NSTEMI criteria: he is under 65, has only 2 CAD risk factors (not 3), no documented prior stenosis, no ST changes, only one anginal episode, was not on aspirin, and has a negative troponin. A TIMI UA/NSTEMI score of 0 corresponds to approximately 4.7% 14-day composite event risk. While this is the lowest TIMI tier, it does not mean the patient can be immediately discharged — serial high-sensitivity troponin at 0h and 1–3h is essential to rule out NSTEMI, and non-invasive stress testing is warranted given the two CAD risk factors and ischaemic-type symptoms.
Very high risk — early invasive strategy within 24h; cardiology activation
Despite being only 61 (scoring 0 for age), this patient accumulates 6 of 7 points: ≥3 risk factors (1 pt) + prior stenosis/PCI (1 pt) + ST depression (1 pt) + ≥2 anginal episodes (1 pt) + aspirin use (1 pt) + elevated troponin (1 pt) = 6 points. A score of 6 places him in the highest TIMI tier at approximately 40.9% 14-day composite event risk. Per ESC and ACC/AHA NSTEMI guidelines, this high-risk profile warrants early invasive coronary angiography within 24 hours, intensified antithrombotic therapy (ticagrelor or prasugrel preferred over clopidogrel), and ICU-level monitoring.
Very high risk — transient ST elevation may indicate critical proximal lesion or vasospasm; urgent angiography
This 72-year-old woman scores 6 points: age ≥ 65 (1 pt) + ≥3 risk factors (1 pt) + ECG deviation (transient ST elevation — 1 pt) + ≥2 anginal events (1 pt) + aspirin use (1 pt) + elevated troponin (1 pt) = 6 points. No prior stenosis documentation reduces the score by 1. The transient ST elevation pattern raises suspicion for critical proximal LAD or LM disease or vasospastic angina and warrants particular urgency. Her very high TIMI score combined with transient ST elevation meets ESC very-high-risk criteria, supporting immediate (< 2h) invasive strategy.
Intermediate risk — admit for serial troponin; non-invasive or invasive workup based on evolving biomarkers
This 67-year-old woman scores 3 points: age ≥ 65 (1 pt) + ≥2 anginal events (1 pt) + aspirin use (1 pt) = 3 points. Her two CAD risk factors do not reach the threshold of 3, she has no prior documented stenosis, no ECG changes, and a negative initial troponin. A score of 3 corresponds to approximately 13.2% 14-day composite event risk — intermediate risk. Serial high-sensitivity troponin at 1–3 hours is essential; if negative, stress testing or CT coronary angiography is appropriate to exclude obstructive CAD before discharge. If troponin becomes positive, the score rises to 4 (19.9% risk) and the management pathway shifts toward early invasive strategy.
Rapid bedside risk stratification of UA/NSTEMI patients in the emergency department before laboratory results are fully available — six of seven criteria can be assessed from history and ECG alone within 15 minutes of initial assessment, enabling early triage decisions
Guiding antithrombotic therapy intensity in NSTEMI — high TIMI scores (≥4) support use of potent P2Y12 inhibitors (ticagrelor or prasugrel) over clopidogrel, and may prompt addition of anticoagulants such as enoxaparin or bivalirudin, consistent with ACS guideline recommendations
Patient and family prognostic communication — translating a TIMI score into a percentage 14-day risk estimate (e.g., 'your risk of a serious cardiac event in the next 14 days is approximately 20%') enables informed consent for invasive procedures and realistic prognostic discussions
Determining timing of coronary angiography — higher TIMI scores support early invasive strategy (within 24–72h) over selective invasive approach, though ESC guidelines now preferentially use GRACE 2.0 for this specific decision; TIMI serves as a complementary rapid screen
Medical education and NSTEMI training — the TIMI UA/NSTEMI score is the most widely taught ACS risk score in medical schools and cardiology training programmes worldwide due to its simplicity, binary structure, and memorable seven-criterion format, making it an effective framework for teaching risk stratification principles
MINOCA — MI with non-obstructive coronary arteries
Approximately 5–10% of patients presenting with NSTEMI are found to have no obstructive coronary artery disease (stenosis < 50%) on angiography, a condition termed MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries). These patients typically score lower on TIMI UA/NSTEMI (no prior stenosis criterion, often fewer CAD risk factors) yet have significant underlying pathology including myocarditis, Takotsubo syndrome, coronary vasospasm, coronary thromboembolism, or plaque erosion. A low TIMI score in a troponin-positive patient with atypical features for obstructive CAD should prompt consideration of MINOCA, CMR imaging post-angiography, and specialist workup rather than reassurance of low risk.
Aspirin criterion — clarifying its paradoxical scoring logic
The aspirin criterion in the TIMI UA/NSTEMI score is one of the most frequently misunderstood elements of the tool. It does not indicate that aspirin increases cardiac risk. The criterion was statistically derived: in the original TIMI 11B and ESSENCE trial populations, patients already taking aspirin had a higher background event rate because aspirin use was a proxy for known coronary artery disease severity and chronic cardiovascular risk. In modern practice, virtually all patients with confirmed CAD are prescribed aspirin, so this criterion is increasingly omnipresent and may slightly inflate TIMI scores compared with the original derivation cohort. Clinicians should not interpret the aspirin criterion as a reason to withhold or avoid aspirin therapy.
Elevated markers — high-sensitivity troponin and the diagnostic threshold
The original TIMI UA/NSTEMI score was derived when conventional troponin assays required 6–12 hours to become positive. High-sensitivity troponin (hs-Tn) assays, now standard in most developed healthcare systems, detect troponin elevations within 1–2 hours of symptom onset with greater sensitivity. The troponin criterion in TIMI should always use the assay-specific 99th percentile sex-specific upper limit of normal with the hs-Tn assay. Women have lower hs-Tn ULN values, and applying a unisex threshold systematically under-detects NSTEMI in women. A rising delta troponin over serial measurements also meets the criterion if either value exceeds the ULN.
Three or more CAD risk factors — precise definition matters
The ≥3 CAD risk factors criterion in the TIMI UA/NSTEMI score uses the following specific five risk factors in the original derivation: family history of premature CAD, hypertension, hypercholesterolaemia, diabetes mellitus, and current smoking. Notably, age, sex, renal disease, and obesity are NOT included in this specific TIMI criterion (though they are independent cardiovascular risk factors). Clinicians sometimes incorrectly include non-traditional risk factors or miscount, either over- or under-scoring this criterion. It is also important to note that prior documented coronary stenosis ≥ 50% is a separate criterion scored independently — it does not count as one of the 'three risk factors.'
TIMI UA/NSTEMI score limitations in the high-sensitivity troponin era
The TIMI UA/NSTEMI score was derived in the late 1990s before high-sensitivity troponin assays, CT coronary angiography, and potent P2Y12 inhibitors (ticagrelor, prasugrel) became standard of care. Contemporary external validation studies show that the score has moderate discriminative ability (C-statistic ~0.65) compared with GRACE 2.0 (~0.83). ESC 2020 NSTEMI/UA guidelines now preferentially cite GRACE score over TIMI for guiding invasive strategy timing. TIMI UA/NSTEMI retains its value as a rapid, easily memorised bedside screening tool and in settings where serum creatinine or echocardiographic Killip assessment is not immediately available, but should not be the sole criterion for major clinical decisions in centres with access to GRACE calculators.
| Score | Risk Tier | 14-Day Event Risk* | Recommended Management |
|---|---|---|---|
| 0–1 | Very Low | ~4.7% | Serial troponin; selective non-invasive workup; consider early discharge with outpatient follow-up |
| 2 | Low | ~8.3% | Admit for monitoring; serial hs-troponin; non-invasive stress testing or CTCA before discharge |
| 3 | Intermediate | ~13.2% | Admit; DAPT + anticoagulation; invasive workup within 72h or non-invasive testing if biomarkers remain negative |
| 4 | Intermediate-High | ~19.9% | Early invasive angiography within 24–72h; ticagrelor or prasugrel; LMWH anticoagulation |
| 5 | High | ~26.2% | Early invasive within 24h; cardiology review; intensified antithrombotic; HDU/ICU monitoring |
| 6–7 | Very High | ~40.9% | Early or immediate invasive strategy; potential very-high-risk features assessment; ICU-level care |
What composite endpoint does the TIMI UA/NSTEMI score predict?
The TIMI UA/NSTEMI score predicts the 14-day risk of a composite endpoint comprising three components: all-cause death, new or recurrent myocardial infarction (including non-fatal MI requiring re-hospitalisation), and severe recurrent ischaemia requiring urgent revascularisation (defined as either urgent PCI or CABG precipitated by haemodynamic instability or refractory ischaemia). This composite captures the full spectrum of serious short-term cardiac events following NSTEMI or high-risk unstable angina. The score does not directly predict isolated MI or revascularisation separately — it is the combined endpoint that maps to the published risk percentages.
Why does aspirin use score a positive point — does taking aspirin make the outcome worse?
The aspirin criterion is counterintuitive at first glance. Scoring 1 point for aspirin use in the prior 7 days does not mean aspirin causes harm. Rather, the criterion identifies a clinically important phenotype: patients who develop ACS despite already being on aspirin antiplatelet therapy ('aspirin-refractory' thrombosis). These patients tend to have more advanced coronary artery disease, higher-risk plaque biology (thrombus forming despite aspirin-mediated COX-1 inhibition), and a greater need for additional antithrombotic therapy such as P2Y12 inhibitors. In the original TIMI 11B cohort, aspirin use prior to presentation was statistically associated with higher event rates because it identified patients with known or more severe coronary artery disease who were already on secondary prevention.
How does the TIMI UA/NSTEMI score compare to GRACE and HEART scores?
These three scores serve different clinical functions. The TIMI UA/NSTEMI score is a rapid bedside tool using 7 binary variables to estimate 14-day composite event risk in confirmed or strongly suspected NSTEMI/UA. GRACE 2.0 is a more complex multivariate model using continuous variables (age, HR, SBP, creatinine, Killip class) that predicts in-hospital and 6-month all-cause mortality with superior discriminative accuracy (higher C-statistic of ~0.83 vs ~0.65 for TIMI), and is the preferred score in ESC guidelines for NSTEMI risk stratification and invasive strategy timing. The HEART Score is designed for undifferentiated ED chest pain (not confirmed NSTEMI) and predicts 6-week MACE. In contemporary practice, GRACE 2.0 is preferred over TIMI for NSTEMI risk stratification, while TIMI remains valuable for rapid bedside assessment and in settings where serum creatinine is not yet available.
What defines 'prior coronary stenosis ≥ 50%' in clinical practice?
Prior coronary stenosis ≥ 50% is considered present if any of the following is documented: (1) prior coronary angiography showing ≥ 50% diameter stenosis in any epicardial vessel; (2) prior myocardial infarction (established obstructive CAD); (3) prior percutaneous coronary intervention (PCI/stenting), indicating pre-existing significant stenosis that required treatment; or (4) prior coronary artery bypass graft surgery (CABG), confirming obstructive multi-vessel CAD. In practice, a clinical history of any of these four conditions is sufficient to score this criterion as positive without access to prior angiographic reports. The criterion captures patients with established coronary artery disease who are at substantially higher risk for recurrent acute events than those with a first-ever presentation.
Should the TIMI UA/NSTEMI score be used in patients with confirmed STEMI?
No. The TIMI UA/NSTEMI score was derived specifically from UA/NSTEMI patients and should only be applied to patients without persistent ST elevation. For STEMI patients, the TIMI STEMI Risk Score — a completely separate tool with different variables, point weightings, and endpoint (30-day mortality rather than 14-day composite) — should be used if risk stratification is desired. Applying the NSTEMI score to STEMI patients would be methodologically incorrect and clinically misleading, as the variables and predicted outcomes are fundamentally different.
What is the appropriate clinical action for each TIMI UA/NSTEMI risk tier?
Scores 0–1 (4.7% risk): serial troponin monitoring, outpatient or short-stay observation management, non-invasive stress testing or CT coronary angiography before discharge, selective invasive strategy if non-invasive testing suggests significant ischaemia. Scores 2–3 (8–13% risk): admission for monitoring, serial high-sensitivity troponin, consideration of non-invasive or invasive workup based on clinical trajectory; low-molecular-weight heparin and dual antiplatelet therapy. Scores 4–5 (20–26% risk): early invasive angiography within 24–72h, potent P2Y12 inhibitor (ticagrelor or prasugrel), anticoagulation, cardiology supervision. Scores 6–7 (41% risk): high-risk NSTEMI pathway, early invasive strategy within 24h, consider ICU-level monitoring, intensified antithrombotic regimen, and evaluation for very-high-risk features (haemodynamic instability, troponin surge, recurrent ischaemia) that may trigger immediate (<2h) angiography.
Does the TIMI UA/NSTEMI score perform differently in women?
Women with NSTEMI and unstable angina have historically been under-diagnosed and under-treated relative to men. The TIMI UA/NSTEMI score was derived in a cohort where women represented approximately 34% of patients, so it applies to both sexes. However, women are more likely to have non-obstructive coronary artery disease (MINOCA) and more atypical symptoms, which may affect the accuracy of the clinical history component. The troponin criterion should apply sex-specific thresholds when high-sensitivity assays are used (women have lower 99th percentile ULN values). Additionally, women with UA/NSTEMI are less likely to have prior documented stenosis and less likely to be on aspirin at presentation, which may result in somewhat lower TIMI scores despite similar or higher absolute event risk in some subgroups.
Can the TIMI UA/NSTEMI score be calculated before troponin results are available?
Yes, partially. Six of the seven TIMI UA/NSTEMI criteria (age, risk factors, prior stenosis, ECG deviation, anginal frequency, aspirin use) can be assessed immediately from history and ECG without waiting for laboratory results. The score can be provisionally calculated using these six criteria to provide initial risk stratification while awaiting biomarkers. However, the troponin criterion (1 point) is important for definitively classifying NSTEMI versus unstable angina and should be incorporated as soon as results are available. With high-sensitivity troponin assays enabling results within 30–60 minutes of blood draw, the wait is brief and the complete 7-criterion score can usually be finalised within the first hour of assessment.
プロのヒント
Use the TIMI UA/NSTEMI score as a rapid initial stratification tool at first presentation, then refine the risk assessment using GRACE 2.0 once all laboratory values (especially serum creatinine for Killip and haemodynamic variables) are available. In contemporary practice, GRACE 2.0 provides better discriminative accuracy and maps directly to ESC guideline-recommended invasive strategy timing (immediate, early, or selective). The TIMI score's main advantage is speed — it can be calculated entirely from history and ECG while awaiting laboratory results, enabling an initial management decision within the first 15 minutes of assessment.
ご存知でしたか？
The TIMI UA/NSTEMI score emerged from the TIMI 11B trial — one of the first large randomised trials to demonstrate that low-molecular-weight heparin (enoxaparin) was superior to unfractionated heparin in reducing recurrent events in NSTEMI. The risk score was essentially a by-product of the trial's statistical analysis: while the primary aim was to compare two anticoagulants, Antman and colleagues noticed that certain baseline variables predicted outcomes so strongly that they warranted formalisation as a clinical prediction tool. Published in JAMA in 2000, it has since accumulated over 10,000 citations — making it one of the most cited cardiology papers of the 21st century — despite being derived from fewer than 2,000 patients.
参考文献
- ›Antman EM et al. The TIMI Risk Score for Unstable Angina/Non–ST Elevation MI: A Method for Prognostication and Therapeutic Decision Making — JAMA 2000
- ›Collet JP et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation — Eur Heart J 2021
- ›Amsterdam EA et al. 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes — J Am Coll Cardiol 2014
- ›Pollack CV et al. 2006 Canadian Cardiovascular Society Guidelines for the Diagnosis and Management of Stable Angina — Can J Cardiol 2006
- ›Morrow DA et al. TIMI Risk Score for ST-Elevation Myocardial Infarction: A Convenient, Bedside, Clinical Score for Risk Assessment at Presentation — Circulation 2000