ESC 2019: Antiplatelets in Diabetes, CAD and A-fib, an ARNI in HFpEF, Staged Complete PCI, and More

For only the second time in recent memory, the European Society of Cardiology (ESC) Congress 2019 is heading back to the City of Light with a program that promises to illuminate several key issues in cardiovascular medicine. The meeting kicks off in Paris on Saturday, August 31, and runs through Wednesday, September 4.

“I think that the Hot Line sessions, and the program in general, is really very diverse and in all its facets, I believe, is very high quality,” ESC President Barbara Casadei, MD, DPhil (University of Oxford, England), told TCTMD. “So whether you are interested in the latest clinical trials, in policy, in alternative clinical trials—such as how do you manage and implement research, rather than this drug versus this drug—or in how to have a more global approach to diseases and patients, or whether you are interested in basic science, or in innovation, I think there is something for everyone. That’s a bit of a hackneyed phrase, but in this case, I really believe it's true.”

And, as it has happened at least twice in the past (in 1994 and 2006), ESC has partnered this year with the World Heart Federation such that the World Cardiology Congress (WCC), held last year in Dubai, will be jointly held with ESC 2019. Moreover, the official meeting “spotlight” is global cardiovascular health.

I think there is something for everyone. That’s a bit of a hackneyed phrase, but in this case, I really believe it's true. Barbara Casadei

“More than three-quarters of cardiovascular deaths today occur in low- and middle-income countries,” said Marco Roffi, MD (University Hospital of Geneva, Switzerland), who along with Silvia Priori, MD, PhD (IRCCS Fondazione Salvatore Maugeri, Pavia, Italy), is a program chair for this year’s congress. “We are very much interested to see what are the options and how we can ease and get help for this taxing burden beyond European borders.”

Hot Line Trials

ESC Congress “Hot Line” trials this year are grouped across six sessions, two per day on Sunday, Monday, and Tuesday. Roffi, who walked TCTMD through some of the big-name studies in the lineup said that organizers are “very happy” with the breadth of cardiology topics among the trials submitted, as well as the wide-ranging geographies represented among those selected. “We will have trials on antithrombotic treatment, trials on heart failure, trials on ACS, both on the diagnostic side and on the treatment side,” Roffi said. Many, he added, are sizeable, “eagerly awaited” studies.

THEMIS, for example, is a trial of more than 19,000 patients with diabetes and preexisting coronary disease or prior PCI, testing twice-daily low-dose ticagrelor versus placebo for the prevention of CV death, MI, or stroke. A second prespecified analysis from this trial, THEMIS PCI, is looking exclusively at the prior-PCI subset, representing more than 10,000 patients—both are part of Hot Line 1, Sunday morning.

Also part of this first session is PARAGON-HF, comparing sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), to valsartan alone in patients with NYHA class II-IV heart failure with preserved ejection faction. “HF with preserved ejection fraction is an epidemic because of aging and other reasons, and it’s very frustrating, from a therapeutic standpoint, because we have very little in terms of drugs for prognosis improvement and symptom relief, so there is a huge need,” Roffi said.

Next up in Hot Line 1—and highlighted by Roffi—is COMPLETE, looking at culprit vessel revascularization in STEMI versus staged complete revascularization. This is a “strategy” trial enrolling more than 4,000 patients, making it substantially larger than prior studies in this space, explained Roffi. The study aims to establish whether a “staged” approach to complete revascularization can work in stable, STEMI patients without cardiogenic shock. European guidelines have already been updated to recommend complete revascularization over culprit-lesion only, but the timing of treatment for the nonculprit lesions has not been established. This is “the most clinically relevant question,” Roffi said, for operators on call for STEMI patients. “No one, at 2 AM, wants to go after the nonculprit lesion.”

Rounding out this first Hot Line is the last-minute addition of DAPA-HF, looking at dapagliflozin to prevent adverse outcomes in heart failure patients, both with and without diabetes. Topline results, released earlier this week, indicate that the trial met its primary endpoint, but full details await Sunday’s presentation.

These first five trials kicking off the Hot Line 1 represent a “strong start,” Roffi acknowledged, noting this was by intent. But he stressed that a handful of other trials distributed across the rest of the Hot Line sessions should also generate discussion and potentially lead to changes in practice.

Hot Line 2, Sunday afternoon, emphasizes ACS trials, said Roffi, pointing to a few standouts.

• NZOTACS is a 38,000-patient trial from New Zealand looking at supplemental oxygen in the setting of acute coronary syndromes. This comes on the heels of DETO2X-AMI, the unexpected blockbuster from ESC 2017 that showed no benefit of supplemental oxygen in the setting of suspected STEMI. NZOTACS, focused on suspected ACS patients and examining two different oxygen protocols based on saturation levels, used countrywide data over a 2-year period and has an endpoint of 30-day total mortality.
• ISAR-REACT 5 is a randomized, open-label, head-to-head comparison of ticagrelor versus prasugrel in patients with ACS, the first such comparison, Roffi said. The 4,000-patient, multicenter trial (conducted in Italy and Germany) will also help clarify whether patients benefit from pretreatment with ticagrelor, something that has not been specifically studied in a randomized trial of ACS patients, Roffi noted. Pretreatment is not advised for prasugrel, following the results of the ACCOAST trial. ATLANTIC, which looked at ticagrelor pretreatment in STEMI patients, did not meet its primary endpoint.
• Roffi also highlighted two studies on the ACS “diagnostic side,” one of which is part of Hot Line 2. HiSTORIC is a step-wedge, cluster, randomized trial of high-sensitivity cardiac troponin I as a rule-out test in patients presenting with suspected myocardial infarction. At 39,000 patients, said Roffi, HiSTORIC, from Scotland, is “a huge trial” that should “really give us some insights.” A second trial, to be presented during Hot Line 6, also focuses on the newer tests: the Australian RAPID TnT study, with an intended enrollment of 5,400, is randomizing suspected ACS patients to a 0/1-hour rule-out algorithm using high-sensitivity cardiac troponin T or to the standard troponin testing at 3 and 6 hours. The trial hopes to demonstrate the superiority of the faster, more sensitive test with an endpoint of all-cause death or recurrent ACS at 30 days.

Roffi stressed that all of the Hot Line sessions contain noteworthy trials—too many to cover on TCTMD—but highlighted two final studies, both of which are tackling the “important issue” of antiplatelet and anticoagulant drugs in patients with atrial fibrillation in coronary artery disease. The Japanese AFIRE trial, part of Hot Line 3, is looking at rivaroxaban (Xarelto; Bayer/Janssen) on top of antiplatelet therapy versus rivaroxaban alone in more than 2,000 patients with stable coronary disease and nonvalvular atrial fibrillation. “This will give us some nice safety and efficacy outcome information,” Roffi said.

The second study in this space is the 1,500-patient ENTRUST-AF PCI trial, to be presented during Hot Line 6. This time the study drug is edoxaban (Savaysa; Daiichi Sankyo), and it’s being compared with a vitamin K antagonist on top of a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) in patients with atrial fibrillation following successful PCI. Here, the endpoint is major or clinically relevant, nonmajor bleeding at 12 months.

Of special interest to interventional cardiologists will be Monday afternoon’s Hot Line 4, which includes 2-year results from MITRA-FR, the controversial MitraClip (Abbott) trial presented at ESC 2018 that famously delivered results at odds with COAPT, released 1 month later. Also in this session is 16-year follow-up from DANAMI-2 (primary PCI versus fibrinolysis in STEMI) and 10-year results from the SYNTAX Extended Survival trial, known as SYNTAXES (CABG versus PCI). SYNTAXES also made an appearance at TCT 2018.

Outside of the Hot Lines, there are 13 additional “late-breaking clinical science sessions” held Saturday through Tuesday, grouped by subspecialty.

New Guidelines

Beyond the late breakers, Roffi reminded TCTMD, the ESC always uses its annual congress to release new guidelines and updates. This year is no exception, with a total of five new guidelines being unveiled on the opening day of the meeting and discussed in sessions throughout the program. These are:

• Diabetes, Prediabetes, & Cardiovascular Diseases
• Acute Pulmonary Embolism
• Supraventricular Tachycardia
• Dyslipidemias
• Chronic Coronary Syndromes

This last, noted Roffi, represents the launch of new terminology for what was previously termed “stable coronary artery disease.”

Bells, Whistles, and a Global Focus

There are plenty of high-impact topics planned outside of the Hot Line and guideline sessions, both Roffi and Casadei noted. For example, the amount of programming on digital innovations has “doubled” in this year’s program and will be featured at “digital stages” dotted around the convention center. New this year are several “How Should I Treat” sessions spotlighting tough cases with expert input, as well as seven “live in a box” cases recorded at “internationally leading centers” and covering coronary, structural heart, alcohol septal ablation, and lead extraction procedures, followed by panel discussions.

Once again, the ESC has tried to reimagine the settings for these different types of programs, Roffi noted, with an emphasis on more openness and interactivity between speakers and their audiences.

In a nod to the “global spotlight” of this year’s meeting, other case-based sessions will showcase the kinds of problems being tackled not just in Europe but around the globe, while abstract submissions also reflect the international draw of this meeting. Fully 110 different countries submitted abstracts in 2019: Japan was the top-submitting country, followed by Russia, and for the first time the United States and Australia were among the top-five submitting nations, while China was in the top 10.

“This meeting is now so well regarded, we can increase the range of very good speakers from all over the world,” Casadei observed. And in fact, she stressed, the international flavor of this year’s meeting should be not only palpable but also instructive to all attendees, regardless of where they’re from.

“With the escalating costs of health, we really need to learn how to implement what we know in a more effective way, and drawing from the knowledge and experience of countries that have had to rationalize their expenses in health more than others can lend new solutions,” she said. “Sometimes having a tight budget makes you creative and helps in finding solutions that may then be applicable to other realities.”

While the digital programming is absolutely a highlight at this year’s congress, Casadei believes one message from the meeting should also be the need to innovate in terms of healthcare delivery. “We can get quite worked up about some niche details [for new drugs and devices], whereas all around the world there are really very much bigger issues in applying what we know in an effective way. This idea is reflected in the Hot Lines as well as the registry sessions, where we have quite a few examples of that,” she continued. For example, the massive, global PURE study makes its annual ESC showing with two presentations during Hot Line 5. There’s also a population-wide salt substitution study from Peru and HOPE 4, a community-based hypertension program administered by nonphysicians in Canada, Columbia, and Malaysia, both slated for presentation during Hot Line 3.

“On the one hand, we need to think about innovation, but innovation is not only a new device,” Casadei observed. “Innovation is also how do we do what we do in a better and more efficient way that will afford a wider coverage.”

Inclusiveness, Diversity, and an Eye to the Future

Notable at this year’s congress is the prominence of women in leadership roles: the current presidents of both the ESC (Casadei) and the World Heart Federation—Karen Sliwa, MD, PhD (University of Cape Town, South Africa)—are women, as is one of the two ESC 2019 program chairs.

Both Roffi and Casadei acknowledged to TCTMD that this gender mix is relatively novel at a major international cardiology meeting and part of an ongoing effort on the part of the ESC and other cardiology organizations to be more inclusive. 

“The European Society of Cardiology recognizes the importance of diversity, geographical representation, and gender representation and the program committee has done their very best to fulfill those ambitions,” Casadei told TCTMD.

Like last year in Munich, the congress is also hosting an event for the general public—something Casadei views as “giving back” to the host city. Dubbed “Le cœur de Paris bat plus fort” (the heart of Paris beats stronger), the event will be held on the banks of the Seine outside Hôtel de Ville, Paris’ city hall, and will offer free blood pressure and cholesterol tests, information on CVD prevention and living with heart disease, CPR tutorials, and the chance to wander (virtually) through a 3-D diseased heart.

Casadei hopes it will attract an even larger crowd than the several thousand people who visited the Munich event, and that the importance of the CVD prevention message will sink in for healthcare professionals and the public alike.

“My main concern,” she told TCTMD, “and this is a thread through all of the speeches I will make at this congress, is that we've become too complacent about cardiovascular health and cardiovascular disease. It now is no longer seen as a priority by the drug and device industry, from funders and politicians, and by the people. I think it's time that we go back and reenergize this [discussion] because we are not giving the disease and the burden of this disease the justice and relevance that it deserves.”

TCTMD reporters Todd Neale, Michael O’Riordan, Yael L. Maxwell, and I will be furiously filing stories from the newly revamped Porte de Versailles convention center on Paris’s left bank. Keep up with breaking news around the clock by downloading TCTMD’s new app on your mobile device or follow us on Twitter.