DCRI study honored as practice-changing by New England Journal of Medicine

The ARISTOTLE study found that apixaban was superior to warfarin in preventing stroke and decreasing risk of bleeding for patients with atrial fibrillation.

A DCRI-led study published in 2011 was recently honored by the New England Journal of Medicine’s editor-in-chief as one of 12 studies that has most changed clinical practice since 2000.

The ARISTOTLE study found that apixaban was superior to warfarin in treating patients with atrial fibrillation who have an increased risk of stroke. Apixaban was not only more effective than warfarin in preventing stroke, but also caused less bleeding. The trial included more than 18,000 patients from 39 countries.

Prior to his upcoming retirement, Jeffrey Drazen, the editor-in-chief of the New England Journal of Medicine, looked back at the science the journal published over the 19 years he spent in the role. From more than 80,000 submissions and nearly 4,000 published studies, he selected 12 to highlight as “Drazen’s Dozen” of “practice-changing and lifesaving papers.”

“This is really quite an honor, as there are plenty of trials that are equally important,” said the DCRI’s Christopher Granger, MD (pictured), who served as a primary investigator and co-chair on ARISTOTLE. “This is a tribute to a great collaboration—both among so many people at the DCRI and worldwide, especially my co-chair Lars Wallentin from Uppsala University in Sweden.”

The DCRI team also credits its industry partners, Bristol-Myers Squibb and Pfizer, with contributing to the success of ARISTOTLE. The DCRI’s John Alexander, MD, MHS, who worked on ARISTOTLE, started studying apixaban with colleagues from Bristol-Myers Squibb in 2005, but the drug had an unfavorable risk-benefit profile in patients with acute coronary syndrome. By contrast, ARISTOTLE, according to Alexander, was “a home run.”

“It has been a rare privilege to be so intimately involved in the development of a drug that has made, and is making, such a difference in patients’ lives,” Alexander said. “I’ve been involved with a lot of trials, but none have had as great an impact on patient care as ARISTOTLE.”

Apixaban is now the most commonly initiated drug for stroke prevention for patients with atrial fibrillation, Granger said. It is easier to use than warfarin because warfarin is associated with several food and drug interactions and requires monitoring.

“It is gratifying to be able to generate evidence that can be used to help improve patients’ lives,” Granger said. “This honor aligns nicely with the DCRI’s mission to share knowledge that improves patient care around the world—we have been able to publish and share knowledge gained from ARISTOTLE that we now use every day in our practice.”

The DCRI’s Renato Lopes, MD, PhD, started working on the trial as a DCRI fellow, and later became part of the core leadership team of the study as a DCRI faculty member.

“When you work on a trial for so long and put in so much effort, it becomes part of your life,” Lopes said. “We are pleased that ARISTOTLE is still generating knowledge and helping patients all over the world, and it’s extremely rewarding and gratifying to be recognized for the work done by so many to make the trial successful.”

In addition to the primary manuscript published in 2011, there have been over 60 publications from ARISTOTLE with over half published in high-impact journals.

Other DCRI faculty who contributed to ARISTOTLE include Hussein Al-Khalidi, PhD, who was the statistician, and Sana Al-Khatib, MD, MHS, who ran clinical events classification for the trial. Many operational staff also contributed to ARISTOTLE’s success.