Aims: Randomised controlled trials (RCTs) represent the most robust source of evidence-based medicine. However, the generalisability of RCTs is limited by the inclusion of selected populations. We sought to assess the external validity of a contemporary trial including patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).
Methods and results: Patients presenting to Bern University Hospital during the inclusion period of the COMFORTABLE AMI trial were divided into three groups: RCT participants (41%), eligible not included (17.5%), and excluded patients (41.5%). Major adverse cardiac events (MACE) were defined as one-year death and myocardial infarction. RCT participants compared with RCT-eligible patients had comparable baseline characteristics and outcomes; however, excluded patients differed in risk and had higher rates of MACE (HR 3.63, 95% CI: 2.03-6.48, p<0.001), death (HR 6.23, 95% CI: 2.93-13.24, p<0,001) and definite/probable stent thrombosis (HR 3.63, 95% CI: 1.79-7.36, p<0.001). Inability to provide consent was the most frequent exclusion criterion and was independently associated with an increased risk for MACE (HR 6.85, 95% CI: 3.97-11.81, p<0.001).
Conclusions: In this single-centre investigation, results from the COMFORTABLE AMI trial appeared applicable to a broad representation of RCT-eligible patients. However, patients excluded from the trial represented a higher-risk population with impaired clinical outcomes and a lower adherence to cardiovascular medication.