4952Level A evidence - for A-level patients only? Participants in clinical trials post myocardial infarction have higher socioeconomic status and better prognosis
Authors: Svensson P , Ohm J , Johansson D , Discacciati A , Hambraeus K , Leosdottir M , Jernberg T 
Published: October 2019

Abstract

Introduction
Randomized clinical trials (RCT) produce the highest level of evidence and therefore form the basis for many guidelines. Their Achilles heel is external validity which is still poorly studied. Participants in clinical trials may partly be selected on unknown mechanisms in particular regarding socioeconomic status. To what extent participants in clinical trials after myocardial infarction (MI) are representative for the overall MI population is unknown.

Purpose
To investigate whether participants in clinical trials after myocardial infarction differ regarding socioeconomic status (SES), risk factor profile, prior and recurrent cardiovascular disease (CVD) events.

Methods
A total of 34,084 patients attending follow up after myocardial infarction between 2007 and 2014 were identified in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) out of which 3,037 had participated in a clinical trial. Information on disposable income, education level, marital status, prior CVD, risk factors and treatment were retrieved from national registers and patients were followed regarding recurrent CVD. Participants in clinical trials were compared to non-participants using logistic and Cox regression analyses. In a multivariable Cox-regression analysis adjustments were made for gender, age, inclusion-year, diabetes, LVEF, previous MI, previous stroke, prior cardiac surgery, ECG rhythm, eGFR, lipid levels, smoking status, use of ASA, use of ACE-I, use of beta-blockers, use of statins, level of education, disposable income and family status.

Results
Trial participants were more likely to be men (odds ratio (OR): 1.42; 95% CI: 1.29–1.55)), to be married (1.17; 1.09–1.27), to have a high income (1.58; 1.45–1.72), have a post-secondary education (>12 years) (1.33; 1.22–1.46) and less likely to be smokers (0.81; 0.72–0.90), have a reduced EF <30% (0.61; 0.46–0.80), history of previous stroke (0.79; 0.65–0.97) or MI (0.86; 0.77–0.97) compared to non-participants. The risk for recurrent CVD was lower among the participants compared to the non-participants (HR: 0.77; 95% CI: 0.67–0.88) and is illustrated in figure 1. In a fully adjusted model the lower risk remained after adjusting for age, gender, risk factors, prior disease including EF, evidence based treatments and SES (HR: 0.85; 95% CI: 0.74–0.97).
Trial participation and recurrent CVD

Conclusion
Participants in clinical trials after MI constitute a highly selected group with higher SES, a more favourable risk profile and a better overall prognosis. The lower risk after full adjustments imply that additional selection bias exists. The external validity of post MI- trials in general can thus be questioned. To what extent results from clinical trials apply to the overall post MI population should be carefully scrutinized. Real world registry data are important.

Acknowledgement/Funding
Familjen Janne Elgqvists Stiftelse