Biomarker-Based Prediction of Recurrent Ischemic Events in Patients With Acute Coronary Syndromes

Gorav Batra; Johan Lindbäck; Richard C Becker; Robert A Harrington; Claes Held; Stefan K James; Tibor Kempf; Renato D Lopes; Kenneth W Mahaffey; Philippe Gabriel Steg; Robert F Storey; Eva Swahn; Kai C Wollert; Agneta Siegbahn; Lars Wallentin

doi:10.1016/j.jacc.2022.08.767

Biomarker-Based Prediction of Recurrent Ischemic Events in Patients With Acute Coronary Syndromes

J Am Coll Cardiol. 2022 Nov 1;80(18):1735-1747. doi: 10.1016/j.jacc.2022.08.767.

Authors

Affiliations

¹ Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. Electronic address: gorav.batra@ucr.uu.se.
² Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
³ Division of Cardiovascular Health and Disease, Heart, Lung and Vascular Institute, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
⁴ Department of Medicine, Stanford University, Stanford, California, USA.
⁵ Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
⁶ Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
⁷ Department of Medicine, Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA.
⁸ Stanford Center for Clinical Research, Department of Medicine, Stanford University, Stanford, California, USA.
⁹ Université de Paris, Institut National de la Santé et de la Recherche Médicale-Unité 1148, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France.
¹⁰ Department of Infection, Immunity and Cardiovascular Disease, University of Shefﬁeld, Shefﬁeld, United Kingdom.
¹¹ Department of Cardiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
¹² Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden; Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.

PMID: 36302586
DOI: 10.1016/j.jacc.2022.08.767

Abstract

Background: In patients with acute coronary syndrome (ACS), there is residual and variable risk of recurrent ischemic events.

Objectives: This study aimed to develop biomarker-based prediction models for 1-year risk of cardiovascular (CV) death and myocardial infarction (MI) in patients with ACS undergoing percutaneous coronary intervention.

Methods: We included 10,713 patients from the PLATO (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome) trial in the development cohort and externally validated in 3,508 patients from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial. Variables contributing to risk of CV death/MI were assessed using Cox regression models, and a score was derived using subsets of variables approximating the full model.

Results: There were 632 and 190 episodes of CV death/MI in the development and validation cohorts. The most important predictors of CV death/MI were the biomarkers, growth differentiation factor 15, and N-terminal pro-B-type natriuretic peptide, which had greater prognostic value than all candidate variables. The final model included 8 items: age (A), biomarkers (B) (growth differentiation factor 15 and N-terminal pro-B-type natriuretic peptide), and clinical variables (C) (extent of coronary artery disease, previous vascular disease, Killip class, ACS type, P2Y₁₂ inhibitor). The model, named ABC-ACS ischemia, was well calibrated and showed good discriminatory ability for 1-year risk of CV death/MI with C-indices of 0.71 and 0.72 in the development and validation cohorts, respectively. For CV death, the score performed better, with C-indices of 0.80 and 0.84 in the development and validation cohorts, respectively.

Conclusions: An 8-item score for the prediction of CV death/MI was developed and validated for patients with ACS undergoing percutaneous coronary intervention. The ABC-ACS ischemia score showed good calibration and discrimination and might be useful for risk prediction and decision support in patients with ACS. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872; Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER]; NCT00527943).

Keywords: acute coronary syndrome; biomarkers; cardiovascular death; percutaneous coronary intervention; risk score.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Acute Coronary Syndrome* / etiology
Biomarkers
Clopidogrel / therapeutic use
Growth Differentiation Factor 15
Humans
Myocardial Infarction* / etiology
Natriuretic Peptide, Brain
Percutaneous Coronary Intervention* / adverse effects
Platelet Aggregation Inhibitors / therapeutic use
Ticagrelor / therapeutic use
Treatment Outcome

Substances

Biomarkers
Clopidogrel
Growth Differentiation Factor 15
Natriuretic Peptide, Brain
Platelet Aggregation Inhibitors
Ticagrelor

Associated data

ClinicalTrials.gov/NCT00527943
ClinicalTrials.gov/NCT00391872