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

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.