COMMENTARY

ESC 2019: Which Trials Could Change Cardiology Practice?

Mamas A. Mamas, BM, BCh, MA, DPhil, FRCP.

Disclosures

September 03, 2019

Hi, welcome to Medscape UK. My name is Mamas Mamas, I'm professor of cardiology from Keele University in the United Kingdom and I'm going to talk about the highlights of the European Society of Cardiology held in Paris 2019.

This year has been a huge meeting. It has been a meeting where real practice-changing trials have been presented. It's been a meeting that has been an explosion of social media. The ESC have appointed over 50 social media ambassadors from all over the globe. There's been millions of tweets and impressions around all the exciting science of the ESC.

So what are the trials that have really stood out in my view?

Well, I think there've been a number.

COMPLETE Trial

There's been trials like the COMPLETE trial, (Complete vs Culprit-Only Revascularization Strategies to Treat Multi-vessel Disease after Early PCI for STEMI), a randomised control trial of over 4000 patients, presenting with STEMI with multi-vessel disease. And it was a randomisation between those that had complete revascularisation, either as in-patients or up to 45 days, versus target lesion only revascularisation.

There have been a number of trials in this arena in the past, and most of them have been very small and really underpowered to detect hard clinical end points. The COMPLETE trial is the largest today by several orders of magnitude with over 4000 patients.

What this study showed was the composite end point of cardiovascular death and MI was reduced by over 25% in the complete revascularisation arm.

The other interesting thing about this trial was that it didn't appear to matter whether the complete revascularisation was achieved in the in-hospital setting, or following discharge up to 45 days. So I think it's the completeness of revascularisation that matters rather than the timing of revascularisation that matters.

Will it change practice? I think so. I think it will very much change practice. I think there are some questions around for example, whether the anatomical site is important. So for example, there did seem to be a significant P for interaction for proximal LAD, mid LAD, compared to other territories. And that would make sense in terms of the areas subtended.

ISAR-REACT 5 Trial

Other trials that I think are really going to change practice are the ISAR-REACT 5 trial.

We know that randomised trials comparing prasugrel versus clopidogrel, and ticagrelor versus clopidogrel, have shown superiority but there hasn't really been an adequately powered head-to-head trial.

There was one, the PRAGUE trial, which was discontinued because of poor recruiting and secondly, because of the low event rates.

So what did the ISAR-REACT trial show? This was a trial of over 4000 ACS patients randomised to receive either prasugrel or ticagrelor. And they showed that the composite endpoint of death, MI, or stroke was associated with a 30% increase in the ticagrelor arm.

This is interesting for several reasons. First and foremost, you are comparing a pre-treatment algorithm with ticagrelor versus a treatment algorithm after the angiogram following prasugrel.

So this is really telling us that perhaps we don't need to treat patients, or pre-treat patients, before the cath and treating them at the time of the angiogram when a decision for PCI is made, might be the right thing to do.

There was no differences in bleeding outcomes. And certainly, I think this will provide important guidance in the space, as interventional cardiologists, looking around the UK, there's very different practice. We published an observational study using BCIS (British Cardiovascular Interventional Society data) 2 years ago, comparing prasugrel and ticagrelor. And again, prasugrel had better outcomes.

But looking at practices of usage, very different in different regions of the country. I think this trial, ISAR-REACT 5, will really give us guidance about optimising antiplatelet therapy in this population of patients.

THEMIS Trial

The other trial that I think was quite interesting, sticking with coronary syndrome, is the THEMIS trial.

This is a large trial of over 11,000 patients undertaken in diabetics. This was in patients with known coronary artery disease, without previous history of MI or stroke. And the primary outcome was cardiovascular death, MI, or stroke.

And this showed that ticagrelor compared to placebo was associated with a 10% reduction in the primary endpoint. Although this was offset by over two and a half increase in TIMI major bleeding.

And again, what we're seeing here, as we've seen in many of these studies is a balancing act. A balance between reducing ischaemic events versus increasing bleeding events. Whether there's any role for trying to identify the high ischaemic low bleeding, you know, that's a nice concept. The problem with the nice concepts is that they often don't work in clinical practice. Often patients with a high ischaemic burden are often those with a high bleeding burden.

DAPA-HF Trial

Moving on to heart failure, the two big heart failure trials, number one being the DAPA-HF trial.

This is with over 4744 patients with an SGLT2 inhibitor, randomised. And this showed a 26% reduction in heart failure events or cardiovascular deaths.

SGLT2 inhibitors have been shown to decrease incident heart failure in the past, but this is one of the very first and largest trials looking at dapagliflozin and showing that dapagliflozin in both diabetics and non-diabetic individuals can reduce the composite endpoints. It can reduce cardiovascular death individually and heart failure-related events, such as heart failure hospitalisations, or increasing therapy because of worsening heart failure.

How will this change practice? I think this will really change practice hugely. One of the discussions is who should be starting dapagliflozin? Should it be diabetitians? Should it be cardiologists? Should it be the general medics?

This was truly huge differences in the primary outcomes, and secondary individual outcomes, irrespective of diabetic subtype. And also this was a well-managed cohort. I think this is going to have a major impact in how we treat our heart failure patients.

PARAGON-HF Trial

The final trial is the PARAGON-HF trial, using sacubitril/valsartan (Entresto, Novartis) in patients with preserved ejection fraction (HFpEF), and the primary outcome was heart failure hospitalisation or cardiovascular death, and there was no significant impact on outcomes associated with Entresto.

There did seem to be a signal that there was perhaps a significant effect in women in the secondary analysis, in secondary subgroup analyses there was a benefit in patients with an ejection fraction of less than 57%. So I think this should be purely hypothesis generating, it certainly won't impact on my practice, on how I treat these patients.

I think really, what it shows is that HFpEF has a poor prognosis, and we really don't have that many effective treatments.

Best ESC Meetings to Date?

So thank you for joining me. I think this has been one of the best ESC meetings to date. I've been very impressed by how global it is, the quality of the science, the quality of social media coverage, and the organisation. So congratulations to the organisers. And please let me know what you think are your favourite trials. Thank you.

You can follow Mamas Mamas on Twitter

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