Mikhail Kosiborod, MD: DAPA-HF and DEFINE-HF Findings

On Monday morning at the Heart Failure Society of America (HFSA) 2019 Scientific Sessions in Philadelphia, PA, Mikhail Kosiborod, MD, presented new findings from the DEFINE-HF trial.

The trial, which observed the biomarker, symptomatic, and quality of life-related effects of SGLT-2 inhibitor dapagliflozin (Farxiga) in patients with patients with heart failure with reduced ejection fraction (HFrEF) regardless of diabetes status, rallied behind recent data from the DAPA-HF trial—which observed a similar patient population.

In an interview with MD Magazine® while at HFSA 2019, Kosiborod, a cardiologist and Director of Cardiometabolic Research at Saint Luke’s Mid America Heart Institute, detailed the significance of the DAPA-HF findings presented earlier this month—before touching on the new DEFINE-HF findings presented Monday.

On DAPA-HF findings from ESC 2019

Kosiborod: The DAPA-HF trial was just recently presented at the European Society of Cardiology, just about a week and a half ago. And the questions that were asked in the DAPA-HF trial—which was a really important, landmark study—was to try to understand whether SGLT-2 inhibitors, and specifically dapagliflozin, can be an effective treatment for patients with heart failure and reduced ejection fraction.

Now, what we already knew from cardiovascular outcomes trial and the SGLT-2 inhibitors on kidney outcome trials across different agents in the classes, is that it’s a very effective agent in preventing heart failure in high-risk patients with type 2 diabetes.

But what we didn't know is whether those agents that are effective in preventing heart failure can also be effective in treating patients that already have established heart failure specifically with reduced ejection fraction, and whether they are going to be effective in treating heart failure regardless of presence or absence of type 2 diabetes.

Remember: these were initially developed as type 2 diabetes medicines that lower blood glucose. The heart failure effects emerged in cardiovascular outcomes trials, but what wasn’t clear is will they be effective treatments for heart failure, and will they be effective as treatments for heart failure—regardless of diabetes.

And so what we saw the DAPA-HF trial is that the answer to both of those questions was a resounding yes. The compound dapagliflozin was highly effective in reducing death from

cardiovascular disease or hospitalizations for heart failure in that patient population of whom did not have type 2 diabetes.

On DEFINE-HF findings from HFSA 2019

And on top of that, it actually was highly effective in improving those outcomes regardless of type 2 diabetes status. It made no difference for the patients who did or didn’t have diabetes. The treatment effect was essentially identical.Kosiborod: The DEFINE-HF trial includes studies that we did in 26 centers in the United States, in a very similar patient population. These are patients both with and without diabetes, who have reduced ejection fraction heart failure.

And what we were looking at is the effects of the compound versus placebo on health status of patients with heart failure. What health status is, is symptom burden, functional status, and the quality of life in patients with heart failure.

So, remember that there are several key goals in managing heart failure. One is to reduce death and hospitalization rates. But the second and equally important goal of management is actually to improve the health status—to make patients feel better. So, to reduce symptom burden, improve functional status, and the quality of life—that's exactly what we're looking at in the DEFINE-HF trial.

That's a study where patients were randomized to dapagliflozin 10 mg daily or placebo, and followed for about 12 weeks. And what we observed, essentially, the main finding is that dapagliflozin was more effective than placebo in improving health status of patients with heart failure.

So a greater number of patients treated with dapagliflozin versus placebo had clinically meaningful and substantial, statistically significant improvements in their health status, as measured by the Kansas City Myopathy Questionnaire, which is kind of the gold standard of how you measure health status and heart failure.