1. Sex-specific evaluation and redevelopment of the GRACE score in non-ST-segment elevation acute coronary syndromes in populations from the UK and Switzerland: a multinational analysis with external cohort validation.
- Author
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Wenzl FA, Kraler S, Ambler G, Weston C, Herzog SA, Räber L, Muller O, Camici GG, Roffi M, Rickli H, Fox KAA, de Belder M, Radovanovic D, Deanfield J, and Lüscher TF
- Subjects
- Female, Hospital Mortality, Humans, Male, Prognosis, Registries, Risk Assessment, Switzerland epidemiology, United Kingdom, Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome therapy
- Abstract
Background: The Global Registry of Acute Coronary Events (GRACE) 2.0 score was developed and validated in predominantly male patient populations. We aimed to assess its sex-specific performance in non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and to develop an improved score (GRACE 3.0) that accounts for sex differences in disease characteristics., Methods: We evaluated the GRACE 2.0 score in 420 781 consecutive patients with NSTE-ACS in contemporary nationwide cohorts from the UK and Switzerland. Machine learning models to predict in-hospital mortality were informed by the GRACE variables and developed in sex-disaggregated data from 386 591 patients from England, Wales, and Northern Ireland (split into a training cohort of 309 083 [80·0%] patients and a validation cohort of 77 508 [20·0%] patients). External validation of the GRACE 3.0 score was done in 20 727 patients from Switzerland., Findings: Between Jan 1, 2005, and Aug 27, 2020, 400 054 patients with NSTE-ACS in the UK and 20 727 patients with NSTE-ACS in Switzerland were included in the study. Discrimination of in-hospital death by the GRACE 2.0 score was good in male patients (area under the receiver operating characteristic curve [AUC] 0·86, 95% CI 0·86-0·86) and notably lower in female patients (0·82, 95% CI 0·81-0·82; p<0·0001). The GRACE 2.0 score underestimated in-hospital mortality risk in female patients, favouring their incorrect stratification to the low-to-intermediate risk group, for which the score does not indicate early invasive treatment. Accounting for sex differences, GRACE 3.0 showed superior discrimination and good calibration with an AUC of 0·91 (95% CI 0·89-0·92) in male patients and 0·87 (95% CI 0·84-0·89) in female patients in an external cohort validation. GRACE 3·0 led to a clinically relevant reclassification of female patients to the high-risk group., Interpretation: The GRACE 2.0 score has limited discriminatory performance and underestimates in-hospital mortality in female patients with NSTE-ACS. The GRACE 3.0 score performs better in men and women and reduces sex inequalities in risk stratification., Funding: Swiss National Science Foundation, Swiss Heart Foundation, Lindenhof Foundation, Foundation for Cardiovascular Research, and Theodor-Ida-Herzog-Egli Foundation., Competing Interests: Declaration of interests SK received travel support from the European Atherosclerosis Society and equipment and materials from Roche Diagnostics, outside the submitted work. MR declares institutional research grants from Terumo, Biotronik, Medtronic, Cordis/Cardinal Health, and Boston Scientific, outside the submitted work. LR received funding from Abbott, Biotronik, Boston Scientific, Sanofi, Regeneron, and Heartflow, consulting fees from Abbott, Amgen, AstraZeneca, Canon, NovoNordisk, Medtronic, Sanofi, Occlutech, and Vifor, payment or honoraria from Abbott and Occlutech, and travel support from AstraZeneca. MdB is Chair of the Data Monitoring and Ethics Committee of the UK GRIS Trial and part of the Steering Committee of the DAPA MI Trial. CW is the clinical lead of the MINAP registry. JD received consulting fees from GENinCode UK Ltd, honoraria or consulting fees from Amgen, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, Novo Nordisk, and Bayer, and travel support from the Einstein Professorship Foundation (Berlin, Germany), outside the submitted work. JD holds unpaid leadership positions at Our Future Health and Public Health England. TFL declares institutional educational and research grants from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Daichi Sankyo, Novartis, and Vifor, and consulting fees from Daichi Sankyo, Philipps, Pfizer, and Ineeo Inc, outside the submitted work. TFL holds leadership positions at the European Society of Cardiology, Swiss Heart Foundation, and the Foundation for Cardiovascular Research—Zurich Heart House. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
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