COMMENTARY

ESC: DAPA-HF & SGLT2 Inhibitors a Year on

Prof John McMurray

Disclosures

September 01, 2020

Prof John McMurray, University of Glasgow, on SGLT2 inhibitors in UK clinical practice.

This transcript has been edited for clarity.

Hello, I'm John McMurray from the University of Glasgow in Scotland.

What are the headlines a year on from DAPA-HF? [1]

In the past 12 months, we've had the opportunity to delve much more into the DAPA-HF [2] database.

I would say some of the highlights of what we find are, firstly, the demonstration that dapagliflozin is very effective in heart failure patients without type 2 diabetes, so getting away from the idea that this is just a glucose-lowering drug.

We've also looked more at quality of life and symptoms, again, demonstrating probably bigger benefits in symptoms and quality of life than we've seen with any previous drug.

And then another publication that I particularly like from these analyses was looking at age, because we included patients in DAPA-HF who were over the age of 90. We had a substantial number of older individuals, and they're more typical of the people that we see in the UK.

And in fact, again, we found an entirely consistent benefit right across the spectrum of age. And remarkably, dapagliflozin was also extremely well-tolerated in even quite elderly individuals, and for some adverse effects, they were less frequent in the dapagliflozin group than the placebo group, and that particularly relates to renal dysfunction. Although, of course, we now know that these drugs clearly do prevent the progressive worsening of renal function over time. So those are some of the things that we've looked into, many more as well. But those are my highlights I suppose.

To what extent does EMPEROR-Reduced complement your findings?

I think EMPEROR-Reduced[3] is very important for a number of reasons.

Firstly, they enrolled a slightly sicker group of patients in that trial. So the event rate was higher in EMPEROR-Reduced. So I think we now know more about the effect of SGLT2 inhibitors across the spectrum of severity of heart failure.

Secondly, their results were, by and large, very consistent with ours.

So if we take the composites of time to first occurrence of heart failure hospitalisation, or cardiovascular death, the treatment effect sizes were absolutely identical. I've never seen anything quite so similar.

There were some other differences. They didn't see a reduction in mortality. I'm not sure why, whether it was bad luck or something else we did. On the other hand, they found a reduction in a renal composite outcome. We didn't. Our effect on that composite was not statistically significant.

But I think maybe the most important finding in EMPEROR-Reduced was that the benefit of empagliflozin in that trial was entirely consistent in the large subgroup of patients they had who were treated with sacubitril/valsartan on top of all the other standard medications that we would use in patients with heart failure reduced ejection fraction.

Sacubitril/valsartan was our last big breakthrough in heart failure. Everybody wants to know, should we be using one or other, or both of these drugs?

They have clearly demonstrated that when you add an SGLT2 inhibitor to sacubitril/valsartan you get exactly the same benefit as you see in patients who are not on sacubitril/valsartan. In other words, the treatments are complementary. Their benefit is additive. We’ve seen the same in DAPA-HF but it was very important to have this confirmed, especially since in the EMPEROR-Reduced trial there were more patients on sacubitril/valsartan at baseline.

In UK clinical practice, how are you finding the crossover between cardiologists, diabetologists, and general practice for SGLT2 inhibitors?

The interesting thing is that patients with heart failure and diabetes are seen more by cardiologists, and by general practitioners than they are by diabetologists, usually. So cardiologists have to learn that this is now our drug. This is a drug that's been repurposed. SGLT2 inhibitors were originally introduced as glucose-lowering drugs, and of course they are that, and they are treatment for type two diabetes, but they're also specifically a treatment for heart failure.

The example I use is sildenafil that was introduced as a treatment for erectile dysfunction is now widely used as a treatment for pulmonary hypertension. Completely different indication, same molecule, but doing different things. And there are other examples of that.

So we have repurposed this drug for heart failure. Now the good news is because SGLT2 inhibitors are out there, because general practitioners are used to using them, because they've used them in type 2 diabetes already, I don't really foresee any problem in this treatment becoming widely used, because it deserves to be, because of the enormous benefits that we've seen.

You've been presented with the ESC Gold Medal. What does that mean to you?

It means a tremendous amount because it's an enormous honour. I feel very humbled, given all the other amazing people who have been awarded this in the past.

It's the highest recognition I can get from my peers and my speciality in Europe.

But I'm delighted to accept it on behalf of all my colleagues. I am a figurehead for many, many people who do all the work, my researchers in clinical trials, of course. While I might get to lead them and stand up on the stage, there are many, many, many more people involved in doing that.

I've got great friends, colleagues, mentors around the world, and really, it's my pleasure to accept this award on their behalf.

How have you found the virtual conference compared with face-to-face networking?

I miss the networking, I really do miss that. On the other hand, it's so easy to sit and watch the things that you want to see.

I've probably seen much more of this Congress than I would have if I was actually physically there because there would be a lot of networking. Whereas here I can sit and watch things that really interest me if I missed them live and can go and look at them again.

The viewing figures have been phenomenal.

I have to say, I suspect going forwards, we're going to have to do a blend of this because I think it's been tremendously successful.

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