Paris, Essais Cliniques Très Chic, and New Guidelines Among Charms of ESC Congress 2019

August 26, 2019

It has been something of a tease in recent years when Paris hosted the European Society of Cardiology (ESC) annual end-of-summer sessions at the Parc des Expositions in the northern suburb of Villepinte. Not this year: ESC Congress 2019 kicks off August 30 at the Paris Expo Porte de Versailles, in the heart of the city and almost in the shadow of the Eiffel Tower.

With the new venue will come fresh perspectives on cardiology practice in Europe, as the ESC is set to unveil a raft of new guideline documents at special sessions throughout the meeting, They'll include recommendations on lipid management, the overlap of diabetes and cardiovascular (CV) disease, and chronic coronary syndromes, the recently introduced European moniker for stable coronary artery disease.

Planners of ESC Congress 2019 wanted to launch the first of six center-stage Hot Line sessions with a bang, highlighting several trials of "utmost clinical importance," including a few in the first Hot Line session that had already tipped their hand with announcements of brief "top-line results," Marco Roffi, MD, observed for theheart.org | Medscape Cardiology.

Roffi, of University Hospital of Geneva, Switzerland, is one of the meeting's two program committee chairs; the other seat is filled by Silvia Priori, MD, PhD, University of Pavia, Italy. In an interview, Roffi noted assuredly that the Hot Line time slots allot generous time for volleys of questions and answers, so each trial can be discussed "at length."

Also new this year, Roffi said, the ESC sessions are joined by the World Congress of Cardiology (WCC) 2019, which is departing from its every-2-years solo meeting format to be held annually in conjunction with other major cardiology meetings, it announced last year.

In line with that collaboration, the combined congress has taken on "global cardiovascular health" as its theme, with recognition that "the majority of cardiovascular death today occurs in low- and middle-income countries," Roffi said.

Fittingly, there are Hot Line presentations with that very focus, including one from Peru described as "salt substitution and community‑wide reductions in blood pressure and hypertension incidence," and a HOPE-4 study of hypertension in middle-income countries; both are slated for Monday.

Tuesday will bring two analyses from the multinational PURE study: one looking at the "impact of modifiable risk factors on CV disease" and another at CV disease and cancer epidemiologic patterns in high- and low-income countries.

Hot Line Session 1, Sunday 14:30–15:50

Two presentations on the randomized THEMIS trial — "one of the largest studies of diabetes with respect to antithrombotic treatment," Roffi said — are on the ESC main stage Sunday. The international study tested the antiplatelet ticagrelor (Brilinta/Brilique, AstraZeneca) with vs without aspirin for secondary CV prevention in patients with type 2 diabetes and documented coronary disease.

One of the presentations is to cover overall results; the other will describe outcomes in the subset of the more than 19,000 patients with a history of percutaneous coronary intervention (PCI).

The trial tantalized earlier this year with an announcement that it "met its primary end point" of CV death, MI, or stroke. The notice said little about the trial's balance of antiplatelet efficacy vs safety, especially bleeding, Roffi noted.

Next in the session: the PARAGON-HF trial, which evaluated sacubitril/valsartan (Entresto, Novartis) in the clinically frustrating arena of heart failure with preserved ejection fraction (HFpEF). Novartis recently gave the world a peek at its main result, announcing that the trial "narrowly missed" its primary outcome of CV death or heart failure hospitalization.

The company statement hinted at possibly favorable secondary findings, saying: "The totality of evidence from the trial suggests that treatment with sacubitril/valsartan may result in clinically important benefits in HFpEF."

If true, there may be reasons to give PARAGON-HF more attention than the average "negative" randomized trial. Roffi pointed out that the study is large among heart-failure trials, with more than 4800 patients. Also, "we are lacking efficacious treatments for patients with heart failure and preserved ejection fraction, and it's really an epidemic."

In the DAPA-HF trial, a late addition to the Hot Line 1 schedule, more than 4700 patients with heart failure and a left ventricular ejection fraction (LVEF) of 40% or lower were randomly assigned to receive dapagliflozin (Farxiga/Forxiga, AstraZeneca) or placebo.

The study is noteworthy for testing an antidiabetic agent for cardiovascular end points in heart failure patients with or without type 2 diabetes; patients with type 1 diabetes were excluded.

It comes on the heels of recent DECLARE-TIMI 58 findings of reduced risk for heart failure hospitalization in patients with type 2 diabetes who took dapagliflozin, regardless of their LVEF.

The DAPA-HF sponsor announced top line results only last week. The trial "met" its primary end point by showing a significant and "clinically meaningful" reduction in its composite primary outcome of CV death or hospitalization or "urgent visit" for heart failure in the dapagliflozin group, said AstraZeneca.

Also in the session: the COMPLETE trial randomized more than 4000 patients with multivessel disease to culprit-lesion-only stenting for acute ST-segment elevation myocardial infarction (STEMI) with vs without subsequent staged complete revascularization.

That is, Roffi said, it's about "whether and how you should treat patients with STEMI and multivessel disease but not with cardiogenic shock." That distinguishes COMPLETE from the CULPRIT-SHOCK study presented at last year's ESC sessions, which gave a boost to culprit-lesion-only revascularization in patients with cardiogenic shock.

Hot Line Session 2, Sunday 16:40–17:52

This session opens with the New Zealand Oxygen Therapy in Acute Coronary Syndromes (NZOTACS) trial, which compared "high-oxygen" and "conservative-oxygen" strategies in more than 10,000 patients with acute coronary syndrome (ACS).

Patients in the high-oxygen group received supplemental oxygen regardless of oxygen saturation levels, starting in the field before hospital arrival; those in the conservative group received oxygen only if they were hypoxic.

Supplemental oxygen used to be the "default treatment" in the broad range of ACS, Roffi pointed out, but "more and more data showed that if the patient is not hypoxemic, there isn't much benefit." Other data have suggested the treatment may even harm.

Among oxygen therapy studies, "this is really the largest, by far," Roffi said, "so we are really excited about the results of the study."

Roffi singled out the session's presentation of the ISAR‑REACT 5 trial, a comparison of daily ticagrelor vs prasugrel (Effient, Efient, Lilly/Daiichi-Sankyo) in patients hospitalized with STEMI or ACS with planned invasive management.

Both antiplatelet agents were previously compared with clopidogrel in ACS, Roffi said: ticagrelor in the PLATO trial and prasugrel in TRITON-TIMI 38, both industry-sponsored trials from a decade or more ago. "But nobody so far has ever, in an adequately sized trial, compared the two drugs."

ISAR-REACT 5, which is not industry-funded, includes a second randomization in a subset of patients that assigns them to antiplatelet therapy started prior to intervention or later on, Roffi said.

"This trial will try to answer two questions. One, is one drug better than the other? Two, is ticagrelor pretreatment of benefit or not?" Prasugrel pretreatment in ACS, he added, was previously seen to increase bleeding complications in the ACCOAST trial.

The session is also to include CONDI‑2/ERIC‑PPCI, a randomized exploration of remote ischemic conditioning, using a proprietary system (autoRIC, CellAegis Devices), compared with standard management in 5413 patients undergoing PCI for STEMI

The trial, with its primary end point of cardiac death or heart failure hospitalization at 1 year, features a sham control version of the remote ischemic preconditioning procedure for the standard-management group.

In the first of two Hot Line presentations on cardiac troponin measurements by high-sensitivity assay (hs-Tn) for acute-MI rule out, the ongoing HiSTORIC trial is randomly assigning about 39,000 patients at six centers. Its stepped-wedge cluster randomization scheme has the emergency departments crossing over between standard care and a management pathway with serial hs-Tn measurement, so each center provides their own control phase.

Hot Line Session 3, Monday 11:00–12:30

The session includes HOPE 4, with its epigrammatic description: "Impact on cardiovascular risk of a community‑based multifaceted intervention in individuals with hypertension in two middle income countries."

It also features AFIRE, which randomized about 2200 patients with both coronary disease and atrial fibrillation (AF) to receive rivaroxaban (Xarelto, Bayer/Janssen Pharmaceuticals) with vs without addition of an antiplatelet agent — which could be aspirin, clopidogrel, or prasugrel.

Its primary end points are change in Framingham Risk Score at 1 year and the composite of CV death, CV hospitalization, onset of heart failure, revascularization, and end-stage renal disease at 6 years.

Also in the session: the randomized, 770-patient GALACTIC trial, billed as an exploration of goal‑directed afterload reduction in acute decompensated heart failure; a study of the use of a low-sodium, high-potassium salt substitute by adults in Tumbes, Peru and its effect, if any, on blood pressure in the community; and a presentation entitled, "Combined effect of lower LDL‑C and lower SBP [systolic blood pressure] on the lifetime risk of cardiovascular disease."

Hot Line Session 4, Monday 16:40–17:52

This session features a 2-year follow-up analysis of MITRA-FR, which previously saw no significant primary-outcome advantage to using the transcatheter MitraClip (Abbott) in patients with functional mitral regurgitation compared with medical therapy alone.

Mitral regurgitation tended to be much less severe overall in MITRA-FR patients than in those in the COAPT trial, which showed a strikingly significant reduction in heart failure hospitalizations at 2 years using MitraClip.

"Nevertheless, I think there was disappointment at the 1-year presentation of the MITRA-FR study," said Roffi, and some held hope that a MitraClip advantage would emerge with longer follow-up. So for patients like those in the study, "the 2-year data should tell us which direction we should go in."

Also in the afternoon session: the BB-META-HF study, actually a patient-level meta-analysis of smaller randomized heart failure trials that compared beta-blocker therapy with a placebo-control regimen. The analysis involved 18,240 adults and children; subgroup analyses are a planned highlight of the study protocol.

Following BB-META-HF is the observational SYNTAX Extended Survival (SYNTAXES) study, which tracked patients in the SYNTAX family of randomized trials and registries for 10 years. Patients in those studies underwent either PCI or coronary bypass surgery for angiographically significant three-vessel or left-main coronary disease.

And for those nostalgic for the days of randomized comparisons of PCI and thrombolytic therapy in acute STEMI, the session concludes with 16-year follow-up results from the Danish Acute Myocardial Infarction 2 (DANAMI-2) trial.

The study was noteworthy, in a bygone era, for demonstrating superior results for primary PCI despite delays for hospital transfer of patients to centers with interventional cath labs.

Hot Line Session 5, Tuesday 11:00–12:40

The implantable cardioverter-defibrillator (ICD) is under scrutiny lately for its value in patients with heart failure, regardless of etiology. "The strength and solidity of recommendations for ICDs in the guidelines is based on old trials," Roffi observed.

Those trials in general were conducted when medical treatment options for heart failure were fewer and less sophisticated than today, and before cardiac resynchronization therapy (CRT) was common.

"So the question is whether the benefit that was clear at the time the trials were done is still there on the background of heart failure treatment that has completely changed," he said.

The morning session features a prospective study aimed at the question. Observational but with propensity-matching, it looked at the ICD survival effect in a more contemporary population of patients with heart failure. Still, Roffi cautioned, new randomized trials are needed to really pin down the answer.

Also in the session: the PURE analysis of CV disease and cancer outcomes across the world,; and 5-year results from the CLARIFY prospective longitudinal registry study of patients with stable coronary disease. The latter presentation is informatively titled, "In stable coronary disease, patients with angina and prior myocardial infarction have a poor prognosis despite adherence to guideline recommended therapies."

CLARIFY is to be followed by a SWEDEHEART registry analysis with a focus on "secondary prevention after coronary artery bypass surgery and long‑term mortality." The session also includes a propensity-matched comparison of balloon-expandable and self-expandable transcatheter aortic valve replacement (TAVR) valves based on the FRANCE‑TAVI registry.

Hot Line Session 6, Tuesday 16:40–17:52

Fifteen years after the DINAMIT trial argued against early ICD implantation after an acute MI, another study enrolling at about the same time — in which patients received such a device soon after PCI for STEMI — will update its long-term results.

The Defibrillator After Primary Angioplasty (DAPA) trial, with enrollment halted early at less than half its target, over the next decade saw significantly fewer deaths among its patients receiving vs not receiving an ICD within 2 months of primary PCI. Did the ICD advantage grow with even longer follow-up?

Also in the session: insights on the potential role of newer direct oral anticoagulants in patients with AF who undergo PCI. The ENTRUST‑AF PCI randomly assigned about 1500 such patients to subsequently receive either edoxaban (Savaysa, Daiichi Sankyo) or a vitamin K antagonist, the latter paired with an antiplatelet agent. Its primary end point is major or clinically relevant nonmajor bleeding.

Others in the session include RAPID‑TnT, a second trial on high-sensitivity troponin evaluation of ACS, which showcases a "one-hour protocol"; and POPular Genetics, a randomized open-label trial looking at the cost effectiveness of "genotype‑guided oral P2Y12‑inhibition" in patients getting PCI for STEMI.

2019 ESC Guidelines, Sunday to Wednesday, Main Auditorium

Detailed presentations on the new practice guidelines sponsored by the ESC, in some cases with other European societies, are slated for morning sessions on each day of the congress. They start with an all-encompassing preview at 8:30 on Sunday.

One of the new guidelines, sponsored by the ESC with the European Association for the Study of Diabetes (EASD), covers CV aspects of pharmacologic therapy of diabetes and prediabetes — but not, Roffi said, potential roles for antidiabetic agents in nondiabetics with CV disease.

Other new guideline statements cover treatment of supraventricular tachycardia, excluding AF, and acute pulmonary embolism.

Another covers chronic coronary syndrome, which is the "new" stable coronary disease in European nomenclature, Roffi said. The new term "better underscores the fact that being stable is just another phase of the disease. The syndrome is still there, but one can be in the stable phase or acute."

Finally, there is new statement on management of dyslipidemia, developed by the ESC with the European Atherosclerosis Society (EAS).

"Everyone is eagerly awaiting what will be the role of the PCSK9 inhibitors in that new guideline," Roffi said, referring to the recently introduced but not widely adopted lipid-lowering agents alirocumab (Praluent, Sanofi/Regeneron) and evolocumab (Repatha, Amgen).

Roffi was asked whether the new lipid-management statement will be mostly consistent with or perhaps at odds with a corresponding guideline introduced last year by the American Heart Association (AHA) and American College of Cardiology (ACC). Mindful of embargoes, he replied, "I cannot tell you."

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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