Developing and validating the CE-MACE model to predict 1-year major adverse cardiovascular events post-COPD exacerbation using routine healthcare data

Background Patients with COPD are at an elevated risk of cardiovascular events, particularly following acute exacerbations. Existing prediction models underestimate their risk. We developed and validated the CE-MACE model to predict 1-year major adverse cardiovascular event (MACE) risk following a COPD exacerbation. Methods Using electronic health records from the UK Clinical Practice Research Datalink Aurum database, we included patients ≥40 years old with moderate or severe COPD exacerbations. The outcome was fatal or non-fatal MACE (acute coronary syndrome, arrhythmia, heart failure or ischaemic stroke). Cause-specific hazard models were used to estimate the coefficient of predictors. Model performance was assessed by Nagelkerke's R 2 , Harrell's C statistic, calibration-in-the-large, calibration slope and decision curve analysis. Internal–external cross validation was used to evaluate model performance across nine geographic regions. A risk score was derived from the original coefficients. Results A total of 338 981 patients were included. The overall 1-year cumulative incidence rate of MACE following COPD exacerbation was 5.04% (95% confidence interval 4.96–5.12%). Six predictors were retained: age, exacerbation severity, MACE history, modified Medical Research Council dyspnoea scale, hypertension and diabetes. In internal–external cross validation, the pooled estimation for Nagelkerke's R 2 was 3.120% (2.945–3.295%) and Harrell's C statistic was 0.752 (0.746–0.759). Calibration-in-the-large was −0.006 (−0.008– −0.004) and the calibration slope was equal to 0.999 (0.977–1.020). These results suggest that the model has clinical utility, with higher net benefit than default strategies across the risk thresholds range from 2% to 18%. Model-driven risk stratification demonstrated significantly different cumulative incidence rates among these risk categories. Sensitivity analysis revealed that the CE-MACE model is generalisable to those patients with any history of COPD exacerbation. Conclusion The CE-MACE model highlights the burden of cardiovascular multimorbidity in patients with COPD. The model could help precisely identify those at high risk in clinical practice and promote integrated multidisciplinary healthcare for these patients.