In the September 23rd issue of JACC, George Dangas, MD, and colleagues took a look at the long-term outcomes of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in insulin- and non–insulin-treated diabetic patients in the FREEDOM trial. In an accompanying editorial comment, Steven P. Marso, MD, looked at whether the final chapter on this particular issue has finally been written thanks to FREEDOM. Dr. Marso is a professor of medicine and medical director of interventional cardiology at University of Texas Southwestern Medical Center. This interview was conducted at TCT 2014 in Washington, DC.

CSWN: Tell us about the FREEDOM trial, because this is a fascinating story that has been around for a while. Refresh our memories.

Steven P. Marso, MD: It is. We've been interested in diabetes and cardiovascular disease my entire career for 15 years and the FREEDOM trial is an incredibly pivotal, landmark trial looking at angioplasty and PCI techniques versus CABG in patients with diabetes mellitus. It's an incredibly informative trial, to be sure.

What were the results that they first came up with? This is not the first time we've heard from FREEDOM.

That's exactly right. The investigators published it now a couple of years ago, and the FREEDOM trial demonstrated in 1,900 patients that bypass surgery was superior to PCI techniques in people with diabetes and multivessel disease. The benefit was really impressive if you look at the primary composite endpoint of all-cause mortality. There was also a significant reduction in myocardial infarction (MI). My bias is that one of the things that drives the adverse events in people with diabetes is nonfatal MI risk. It's two to four times higher than anybody in the population. It's true that we've driven down the MI rates with statin therapy and aspirin therapy, but people with diabetes still have a really high proclivity to experience a nonfatal MI. Bypass surgery is better than angioplasty in FREEDOM.

How will new data that have been published in JACC impact clinical practice?

Clinicians have to generalize the results of FREEDOM to their practice, and one of the ways you do it is to try to figure out subgroups of interest. In general, you should generalize the results from FREEDOM to everybody, but it's hard to do that in clinical medicine. FREEDOM was a subpopulation of who we treat. Clinicians look at things they understand, with insulin treatment being one of them, and complexity of disease like the SYNTAX score being another. The article by Dr. Dangas helps to describe the treatment benefit in patients with diabetes who are managed with insulin. Historically, insulin is a marker of risk, and Dangas et al. showed that—if you're treated with insulin, the risk goes up, and that's true in the FREEDOM sub-study.

The SYNTAX trial demonstrated the treatment effect in insulin-treated patients, randomizing people to bypass surgery and stent techniques. The SYNTAX results showed us that if your patients were treated with insulin, the treatment effect with CABG was higher than in orally-treated patients. In fact, PCI in that subpopulation was actually better numerically than bypass surgery. One could extrapolate that Dangas et al. would have expected the treatment effect of bypass surgery should be higher in insulin-treated patients versus non–insulin-treated patients. It wasn't true. The treatment effect was numerically lower than orally-treated patients. Does that diminish the effects of FREEDOM? Absolutely not. It's a substudy. They're directionally similar, but the magnitude of benefit, in my opinion, is lower than what would have been expected from, say, SYNTAX or other clinical trials.

Does this help solve the debate that people have been having for a few years?

Well, I think it's another line of evidence in line with the original BARI trial and the SYNTAX substudy of people with diabetes. FREEDOM is the largest, most definitive clinical trial, so I think the evidence and the guidelines will change based upon this trial. The guidelines will suggest, in my opinion, that CABG is preferred over PCI in people with diabetes and multivessel disease. As a clinician and a researcher who is vested in this space of diabetes, I have to say it doesn't answer all the questions. With many trials, other questions are raised. For example, the benefit in a lower-risk person with diabetes, or someone with one- or two-vessel disease with a SYNTAX score less than 22 where the treatment effect is less than with higher disease. Those are unanswered questions. We'll have to figure that out over time. FREEDOM was a pivotal trial. It was informative, and I think clinicians should use this information daily in their practice.

Marso S, McGuire D. J Am Coll Cardiol. 2014;64:1198-201.

Keywords: Washington, Insulin, Myocardial Infarction, Physician Executives, Aspirin, Coronary Artery Bypass, Angioplasty, Diabetes Mellitus, Stents, Percutaneous Coronary Intervention

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