New Guidelines, MI Redefined, and Primary Prevention Aspirin on Stage at ESC Congress 2018

August 20, 2018

MUNICH — At four and counting, Munich, Bavaria's largest city — known for its unique culture and world-class museums, Märzen by the liter, and a history spanning from the sinister to the sublime — is about to tie Barcelona for number of times in the 21st century as host of the European Society of Cardiology (ESC) Congress.  

Topics on tap include new clinical territory for long-term oral anticoagulation, guidance on using increasingly sensitive troponin assays, a handle on patient exposure to radiation during CT angiography, daily primary prevention aspirin in people with risk factors for heart disease, and many others.

Hot Line 1, Sunday, August 26, 14:30-15:45 in Munich (Main Auditorium)

The centerpiece Hot Line presentations launch Sunday afternoon with the Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk (MARINER) randomized, controlled trial (RCT) of rivaroxaban (Xarelto, Bayer/Janssen) in patients who were discharged from a hospitalization and had risk factors for venous thromboembolism (VTE).

The trial randomly assigned more than 12,000 such patients at least 40 years of age who had been hospitalized for an acute illness for at least 3 days to receive the direct oral anticoagulant,  at 10 mg or 7.5 mg, or a placebo for 45 days; they were followed for events for another month.

Those rivaroxaban dosages for primary VTE prevention are lower than the currently recommended levels for reducing the postdischarge risk for recurrent VTE based on the EINSTEIN CHOICE trial.

Scheduled next is the full presentation of the largest-ever RCT of an antiobesity drug, one that demonstrated good cardiovascular (CV) safety in top-line results released last month.

The Cardiovascular and Metabolic Effects of Lorcaserin in Overweight and Obese Patients-Thrombolysis in Myocardial Infarction 61 (CAMELLIA-TIMI 61) study entered a planned 12,000 obese or overweight patients with a history of CV disease, CV risk factors, or type 2 diabetes.

Those randomly assigned to lorcaserin (Belviq, Eisai) instead of placebo showed no significant increase in risk for major adverse cardiac events (MACE), defined as CV death, nonfatal myocardial infarction (MI), and nonfatal stroke.

CAMELLIA-TIMI 61 pursued two other primary endpoints: conversion to type 2 diabetes and MACE plus CV hospitalization; those outcomes had not been included in the reported top-line results. It's a postmarket study in the United States; the drug has been available there since 2012.

The Aspirin to Reduce Risk of Initial Vascular Events (ARRIVE) trial of aspirin for primary CV prevention, which tested 100 mg/day in the face of confusion about the appropriate dosage in this setting, concludes the session. The RCT launched 11 years ago to shed light on one of the field's most persistent questions: whether aspirin at a commonly prescribed daily dosage is cardioprotective in people without a history of CV events.

ARRIVE randomly assigned more than 12,000 adults, middle-aged and older with multiple CV risk factors but no history of vascular events or arrhythmias, to aspirin or placebo. It followed them for about 6 years for CV death, MI, and other vascular events, as well as bleeding.

Hot Line 2, Sunday, August 26, 16:45-17:45, Munich (Main Auditorium)

The spotlight stays with aspirin throughout the first of two presentations focusing on A Study of Cardiovascular Events in Diabetes (ASCEND), with its 2 × 2 randomization of 15,480 patients with type 1 or type 2 diabetes but no history of cardiovascular events or vascular disease.

The trial, launched more than a dozen years ago and expanded midstream because of unexpectedly few clinical events, assigned patients to aspirin, 100 mg/day, or placebo.

In a separate randomization, results of which are to be unveiled in the second of the trial's two presentations, patients received one daily 1-g capsule of 90% omega-3 fatty acids or placebo. 

ASCEND is following patients for a composite endpoint of nonfatal MI, nonfatal stroke or transient ischemic attack, or vascular death, excluding confirmed cerebral hemorrhage (the latter of which was followed as a secondary endpoint).

Joining that trial during the session is the 10-year follow-up of the Arterial Revascularisation Trial (ART), which has compared bilateral to single internal thoracic artery coronary bypass grafting in patients with symptomatic ischemic heart disease.

The trial saw no difference in the primary endpoint of mortality or in a secondary  composite clinical endpoint at the previously reported 5-year follow-up. The ART presentation slated for the ESC sessions promises to divulge the trial's prespecified primary outcome of 10-year survival.

Hot Line 3, Monday, August 27, 11:00-12:30, Munich (Main Auditorium)

This session starts with the Efficacy and Safety of Tafamidis in Transthyretin Amyloid Cardiomyopathy (ATTR-ACT) study, which randomly assigned 441 patients with the rare disorder to the investigational agent or placebo and followed them for a primary endpoint of death or CV hospitalization over 30 months.

In March 2018, the sponsor Pfizer announced that the trial had "met its primary endpoint" by showing a significant reduction in death or CV hospitalizations on active therapy. Tafamidis has been granted orphan-drug status by US and European regulators, Pfizer said.

Patients with transthyretin amyloid cardiomyopathy show a build-up of amyloid bodies in heart muscle caused by abnormal deposition of transthyretin, a protein that normally transports thyroxine and retinol.  

Next on the schedule is an RCT exploring one of the frontiers of heart failure (HF) management. The COMMANDER HF trial is billed as a randomized study comparing rivaroxaban with placebo in patients with HF and significant coronary artery disease after an episode of decompensated HF.

Importantly, the trial's recently discharged patients with ischemic HF with reduced ejection fraction did not have other indications for oral anticoagulation, such as atrial fibrillation (AF). Such patients represent a huge population of people who are not currently candidates for chronic oral anticoagulation.

COMMANDER HF followed the patients assigned to rivaroxaban at 2.5 mg twice daily or placebo for 4 to 5 years for the primary endpoint of death, MI, or stroke and for fatal or potentially disabling bleeding.

In the following presentation slot, the MITRA-FR study is exploring transcatheter mitral valve repair (TMVR) using the MitraClip system (Abbott Vascular) in patients with secondary mitral regurgitation, an ejection fraction between 15% and 40%, and a recent history of  hospitalization for HF.

The RCT randomly assigned 288 such patients at centers in France to optimal medical therapy with vs without MitraClip TMVR and followed them for up to 24 months for death and HF hospitalizations.

The MitraClip system has been available in some form for 10 years in Europe and for 5 years in the United States.

MITRA-FR is scheduled to be followed by the GLOBAL LEADERS trial, which randomly assigned about 16,000 patients to two antiplatelet regimens after undergoing coronary or bypass graft stenting with BioMatrix (Biosensors International) drug-eluting stents (DESs).

The patients were "all comers" for the procedure; eligibility called for at least one lesion with greater than 50% stenosis in a vessel with a reference diameter of at least 2.25 mm; patients with acute coronary syndromes (ACS) were included.

They were randomly assigned to either (1) dual antiplatelet therapy (DAPT) with aspirin and ticagrelor (Brilinta/Brilique, AstraZeneca) for a month, followed by ticagrelor alone for 23 months, or (2) a year of the same DAPT (substituting clopidogrel for ticagrelor in patients with stable coronary disease) followed by a year of aspirin alone.

Patients were followed for 2 years for the primary endpoint of death or new Q-wave MI.

Hot Line 4, Tuesday, August 28, 11:15-12:45, Munich (Main Auditorium)

The Tuesday midday session is scheduled to start with a new analysis from the Prospective Urban Rural Epidemiology (PURE) study, which surprised many and rankled others at the ESC sessions a year ago when it unveiled some iconoclastic findings about diet in a cohort of about 135,000 people in 18 countries.

In particular, it found limits to the benefits conferred by fruits, vegetables, and legumes in the diet and better survival with greater intake of fat, including saturated fat.

This year's report from PURE is described as "association of dietary quality and risk of cardiovascular disease and mortality in more than 218,000 people from over 50 countries."

PURE is tracking diet; health-related behaviors; and environmental, socioeconomic, and other factors in a planned cohort of more than 200,000 adults in countries around the world, industrialized and developing. The longitudinal study expected to last until 2030 is following the cohort for CV death, MI, stroke, and heart failure.

The next scheduled presentation is on the Febuxostat for Cerebral and Cardiorenovascular Events Prevention Study (FREED), which randomly assigned a  planned 1000 patients age 65 years and older with hyperuricemia with risk factors for vascular disease to receive or not receive the gout drug febuxostat (Uloric, Takeda Pharmaceuticals). There was no placebo control.

The cardiovascular safety of febuxostat has been questioned on the basis of the CARES trial, which compared it to allopurinol in patients with gout.

In FREED, patients were followed for cerebral and cardiorenovascular events, which include death, CV and cerebrovascular events, HF, renal impairment, aortic aneurysms or dissection, and new AF.

Next, the open-label Basel Stent Kosten Effektivitäts Trial Drug Eluting Balloons vs Drug Eluting Stents in Small Vessel Interventions (BASKET-SMALL-2) compared the paclitaxel-eluting SeQuent Please (B. Braun Medical) balloon to a DES in 758 patients. The targets were de novo lesions in coronary vessels 2.0 or more mm to less than 3.0 mm in diameter associated with silent or symptomatic ischemia.

The comparator DES could be the paclitaxel-eluting Taxus Element (Boston Scientific) or the everolimus-eluting Xience (Abbott Vascular). Patients were followed for MACE at 12 months.

Rounding out the session, the Very Early vs Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes (VERDICT) was to enter an estimated 2500 patients in Denmark with suspected non-ST-segment elevation ACS and follow them 3 years for MACE.

Management assignments consisted of invasive evaluation and possible revascularization within 12 hours of diagnosis compared to a control strategy that deferred invasive evaluation for 72 hours. VERDICT is also evaluating CT for selecting patients for intervention.

Hot Line 5, Tuesday, August 28, 14:30-15:45, Munich (Main Auditorium)

The High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome (High-STEACS) trial enrolled 48,282 patients with ACS at centers in Scotland and randomly assigned them to evaluation by the high-sensitivity troponin I assay ARCHITECT STAT (Abbott Diagnostics) in stepped-wedge clusters with 6-month vs 12-month validation phases. The study has followed them for CV death or recurrent MI at 1 year.

The Partial Oral Treatment of Endocarditis (POET) sought to determine whether patients with infective endocarditis, who would normally undergo a prolonged course of parenteral antibiotics, might just as effectively be switched to oral antibiotics after a short course of the parenteral agents.

POET entered 400 stable patients with left-sided bacterial endocarditis who had completed at least 10 days of standard parenteral antibiotic therapy and assigned them to continued standard management or a switch to oral antibiotics.

The trial followed them for 6 months for the composite primary endpoint of death, unplanned cardiac surgery, embolic events, or relapse of positive blood cultures with the primary pathogen.

On the schedule after POET, the Aortic Irbesartan Marfan Study (AIMS) entered a projected 490 patients in the United Kingdom aged 6 to 40 years with Marfan syndrome and an aortic-root diameter in the highest 5% of normal. They received  irbesartan (initially 75 mg/day, escalating to 300 mg/day after 2 months) or placebo and were followed for 5 years for absolute change in aortic-root diameter.

AIMS follows an RCT with 608 similar patients with Marfan syndrome in the United States that in 2014 found no significant advantage to another angiotensin-receptor blocker, losartan, over more standard therapy with the β-blocker atenolol for effect on aortic-root dilatation.

Late Breaking Science in Interventional Cardiology 1, Saturday, August 25, 11:00-12:30, Centre Stage (The Hub)

Part of a series of diverse late-breaking registry and other study presentations throughout the congress, the  Transcatheter Valve Therapies Registry Mitral Module (TMVR registry) entered an estimated 4000 patients undergoing the procedure since 2013 for issues including bioprosthetic valve degeneration, failed annuloplasty rings, and severe mitral annular calcification. It is sponsored by the Society of Thoracic Surgeons (STS) and the American College of Cardiology (ACC).

Next, the Canadian Spontaneous Coronary Artery Dissection (SCAD) study prospectively followed 750 children and adults with documented coronary dissection and troponin-positive ACS. It followed them for in-hospital major adverse events and for MACE out to 3 years.

The session will also feature 1-year outcomes from the Culprit Lesion Only PCI vs Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial. The trial made waves last year with the release of its 30-day outcomes, in which mortality with acute intervention limited to the culprit coronary artery in cardiogenic shock was significantly lower than with more aggressive multivessel intervention.

Late Breaking Pharmacological Science, Saturday, August 25, 11:00-12:30, Bratislava (Village 2)

The session includes a report from the Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease (CLARIFY), billed as a presentation of long-term clinical outcomes on first-line anti-ischemic agents. The registry is described as having entered 32,954 patients from 45 countries with a history of MI, bypass graft surgery, angiographic coronary disease, or documented myocardial ischemia.

Also, it features a follow-up analysis from the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, which famously saw a further significant reduction in CV events from treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab (Repatha, Amgen) in patients already receiving statins.

The new analysis of FOURIER patients with metabolic syndrome follows an analysis from the trial last year showing that PCSK9 inhibitor wasn't associated with increased glycemia or diabetes risk.

Late Breaking Science in Imaging, Saturday, August 25, 13:30-15:00, Baku (Village 5)

The Prospective Multicenter Registry on Radiation Dose Estimates of Cardiac CT Angiography in Daily Practice in 2017 (PROTECTION VI) entered an estimated 5500 patients slated for CT angiography. Its stated aim has been to evaluate contemporary measures for minimizing radiation exposure to patients in daily practice and to look for any effects on image quality.

Also scheduled in the session is a presentation from the Assessing Diagnostic Value of Non-Invasive FFRCT in Coronary Care (ADVANCE) registry, aiming to follow an estimated 5000 patients for 3 years for the effect of the CT-based fractional-flow reserve assessments on patients' management plans and for outcomes.

Late Breaking Registry Results 2, Tuesday, August 28, 14:30-15:45, Centre Stage (The Hub)

The prospective Global Anticoagulant Registry in the Field-Atrial Fibrillation (GARFIELD-AF) has a target enrollment of 55,000 patients with nonvalvular AF, plus one additional stroke risk factor, at more than 1000 diverse centers in 35 countries. They are tracked for at least 2 years for mortality as well as embolic events, HF, bleeding, and other outcomes.

The study launched in 2009 and reached its scheduled completion this year; a 2012 report covered results based on the first 10,000 patients entered.

There are two GARFIELD-AF presentations in the lineup, one billed as covering the comparative effectiveness of the oral anticoagulants used in the study and the other addressing 1-year outcomes.

Late Breaking TAVI Registries, Tuesday, August 28, 16:45-17:45, Munich (Main Auditorium)

Included in the session are updates from the prospective, multicenter Low-Risk TAVR (LRT) trial, which is entering candidates for transcatheter aortic valve replacement (TAVR) using various valves in patients with symptomatic, severe aortic stenosis who are considered low risk based on an STS score of 3 or less. The historical control group consists of propensity- and site-matched patients who underwent surgical aortic valve replacement.

Also included is a report from the German Aortic Valve Registry (GARY), which is prospectively entering an estimated 100,000 patients who have undergone TAVR, surgical aortic valve replacement, aortic valve surgical repair, or aortic valvuloplasty and following them for short- and long-term mortality.

On the schedule too is a 5-year follow-up analysis from the French Aortic National CoreValve and Edwards Registry (FRANCE-2), which prospectively tracked all TAVR procedures on high-risk patients in France at 34 centers from 2010 to 2012.

Fourth Universal Definition of Myocardial Infarction, Monday, August 27, 16:45-17:45, Munich (Main Auditorium)

It's been 6 years since release of the 2012 Third Universal Definition of MI, also at an ESC Congress and also in Munich. To update the field after recent important new developments and insights, the Fourth Universal Definition of MI will be unveiled at the ESC Congress.

As recently previewed by a top member of the development committee, the new document holds onto the established five subtypes of MI but attempts to differentiate different forms of "myocardial injury," characterized by a lack of ischemia, based partly on blood troponin dynamics. It elaborates on Takotsubo cardiomyopathy, a form of myocardial injury that can mimic ST-segment elevation MI, wrote Joseph S. Albert, University of Arizona, Tucson, on July 15 in the American Journal of Medicine.

The document also updated the fast-changing arena of high-sensitivity troponin for MI diagnosis and risk stratification and describes MI with nonobstructed coronary arteries (MINOCA). Its pathophysiology remains a mystery despite a number of proposals, including vasospasm, embolism, and hypercoagulable state, the article noted.

2018 Guidelines for the Management of Arterial Hypertension, Sunday, August 26, 11:00-12:30, Munich (Main Auditorium)

New guidelines for the management of arterial hypertension developed jointly by the ESC and the European Society of Hypertension (ESH) are to be published during the ESC Congress to coincide with a live presentation of highlights.

The new document is noteworthy for holding on to previous blood pressure definitions for tiers of hypertension severity that predate and are less strict than those advanced in the controversial 2017 US guidelines developed jointly by the ACC, American Heart Association, and other societies.

The new ESC/ESH guidelines were previewed in June at the latter society's 28th European Meeting on Hypertension and Cardiovascular Protection.

Other Guidelines Sessions, Munich (Main Auditorium)

The 2018 guidelines on myocardial revascularization will be highlighted Monday starting at 08:30 and running until 10:00. They are sponsored jointly by the ESC and the European Association for Cardio-Thoracic Surgery (EACTS).

A session later that day in the same room, from 14:30 to 15:45, will feature the 2018 ESC guidelines on CV disease during pregnancy, covering CV risk stratification, management of arrhythmias and hypertensive disorders, and how to approach pregnancy in women with congenital heart disease.

European Society of Cardiology Congress 2018. August 25 to 29, 2018, Munich, Germany. #ESCCongress2018

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