External validity of a contemporaneous primary percutaneous coronary intervention trial in patients with acute ST-elevation myocardial infarction: insights from a single-centre investigation

Abstract

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. KEYWORDS• clinical research • clinical trial • death • drug-eluting stent • STEMI

Rehospitalizations Following Primary Percutaneous Coronary Intervention in Patients With ST‐Elevation Myocardial Infarction: Results From a Multi‐Center Randomized Trial

“…First, although COMFORTABLE AMI was designed as an all‐comers STEMI trial, ≈40% of patients presenting for STEMI were not included in the trial, leading to an underestimation of RH frequency, and the reasons and associated predictors of unplanned RH potentially differ. This is supported by a report that showed a higher rate of major adverse cardiovascular events in patients excluded from the COMFORTABLE AMI trial . Second, we did not record attendance to rehabilitation after primary PCI, a variable that is hypothetically attenuating the key end point of this study.…”

“…The main findings of this analysis on the frequency, reasons, and predictors of unplanned cardiac and noncardiac RHs post-PCI in patients presenting with STEMI can be summarized as follows: The largest evidence available on RHs after acute MI is derived from national data sets from the United States including more than 500 000 patients, in which one fifth were rehospitalized within 30 days. 8 Our lower rates of RH are explained by the selective inclusion of unplanned RHs only, as opposed to all-cause RHs, 8 the lower risk of RHs expected in a randomized, controlled trial with exclusion of very-high-risk patients (eg, baseline critical condition, high bleedings risk) 9 and the previously reported lower rates of readmission in European countries, when compared with the United States. 2 In the Assessment of Pexelizumab in Acute Myocardial Infarction trial, which enrolled over 5000 STEMI patients in 17 countries, the 30-day all-cause readmission was 11.3%.…”

“…This is supported by a report that showed a higher rate of major adverse cardiovascular events in patients excluded from the COMFORTABLE AMI trial. 9 Second, we did not record attendance to rehabilitation after primary PCI, a variable that is hypothetically attenuating the key end point of this study. Third, when multiple diagnoses coexisted in a hospitalization, we defined hierarchies that would allow categorization based on the cause of admission.…”