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Darren K. McGuire, MD, MHSc, at forefront of clinical trial evolution
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In this issue, Darren K. McGuire, MD, MHSc, professor of medicine in the division of cardiology, Dallas Heart Ball Chair for Research on Heart Disease in Women and Distinguished Teaching Professor at the University of Texas Southwestern Medical Center, Dallas, talks with Cardiology Today about cutting-edge research he’s been involved in, from PCSK9 inhibitors to diabetes medications to the medical implications of space exploration.
McGuire, who is also lead physician of the Parkland Hospital and Health System cardiology clinics in Dallas and a member of the Cardiology Today Editorial Board, received his medical degree from Johns Hopkins, completed his internship and residency at UT Southwestern and his cardiology fellowship at Duke University, and obtained an MHSc in clinical research from Duke in 2001.
McGuire has become an expert in large-scale clinical trial design and execution as well as drug registration and regulation, focusing on diabetes and CVD. He has held leadership roles in a variety of international CV outcomes trials, including in the areas of type 2 diabetes, obesity and lipids.
He formerly served on the FDA’s Cardiovascular and Renal Drugs Advisory Committee and is currently an FDA ad hoc consultant. He also serves as a deputy editor of Circulation and senior editor of Diabetes and Vascular Disease Research. Previously, he was associate editor of the American Heart Journal, associate editor of Obesity and co-editor of the textbook Diabetes in Cardiovascular Disease: A Companion to Braunwald’s Heart Disease. He has written or co-written more than 240 peer-reviewed manuscripts, reviews, editorials and book chapters and won several outstanding teacher awards.
Who has had the greatest influence on your career?
Dr. McGuire: The first is Daniel W. Foster, MD, MACP, who was the chairman of medicine at UT Southwestern when I came here to begin my residency. He was very influential in my choice to come here. He’s a brilliant man, but he also has remarkable humanism and demanded that we take care of our patients at Parkland Hospital — the indigent-care or safety-net hospital — with the same care and dignity as we would our own family members. He instilled in all of us, and still does, a great level of compassion and respect and honor for our profession. He considers being a physician the greatest honor in his life and encourages us to pass the legacy of professionalism of our career.
Another is Robert M. Califf, MD, MACC. I went to Duke specifically with the intent to train with him and the group he led there executing international clinical trials. I saw him as a mentor; he remains a mentor, as do many who were with him at the time, including Robert A. Harrington, MD, FACC, FAHA, FESC, and Eric D. Peterson, MD. I met a lot of influential people at Duke Clinical Research Institute who I continue to collaborate with on international clinical trials.
Image: Marty Perlman
Here at UT Southwestern, I am continually influenced and pulled toward excellence by my colleague James A. de Lemos, MD; my lifetime mentor Jere H. Mitchell, MD; and our division chief, Joseph A. Hill, MD, PhD.
What area(s) of research in cardiology interest you the most right now?
Dr. McGuire: Large-scale international clinical trials. It’s what I trained to do and what I’m actively participating in. I think the most exciting part of what we’re doing is creatively building new models to execute the trials we’re conducting, capitalizing on technology and developments and databases, and trying to execute the trials with increasing quality and efficiency. A lot of people are creatively tapping registries of patients to perform randomized trials within registries. We’re looking toward that for some trials we are developing now. We are also using the electronic health record as an efficient data-capture and data-abstraction source to monitor patient outcomes in clinical trials.
What advice would you offer a student in medical school?
Dr. McGuire: The same advice that was given to me long ago, which I think remains the most important: As you go through your training, follow your passion. Don’t try to be something you think you should be or others think you should be. Know that the work that we do is hard and grueling, and if it’s not a passion, it can be a fairly difficult career. If you can identify and singularly follow a specific passion, which I’ve done with diabetes, it is very rewarding. So, as a cardiologist, I became interested in diabetes as a CV disease and it has been extremely rewarding sticking on that path for more than 20 years.
Have you ever been fortunate enough to witness, or to have been a part of, medical history in the making?
Dr. McGuire: Yes, I have. I’ll give two examples. No. 1, I’m an investigator with the Dallas Heart Study. From this study, a discovery of the PCSK9 mutation was made by others in our group that ultimately led to most drug companies around the world with a lipid program immediately refocusing on efforts to develop PCSK9 inhibitors. I had the great fortune of being able to sit in a room with Helen H. Hobbs, MD, and Jonathan Cohen, PhD, who made the discoveries in our database, to pore over the data and work with them to try to figure out what this means and how it might be important clinically. I tell everybody the result was my proudest publication and I’m not a co-author. In The New England Journal of Medicine article in 2006 about that discovery, at the very end I’m acknowledged in small italics as having contributed to the development of the manuscript. While I am not a co-author, I’m very proud to have been acknowledged in there with two Nobel laureates, Michael S. Brown, MD, and Joseph L. Goldstein, MD, along with Scott M. Grundy, MD, PhD, who was chairman of the Adult Treatment Panel of the National Cholesterol Education Program, and my close partner James de Lemos.
No. 2, I did a year of physiology research in between residency and fellowship. During that year, I got to go with my mentor, Jere Mitchell, to an advisory panel in Bethesda, Maryland, where NASA’s Space Life Sciences Program and the National Institute on Aging had convened some experts. Sen. John Glenn came into the room and we spent a day and a half talking about the medical interests of a 70-year-old orbiting. We ended up developing white papers that were used to support Sen. Glenn’s re-orbit at the age of 70.
What was the defining moment that led you to your field?
Dr. McGuire: When I was a resident, I picked a topic for a conference called Ischemic Preconditioning. When I picked the topic, I knew nothing about it and I thought it had to do with collateral blood vessels forming in the heart. I quickly realized as I began to prepare the talk that the entire paradigm of ischemic preconditioning had nothing to do with blood vessels, but instead was a complex biologic pathway hinging on the effects of a specific potassium channel. That potassium channel is the target of action of one of the most commonly used classes of diabetes medicines, the sulfonylureas. As I got into the field, I realized we had really no evidence whatsoever not only about the efficacy but even the safety of the medications we were using for type 2 diabetes from a CV perspective. I saw that as a real unmet clinical need and decided to follow that path as a career. So I went to Duke and got formal training in the conduct of international clinical trials, biostatistics and epidemiology, and that’s been my career ever since. It was a completely serendipitous choice of a topic for a conference when I was a second-year medical resident. – by Erik Swain