ACC: U.S. needs to get with the program for clinical trial participation
CHICAGO—A study looking to outline whether patients enrolled in clinical trials after acute MI found that two out of three MI patients were estimated to be eligible but did not participate in a clinical trial, according to a poster presentation March 26 at the 61st annual American College of Cardiology (ACC) scientific session. The researchers questioned whether clinical trial participants represent the broader U.S. MI population.

“This crystallizes the problem in a nutshell and that is that there is a general concern that the representativeness of our trial participants in our contemporary acute coronary syndrome heart attack trials are fairly under-represented because we have difficulty bringing in patients from the U.S.," Jacob A. Udell, MD, MPH, clinical fellow in cardiovascular medicine at Brigham and Women’s Hospital in Boston, told Cardiovascular Business.

U.S. patients have the poorest retention rates and are most difficult to keep in clinical trials. Therefore, it may be difficult to gain a true picture of cardiovascular trial results, Udell said.

During the study, Udell et al looked at patients who were enrolled in ACC’s ACTION Registry—Get With the Guidelines that includes information from 609 U.S. hospitals. The authors speculated that patients who were enrolled in MI clinical trials would have lower CV event rates, mortality and morbidity.

“We already know that patients involved in clinical trials do better,” Udell offered. “This is because we tend to cherrypick the best patients.”

Therefore, during this study, the researchers looked at the outcomes of patients who were enrolled in a clinical trial, those who may have been eligible and those who were not enrolled in a clinical trial. They evaluated captured data to assess whether patients were eligible to participate in clinical trials and whether they actually did.

Udell et al evaluated three ACS antiplatelet clinical trials: TRITON-TIMI38, PLATO and OASIS 7. They looked at inclusion and exclusion criteria to get a sense of “how many patients on paper looked like they would have been eligible to participate in clinical trials,” Udell said.  

Of the 289,322 patients who were enrolled in the ACTION registry between Jan. 1, 2007, and March 31, 2011, after exclusion, 141,135 patients were included in the analysis. Of those, 4,008 (3 percent) participated in clinical trials compared to 137,127 patients who did not participate in clinical trials. Of the patients who did not participate in clinical trials, 66 percent were eligible for, but did not participate, in a clinical trial and 31 percent were deemed ineligible for participation.

In terms of in-hospital outcomes, mortality was highest in patients who were ineligible to participate in trials compared to those who may have been eligible but did not participate and those who did participate, 8.4 percent, 2.5 percent and 1.5 percent respectively. These rates of major bleeds were 18.9 percent, 6.5 percent and 7.5 percent, respectively.

Patients who were either enrolled in a trial or eligible to enroll were reported to be younger, male, were less likely to have a prior cardiovascular history, received more evidence-based therapy, and received guideline-recommended care.

“Ineligible patients are an older and sicker group, and that we knew,” said Udell. “Patients enrolled in a trial are treated better either at admission, when undergoing a cath, in terms of length of stay or at discharge when compared to patients who on paper should have been eligible to participate in a clinical trial.”

But the reasons these patients who seemed eligible for trial participation but don't participate remain a mystery. “This is something we couldn’t capture,” Udell said. However, he speculated that it could be due to many factors including personality, those less likely to practice adherence or who may have a shorter life expectancy.

“This selection is really based on the gut instinct of the physicians,” Udell said.

Results showed that two out of three MI patients who were enrolled in the registry were eligible to be enrolled in a clinical trial. The researchers also adjusted for different variables such as prior MI, prior heart failure, and prior atrial fibrillation, among others.

Those ineligible for trial participation saw a two-fold increase in death post-MI.

“These results really underscore that there may be a generalizability concern about the results that we are seeing in routine clinical practice,” Udell said. “We need to all take a cautionary step into the future, and I say this as a member of a group doing many clinical trials. It underscores that we should always be careful about how we implement this, and appropriately implement this, only to patients who we truly study in our clinical trials.”

Udell said a limitation of the trial is the fact that the ACTION registry represents only 5 percent of U.S. hospitals.