Prediction of mortality, bleeding, and ischaemic events in patients with cancer and acute coronary syndrome: a model development and validation study

Florian A Wenzl¹, Kok Weng Ow², Matthijs A Velders³, Freya Tyrer⁴, Lizz Paley⁵, Jennifer Lai⁵, Maria A Smolle⁶, Victor Schweiger⁷, Emil Hagström⁸, Mark A de Belder⁹, Peizhi Wang¹⁰, Antanas Gasys¹¹, Moa Simonsson¹², Clive Weston¹³, Davide Di Vece¹⁴, Christian Templin¹⁵, Hans Rickli¹⁶, Dragana Radovanovic¹⁷, Thomas M Suter¹⁸, Lorenz Räber¹¹, Michael D Peake¹⁹, John Deanfield²⁰, Stefan James⁸, David Adlam²¹, Thomas F Lüscher²²

Affiliations

¹ National Disease Registration Service, NHS England, London, UK; Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; Department of Clinical Sciences, Karolinska Institute, Stockholm, Sweden. Electronic address: florian.wenzl1@nhs.net.
² National Disease Registration Service, NHS England, London, UK; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
³ Department of Clinical Physiology, Västmanland County Hospital, Västerås, Sweden.
⁴ National Disease Registration Service, NHS England, London, UK; Department of Health Sciences, George Davies Centre, University of Leicester, Leicester, UK.
⁵ National Disease Registration Service, NHS England, London, UK.
⁶ Comprehensive Cancer Center Graz, Medical University of Graz, Graz, Austria.
⁷ Department of Cardiology, University Hospital Zurich, Zurich, Switzerland; Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Berlin, Germany.
⁸ Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
⁹ National Institute for Cardiovascular Outcomes Research, NHS Arden and Greater East Midlands Commissioning Support Unit, Leicester, UK.
¹⁰ Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Department of Cardiology, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
¹¹ Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland.
¹² Department of Medicine Solna, Karolinska Institute, Solna, Sweden.
¹³ Glangwili General Hospital, Carmarthen, UK.
¹⁴ Department of Cardiology and Internal Medicine B, University Medicine, Greifswald, Germany; German Centre for Cardiovascular Research (DZHK), Greifswald, Germany; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
¹⁵ Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Department of Cardiology and Internal Medicine B, University Medicine, Greifswald, Germany; German Centre for Cardiovascular Research (DZHK), Greifswald, Germany.
¹⁶ Cardiology Division, Kantonsspital St Gallen, St Gallen, Switzerland.
¹⁷ AMIS Plus Data Center, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
¹⁸ Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland; Lindenhofgruppe, Bern, Switzerland.
¹⁹ Glenfield Hospital, University of Leicester, Leicester, UK; Cancer Research UK, Oxford, UK.
²⁰ Institute of Cardiovascular Sciences, University College London, London, UK.
²¹ Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; Leicester British Heart Foundation Centre of Research Excellence, Leicester, UK; Leicester National Institute for Health and Care Research Biomedical Research Centre, Leicester, UK.
²² Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Heart Division, Royal Brompton and Harefield Hospitals, London, UK; National Heart and Lung Institute, Imperial College, London, UK; School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, UK.

PMID: 41620233
DOI: 10.1016/S0140-6736(25)02020-3

Free article

Prediction of mortality, bleeding, and ischaemic events in patients with cancer and acute coronary syndrome: a model development and validation study

Florian A Wenzl et al. Lancet. 2026.

Free article

. 2026 Jan 31;407(10527):515-528.

doi: 10.1016/S0140-6736(25)02020-3.

Authors

Affiliations

¹ National Disease Registration Service, NHS England, London, UK; Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; Department of Clinical Sciences, Karolinska Institute, Stockholm, Sweden. Electronic address: florian.wenzl1@nhs.net.
² National Disease Registration Service, NHS England, London, UK; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
³ Department of Clinical Physiology, Västmanland County Hospital, Västerås, Sweden.
⁴ National Disease Registration Service, NHS England, London, UK; Department of Health Sciences, George Davies Centre, University of Leicester, Leicester, UK.
⁵ National Disease Registration Service, NHS England, London, UK.
⁶ Comprehensive Cancer Center Graz, Medical University of Graz, Graz, Austria.
⁷ Department of Cardiology, University Hospital Zurich, Zurich, Switzerland; Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Berlin, Germany.
⁸ Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
⁹ National Institute for Cardiovascular Outcomes Research, NHS Arden and Greater East Midlands Commissioning Support Unit, Leicester, UK.
¹⁰ Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Department of Cardiology, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
¹¹ Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland.
¹² Department of Medicine Solna, Karolinska Institute, Solna, Sweden.
¹³ Glangwili General Hospital, Carmarthen, UK.
¹⁴ Department of Cardiology and Internal Medicine B, University Medicine, Greifswald, Germany; German Centre for Cardiovascular Research (DZHK), Greifswald, Germany; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
¹⁵ Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Department of Cardiology and Internal Medicine B, University Medicine, Greifswald, Germany; German Centre for Cardiovascular Research (DZHK), Greifswald, Germany.
¹⁶ Cardiology Division, Kantonsspital St Gallen, St Gallen, Switzerland.
¹⁷ AMIS Plus Data Center, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
¹⁸ Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland; Lindenhofgruppe, Bern, Switzerland.
¹⁹ Glenfield Hospital, University of Leicester, Leicester, UK; Cancer Research UK, Oxford, UK.
²⁰ Institute of Cardiovascular Sciences, University College London, London, UK.
²¹ Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; Leicester British Heart Foundation Centre of Research Excellence, Leicester, UK; Leicester National Institute for Health and Care Research Biomedical Research Centre, Leicester, UK.
²² Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Heart Division, Royal Brompton and Harefield Hospitals, London, UK; National Heart and Lung Institute, Imperial College, London, UK; School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, UK.

PMID: 41620233
DOI: 10.1016/S0140-6736(25)02020-3

Abstract

Background: Accurate assessment of mortality, bleeding, and atherothrombotic risk in patients with cancer and acute coronary syndrome could inform novel personalised treatment strategies, but no standardised tools for this purpose exist. We aimed to develop and validate a clinically applicable risk score for mortality, bleeding, and ischaemic events in patients with cancer and acute coronary syndrome.

Methods: In this model development and validation study, we obtained data for 1 017 759 patients who presented with acute coronary syndrome in England, UK (n=815 170; 36 771 with cancer), Sweden (n=194 059; 10 262 with cancer), and Switzerland (n=8530; 203 with cancer) between Jan 1, 2004, and Aug 8, 2023. Machine learning models were developed to predict all-cause mortality, major bleeding events, and ischaemic events, defined as a composite of cardiovascular death, myocardial infarction, and ischaemic stroke, in patients with cancer and acute coronary syndrome from England in a competing risks framework with a prediction horizon of 6 months. Final models (the ONCO-ACS score) were externally validated in geographically distinct held out datasets from the English Midlands, Sweden, and Switzerland.

Findings: Patients with cancer and with acute coronary syndrome were characterised by high rates of mortality (cumulative incidence 27·8% [95% CI 27·3-28·3]), major bleeding (7·3% [7·0-7·5]), and ischaemic events (16·1% [15·7-16·4]) and had a distinct risk profile. The ONCO-ACS score was informed by a single set of variables: tumour type, time since cancer diagnosis, metastatic disease, age, haemoglobin, heart rate, estimated glomerular filtration rate, BMI, Killip class, cardiac arrest, and major bleed within 6 months. Accounting for traditional and cancer-related risk factors, ONCO-ACS showed a time-dependent area under the receiver operating characteristic curve (tAUC) at 6 months of 0·84 (0·83-0·85) for all-cause mortality, 0·70 (0·68-0·73) for major bleeding, and 0·79 (0·78-0·81) for ischaemic events on internal validation. On external validation, ONCO-ACS achieved similar performance for all-cause mortality (tAUC at 6 months 0·84 [0·82-0·85] for the English Midlands, 0·80 [0·79-0·82] for Sweden, and 0·83 [0·76-0·91] for Switzerland), major bleeding events (0·70 [0·67-0·74] for the English Midlands, 0·67 [0·65-0·70] for Sweden, and 0·74 [0·57-0·91] for Switzerland), and ischaemic events (0·76 [0·74-0·78] for the English Midlands, 0·70 [0·69-0·72] for Sweden, and 0·73 [0·61-0·86] for Switzerland). ONCO-ACS was well calibrated and decision curve analyses suggested favourable clinical utility. Applying ONCO-ACS to current guidelines suggests that most patients with cancer and acute coronary syndrome qualify for invasive management and long dual antiplatelet therapy using clopidogrel.

Interpretation: The ONCO-ACS score provides a validated practical tool for predicting mortality, bleeding, and ischaemic risk in patients with cancer and acute coronary syndrome. Combined assessment of competing outcome risks could facilitate balancing treatment benefits and harms.

Funding: British Heart Foundation, Cancer Research UK, Swiss Heart Foundation, University of Zurich Foundation, Kurt-Senta-Herrmann Foundation, Theodor-Ida-Herzog-Egli Foundation, Foundation for Cardiovascular Research-Zurich Heart House, Swedish ALF Research Funds.

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Conflict of interest statement

Declaration of interests FAW reports financial support from the Fund for Fostering Young Scientists at the University of Zurich, the European Society of Cardiology, the Swiss Society of Cardiology, the Swiss Heart Foundation, the Medical University of Graz, Amgen Switzerland, 4TEEN4 Pharmaceuticals, PAM Theragnostics, and Sphingotec, all outside the submitted work; has received travel expenses for attending meetings from 4TEEN4 Pharmaceuticals, PAM Theragnostics, the European Society of Cardiology, the Swiss Society of Cardiology, the Zurich Heart House – Foundation for Cardiovascular Research and the Critical Care Clinical Trialists Workshop; has received support for biomarker measurement from Roche Diagnostics, 4TEEN4 Pharmaceuticals, PAM Theragnostics, and Sphingotec, outside of the submitted work; and reports membership in the ESC Digital Cardiology & AI Committee and the Steering Committee of the Swiss National Registry of Myocardial Infarction. KWO is a National Institute of Health and Care Research (NIHR) Academic Clinical Fellow in Cardiology and funded by the NIHR (ACF-2021-11-007). MAS reports travel expenses from Alphamed Fischer, Implantcast, ImplanTec, and PharmaMar, outside of the submitted work. EH has received institutional grants from Pfizer, NovoNordisk, and Amgen; honoraria for lectures by Amgen, NovoNordisk, AstraZeneca, and Bayer; has participated on the data safety monitoring board or advisory board of Amarin AB, NovoNordisk, Amgen, and Sanofi; is Chair of the Swedish Secondary Prevention Registry; and has leadership roles in the National Coordinator DalCore: CAL301 DalGene and R1500-CL-1643; Aegis II/Perfuse, outside of the submitted work. MS has received honoraria for lectures by Amgen, Boehringer Ingelheim, Novartis, and NovoNordisk; and has participated on an advisory board for AstraZeneca. CW has received honoraria for educational meetings from AstraZeneca; and is the Clinical Lead of the Myocardial Ischaemia National Audit Project registry. CT has received consulting fees from Biotronik, Medtronic, Microport, and Philips; declares honoraria for lectures from AstraZeneca, Boehringer Ingelheim, and Novartis; and has received payment for expert testimony by Microport, outside of the submitted work. LR has received grants from Abbott, Boston Scientific, Biotronik, Sanofi, Regeneron, Infraredx, and the Swiss National Science Foundation; reports consulting fees from Abbott, Amgen, Medtronic, NovoNordisk, Occlutech, and Sanofi; and has received honoraria for lectures from Abbott and Occlutech, outside of the submitted work. JD has received grants from Alzheimer's Research UK (2022–25) and the British Heart Foundation (2019–22); consulting fees from Amgen, AstraZeneca, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, NovoNordisk, and Bayer; and honoraria for lectures from Amgen, AstraZeneca, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, NovoNordisk, and Bayer, outside of the submitted work. SJ has received research grants from Janssen, AstraZeneca, Amgen, BMS, Novo Nordisk, Edwards, and Medtronic; consulting fees from Medtronic; and has participated in data safety monitoring boards or advisory boards for New Amsterdam, outside of the submitted work. DA has received research grants from Cancer Research UK and the British Heart Foundation for the submitted work; research grants from NIHR, Abbott Vascular, and Heart Research UK, outside of the submitted work; has received royalties from Elsevier, holds patents for a cardiac arrest device (EP3277337A1) and heart failure shunt device (patent application number 2211616.4); is member of the Phoenix study (NCT05825417); a member of the Advisory Board of Beat SCAD; and is Chair of the ESC-EORP SCAD Registry. TFL received institutional educational and research grants from Abbott, Ablative Solutions, Amgen, AstraZeneca, Boehringer Ingelheim, Daichi Sankyo, Novartis, Sanofi, Servier, and Vifor, outside the submitted work; has received consulting fees by Daichi Sankyo, Philips, Pfizer, and Ineeo; and honoraria from Amgen, Dacadoo, Daichi Sankyo, GlaxoSmithKline, Firalis, Menarini Foundation, NeuroImmune, and NovoNordisk, outside of the submitted work; and holds leadership positions at the European Society of Cardiology, the Swiss Heart Foundation, the Foundation for Cardiovascular Research—Zurich Heart House and the London Heart House. All other authors declare no competing interests.

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Prediction of mortality, bleeding, and ischaemic events in patients with cancer and acute coronary syndrome: a model development and validation study

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Prediction of mortality, bleeding, and ischaemic events in patients with cancer and acute coronary syndrome: a model development and validation study

Authors

Affiliations

Abstract

Conflict of interest statement

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