External validity of clinical trials in acute myocardial infarction

Arch Intern Med. 2007 Jan 8;167(1):68-73. doi: 10.1001/archinte.167.1.68.

Abstract

Background: Patients enrolled in randomized clinical trials (RCTs) may not reflect those seen in real-life practice. Our goal was to compare patients eligible for enrollment but not enrolled in contemporary RCTs of reperfusion therapy with patients who would have been ineligible and also with patients with acute myocardial infarction (AMI) participating in RCTs.

Methods: Consecutive patients with AMI (n = 8469) enrolled in the GRACE registry (Global Registry of Acute Coronary Events) were divided into 3 groups: RCT participants (11%; n = 953), eligible nonenrolled patients (55%; n = 4669), and ineligible patients (34%; n = 2847). Our main outcome measures were hospital mortality rates.

Results: Based on baseline characteristics or GRACE risk-score distribution, RCT participants had the lowest a priori risk of death; eligible patients had a higher risk; and ineligible patients had the highest risk. Actual hospital mortality showed a similar gradient (3.6%, 7.1%, and 11.4%, respectively) (P<.001). Multivariable analysis adjusting for baseline risk, use and type of reperfusion therapy, and delay from symptom onset to admission consistently showed a higher mortality rate for eligible nonenrolled patients than for RCT participants (odds ratio, 1.61; 95% confidence interval, 1.06-2.43; and odds ratio, 1.97; 95% confidence interval, 1.24-3.13, respectively).

Conclusions: Patients with AMI participating in RCTs have a lower baseline risk and experience lower mortality than nonenrolled patients, even when they are trial eligible. This difference is not entirely explained by differences in baseline risk, use and type of reperfusion therapy, and/or delays in presentation. Caution is necessary when extending the findings obtained in RCTs to the general population with AMI.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Female
  • Hospital Mortality / trends
  • Humans
  • Male
  • Middle Aged
  • Multicenter Studies as Topic / standards
  • Myocardial Infarction / mortality
  • Myocardial Infarction / therapy*
  • Odds Ratio
  • Randomized Controlled Trials as Topic / standards*
  • Treatment Outcome