TIMI, GRACE and alternative risk scores in Acute Coronary Syndromes: A meta-analysis of 40 derivation studies on 216,552 patients and of 42 validation studies on 31,625 patients

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Abstract

Background

Acute coronary syndromes (ACS) represent a difficult challenge for physicians. Risk scores have become the cornerstone in clinical and interventional decision making.

Methods and results

PubMed was systematically searched for ACS risk score studies. They were divided into ACS studies (evaluating Unstable Angina; UA, Non ST Segment Elevation Myocardial Infarction; NSTEMI, and ST Segment Elevation Myocardial Infarction; STEMI), UA/NSTEMI studies or STEMI studies. The c-statistics of validation studies were pooled when appropriate with random-effect methods. 7 derivation studies with 25,525 ACS patients and 15 validation studies including 257,654 people were formally appraised. Pooled analysis of GRACE scores, both at short (0.82; 0.80–0.89 I.C 95%) and long term follow up (0.84; 0.82–0.87; I.C 95%) showed the best performance, with similar results to Simple Risk Index (SRI) derivation cohorts at short term. For NSTEMI/UA, 18 derivation studies with 56,560 patients and 18 validation cohorts with 56,673 patients were included. Pooled analysis of validations studies showed c-statistics of 0.54 (95% CI = 0.52–0.57) and 0.67 (95% CI = 0.62–0.71) for short and long term TIMI validation studies, and 0.83 (95% CI = 0.79–9.87) and 0.80 (95% CI = 0.74–0.89) for short and long term GRACE studies. For STEMI, 15 studies with 134,557 patients with derivation scores, and 17 validation studies with 187,619 patients showed a pooled c-statistic of 0.77 (95% CI = 0.71–0.83) and 0.77 (95% CI = 0.72–0.85) for TIMI at short and long term, and a pooled c-statistic of 0.82 (95% CI = 0.81–0.83) and 0.81 (95% CI = 0.80–0.82) for GRACE at short and long terms respectively.

Conclusions

TIMI and GRACE are the risk scores that up until now have been most extensively investigated, with GRACE performing better. There are other potentially useful ACS risk scores available however these have not undergone rigorous validation. This study suggests that these other scores may be potentially useful and should be further researched.

Introduction

Acute coronary syndromes (ACS) represent a wide clinical spectrum, ranging from unstable angina (UA) to ST Elevation Myocardial infarction (STEMI). There is heterogeneity of diagnosis, treatment, and prognosis at different ends of this ACS spectrum [1], [2].

The use and development of dedicated scores to discriminate patients at high risk of serious adverse events from low risk ones has been suggested and encouraged by many cardiology expert groups in order to allow accurate therapeutic and diagnostic decision making. [3] Risk assessment remains crucial as the benefits of more aggressive and costly treatments are greatest in patients at higher risk of adverse clinical events [4], [5], [6].

Much effort has therefore been put into designing risk scores for ACS patients. The two most commonly used being the Global Registry in Acute Coronary Events (GRACE) [4] and the Thrombolysis in Myocardial Infarction (TIMI) [7] scores. Both are derived from landmark ACS studies and have undergone wide prospective evaluation. More recently other scores have been designed to focus on clinical risk assessment and to improve the selection of patients for clinical and interventional procedures.

Despite the presence of many validation studies confirming the validity of GRACE and TIMI in multiple clinical settings, to our knowledge there has been no meta-analysis to systematically compare their discriminatory performance. We therefore aimed to undertake a systematic review to assess ACS risk evaluation scores in order to determine the most accurately performing.

Section snippets

Methods

Current guidelines, including the recent Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) amendment to the Quality of Reporting of Meta-analyses (QUOROM) statement, as well as recommendations from The Cochrane Collaboration and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) were followed during the course of this work [6], [7], [8], [9], [10].

Results

Data search and study selection are summarized in Fig. 1.

Discussion

The most important findings of our meta-analysis are: a) There is a striking difference in the rates of patients undergoing invasive revascularization between derivation and validation studies, b) TIMI and GRACE risk scores are the only scores which have been validated in all types of ACS, with the GRACE score performing better, c) many other risk scores, which show good performance in a derivation cohort, have not yet been evaluated in validation cohorts.

Derivation and validation studies

Conclusions

TIMI and GRACE are the risk scores that up until now have been most extensively investigated, with GRACE performing better. There are other potentially useful ACS risk scores available however these have not undergone rigorous validation. This study suggests that these other scores may be potentially useful and should be further researched.

Disclosures

None.

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