Dr Milton Packer Discusses the Combined Impact of EMPEROR-Reduced, DAPA-HF

It's very important to take the EMPEROR-Reduced and DAPA-HF trials together as being complementary, said Milton Packer, MD, a distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas, and chair of the department of clinical sciences at the University of Texas Southwestern Medical School.

The American Journal of Managed Care® (AJMC®): A major difference in the EMPEROR-Reduced study compared with DAPA-HF is the fact that the study population in EMPEROR-Reduced had more advanced heart failure. What will this mean in clinical practice?

Dr. Packer:I think that it's very important to take the EMPEROR-Reduced and DAPA-HF trials together as being complimentary trials, which studied a broad spectrum of patients with heart failure and a reduced ejection fraction, with and without diabetes. A way of thinking about it is these are sister trials. They weren't identical. They studied somewhat different populations, but they produced exceptionally concordant results. It is much more informative not to look at each trial in isolation, because they studied a specific population in a specific way, but to look at the 2 trials together, look at the totality of the available evidence, especially since the benefits of the drugs in the 2 trials were so similar.

AJMC®:You discussed the ability for patients with heart failure to benefit from SGLT 2 inhibitors depends on the willingness of cardiologists to prescribe them. In your view, what have been the barriers to cardiologists embracing this drug class to treat heart failure, given the evidence?

Dr. Packer:It is not just cardiologists who have been slow in prescribing drugs that are effective for the treatment of heart failure. It's all physicians. Remember that most patients with heart failure and are not taken care of by cardiologist. Around 80-85% are taken care of by primary care physicians. It is true that cardiologists prescribe newer drugs faster than primary care physicians, but many cardiologists are also slow in prescribing these drugs. It's very unfortunate because now we have 4 drugs, which have a meaningful effect and can modify the course of the disease. These are disease modifying drugs. That means that all patients with heart failure with a reduced ejection fraction should be receiving all 4 drugs: angiotensin receptor neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists, and now SGLT 2 inhibitors. And they should be receiving them at the doses that have been shown to reduce morbidity and mortality. But fewer than 1% of patients with heart failure in the United States are receiving all these drugs at target doses. So, there is a substantial under prescribing of these drugs. The reasons are complex. Some of it is that it is often perceived by physicians that while the patient is stable, that they don't have to intensify therapy. But in fact, the trials show that it is the stable patient, whose symptoms have remained essentially unchanged, that benefits dramatically from these drugs. Some physicians may worry about the forms that need to be filled out. The obstacles that payers place in allowing physicians to prescribe these drugs. But this is an unfortunate consequence of the way our health care system is and physicians really owe an enormous responsibility to patients with heart failure to make sure they're treated properly.

AJMC®: Will having results from EMPEROR- Reduced a year after DAPA-HF increase cardiologist's comfort with SGLT 2 inhibitors?

Dr. Packer:I think the 2 trials, EMPEROR Reduced, DAPA-HF, put together provides such strong reinforcing evidence. I think the 2 trials together are far more compelling than either trial alone. And the striking concordance of the effect on hospitalizations, the effect on quality of life, functional class, these are benefits that have not occurred by chance alone. This is a direct effect of these drugs. And now it's been seen in 2 trials.

AJMC®:How important is the fact that empagliflozin was the original SGLT 2 inhibitor to show the benefit of CV outcomes and, specifically, reducing hospitalization for heart failure?

Dr. Packer: Well, we now have trials with many different SGLT 2 inhibitors. Empagliflozin may have been the first. We now have data with dapagliflozin, canagliflozin, ertugliflozin across a number of very well done large-scale trials in patients with type 2 diabetes, in patients now with chronic heart failure, in patients with chronic kidney disease. The concordance of the data across multiple members of the same class, across multiple disease states is really impressive.