Gregg Fonarow, MD; David Aguilar, MD; Rob Mentz, MD; and James Januzzi, MD, discuss the unexpected and exciting use of SGLT-2 inhibitors to treat heart failure.
Gregg Fonarow, MD: Sodium-glucose cotransporter 2 inhibitors, that was mentioned as a way of preventing heart failure in patients with diabetes, may actually be a therapy for patients with heart failure even in the absence of diabetes. Some interesting speculation about mechanisms there, but large-scale trials are going on to evaluate a novel use of an already existing medication.
David Aguilar, MD: For now, the biggest excitement has to be with the SGLT2 inhibitors that are coming down [the pipeline]. There have been 2 studies which have both been positive for cardiovascular outcomes as well as heart failure. I think that the interesting thing about that is that the mechanisms behind why they're beneficial are kind of hard to explain. As we go back, taking the clinical results and try to explain it with science, we're learning that, perhaps, these medicines are working in ways that aren't specific to diabetes. What's happening now is that these medications, which started out as diabetic medications, are now being tested in people who have heart failure who don't have diabetes. It's taking these medicines, potentially, from being diabetic medicines and calling them cardiovascular medicines. I think that is interesting because there are new pathways and old pathways that we're revisiting that may provide further insight into cardiovascular disease and heart failure down the road.
Rob Mentz, MD: Probably the most exciting class is the SGLT2 inhibitor class because if you look at the development with EMPA-REG and then CANVAS, there were heart failure patients included in those [studies], but the focus wasn't on heart failure, regardless of diabetes. So now there are ongoing studies that are looking at the patients that have heart failure that may not even have diabetes, and looking at some of these agents that were obviously initially developed for diabetes. So you have large-outcome studies, but then also important mechanistic learnings from these studies that have been completed. Jim Januzzi [MD] and others, were involved in a nice paper that looked at trying to understand why we're actually seeing this cardiovascular benefit. What they presented is that you see canagliflozin actually having a favorable effect on the cardiac biomarkers.
James Januzzi, MD: The CANVAS program included CANVAS and CANVAS-R, which was the "second half" if you will, of the 2 trials, and the CANVAS program demonstrated a very similar reduction in cardiovascular risk (14% reduction, hazard ratio 0.86) for the triple major adverse cardiovascular event outcome of cardiovascular death, myocardial infarction, and stroke. That modest reduction in risk was accompanied by a rather robust 30% to 35% reduction in new-onset heart failure events, really arguing, very similarly, to what was seen in the EMPA-REG outcome study with empagliflozin, that these diabetes drugs really look like a heart failure therapy in disguise.