Related Experiment Video
Updated: Aug 22, 2025
In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
Surgical or percutaneous coronary revascularization for heart failure: an in silico model using routinely collected
Suraj Pathak1, Florence Y Lai1, Joanne Miksza1
1Cardiovascular Research Centre, University of Leicester, Glenfield Hospital, Groby Road, Leicester, LE3 9QP, UK.
Insights
Coronary artery bypass grafting (CABG) may reduce 5-year mortality or cardiovascular hospitalizations compared to percutaneous coronary intervention (PCI) in heart failure patients. Further clinical trials are needed to confirm these findings for ischemic left ventricular dysfunction.
Area of Science:
- Cardiology
- Health Services Research
- Biostatistics
Background:
- High-quality evidence is lacking for choosing between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients with ischemic left ventricular dysfunction and heart failure (HF).
- In silico modeling using routinely collected healthcare data can emulate clinical trials to address evidence gaps.
Purpose of the Study:
- To compare the 5-year effectiveness of CABG versus complex PCI in patients with heart failure using an in silico trial design.
- To assess the association of CABG versus complex PCI with 5-year all-cause mortality or cardiovascular hospitalization.
Main Methods:
- An in silico trial was conducted using matched patient data from England's Hospital Episode Statistics and the STICH trial.
- Instrumental variable analysis (IVA) was employed, using regional variation in CABG versus complex PCI allocation as an instrument.
- The primary outcome was 5-year all-cause mortality or cardiovascular hospitalization.
Main Results:
- The emulated trial included 2046 heart failure patients who underwent CABG or complex PCI.
- Unadjusted rates for the primary outcome were 51.1% for CABG and 70.0% for PCI.
- Instrumental variable analysis indicated that CABG was associated with a significantly lower risk of the primary outcome (ATE 16.2%, 95% CI: -20.6% to -11.8%).
Conclusions:
- In silico modeling suggests that CABG offers a survival and hospitalization benefit over complex PCI in heart failure patients at 5 years.
- These findings highlight the need for a pragmatic clinical trial to definitively test this hypothesis.
- The feasibility of such a trial is supported by the in silico evidence.
Aims:
The choice of revascularization with coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI) in people with ischaemic left ventricular dysfunction is not guided by high-quality evidence.
Methods And Results:
A trial of CABG vs. PCI in people with heart failure (HF) was modelled in silico using routinely collected healthcare data. The in silico trial cohort was selected by matching the target trial cohort, identified from Hospital Episode Statistics in England, with individual patient data from the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Allocation to CABG vs. complex PCI demonstrated random variation across administrative regions in England and was a valid statistical instrument. The primary outcome was 5-year all-cause mortality or cardiovascular hospitalization. Instrumental variable analysis (IVA) was used for the primary analysis. Results were expressed as average treatment effects (ATEs) with 95 confidence intervals (CIs). The target population included 13 519 HF patients undergoing CABG or complex PCI between April 2009 and March 2015. After matching, the emulated trial cohort included 2046 patients. The unadjusted primary outcome rate was 51.1 in the CABG group and 70.0 in the PCI group. IVA of the emulated cohort showed that CABG was associated with a lower risk of the primary outcome (ATE 16.2, 95 CI 20.6 to 11.8), with comparable estimates in the unmatched target population (ATE 15.5, 95 CI 17.5 to 13.5).
Conclusion:
In people with HF, in silico modelling suggests that CABG is associated with fewer deaths or cardiovascular hospitalizations at 5 years vs. complex PCI. A pragmatic clinical trial is needed to test this hypothesis and this trial would be feasible.
