Dec
2
2:00 PM14:00

WHY SOME CLINICAL TRIALS DO NOT WORK OR HAVE AN IMPACT. ARE THERE WAYS TO DO A BETTER JOB? An International Society of Cardiovascular Pharmacology (ISCP)-CVCT joint session

Chairpersons: Angeles Alonso (London, GBR), Milton Packer (Dallas, USA)
2.00 pm – 6.30 pm
 The structure of a large international clinical trial is complex. It typically involves a
sponsor, a leadership committee, numerous geographically-dispersed
investigators, and a group responsible for operational functions.
 A pharmaceutical executive or academic leader must decide whether to propose
a very large expensive clinical trial to upper management. The data supporting
the drug is marginal. He/she advocate strongly for investment, emphasizing data
that are hopeful but minimizing risks.
 The leadership committee defines the trial hypotheses and the methods by which
the hypotheses can be tested in an unbiased manner. Members focus on the big
picture, but do they really know how the trial is being executed?
 Most sponsors lack internal resources to execute the trial and thus seek help from
an outside vendor, a CRO. Their procurement office provides the contract to the
lowest bidder.
 The CRO is itself a business enterprise, which has a responsibility to carry out the
trial in a manner financially advantageous to its owners or shareholders. They
identify investigators who can recruit quickly and inexpensively.
 The investigators are paid to recruit patients. Some are very creative in enrolling
patients very quickly. When the trial is over, they will receive little academic credit,
but will rapidly move on to the next trial.
 The operations group is charged with ensuring that patients are recruited into the
trial on schedule and that the data quality can be made to appear to be
reasonable.
 The data are collected, but the analysis unit understands that certain results will
yield predictable benefits. If this is a phase II trial, a trial yielding positive results
is likely to be followed by additional substantial investment in more studies.
 If this is a phase III trial, the results are rarely satisfying; i.e., the trial’s primary
hypothesis has proven to be valid, and the supporting data are of very high
quality. Much more often than not, both the leadership committee and the
sponsor are disappointed by the results. There may be some positive signals, but
one can find them only after a very diligent and creative search.
 The results of the trial are presented, and internet scavengers emerge from their
hiding places to feast. If the trial is markedly positive, these vultures seek
perceived flaws or hold the trial’s conduct to unrealistic standards. If not, they
demand replication (even if it is unethical or not feasible). If the results are
disappointing, they rejoice in their claims that they predicted the trial’s failure.
 The results of the trial are published. How should a new study be interpreted?
Many physicians do not even make an attempt to read and understand the
primary publication; often they wait for the chatter on the internet or official
guidelines to tell them what to do. Physicians have insufficient knowledge, time or
motivation to perform a proper evaluation.

An overview of the problem seen from the US
Milton Packer (Dallas, USA)
How do sponsors make a decision to support a trial?
David Kallend (The Medicine Company, USA)
Kenneth Stein (Boston Scientific, USA)
Can academic leaders oversell an idea?
Paul Armstrong (Edmonton, CAN)
Karl Swedberg (Gotheborg, SWE)
Who should be minding the store?
Janet Wittes (Statistics Collaborative, USA)
Why do I sometimes have trouble sleeping at night?
Scott Solomon (Boston, USA)
Are academic investigator becoming extinct?
Bertram Pitt (Ann Arbor, USA)
Which types of investigative sites do regulators worry about?
Norman Stockbridge (FDA, USA)
Are practitioners paying any attention to the results of trials?
Antoni Martínez-Rubio (Barcelona, ESP)
What do journal editors think of professional cynics?
Stuart Spencer (The Lancet, GBR)
John Jarcho (NEJM, USA)
Joe Hill (Circulation, USA)
Robert M. Golub (Jama, USA)
Are payers happy when a trial shows a benefit of an expensive drug?
Leeza Osipenko (NICE, GBR)
Media Viewpoint: Ron Winslow (Wall Street Journal, USA)

THE FORUM
Moderated discussion with the audience
Chairpersons : Angeles Alonso (London, GBR), Milton Packer (Dallas, USA)
Panelists: Angeles Alonso (London, GBR), Paul Armstrong (Edmonton, CAN), Robert M.
Golub (Jama, USA), Joe Hill (Circulation, USA), Larry Husten (CardioBrief, USA), John
Jarcho (NEJM, USA), David Kallend (The Medicine Company, USA), Antoni Martínez-
Rubio (Barcelona, ESP), Leeza Osipenko (NICE, GBR), Milton Packer (Dallas, USA),
Bertram Pitt (Ann Arbor, USA), Scott Solomon (Boston, USA), Stuart Spencer (The
Lancet, GBR), Kenneth Stein (Boston Scientific, USA), Norman Stockbridge (FDA,
USA), Karl Swedberg (Gotheborg, SWE), Ron Winslow (Wall Street Journal, USA),
Janet Wittes (Statistics Collaborative, USA)

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Dec
2
2:00 PM14:00

TIME IS MUSCLE. ACUTE INTERVENTION TRIALS IN CORONARY ARTERY DISEASE AND IN HEART FAILURE

Chairpersons: Roxana Mehran (New York, USA), Alexandre Mebazaa (Paris, FRA)
2.00 pm – 6.30 pm
1. Advances and remaining gaps in the early management of acute coronary
syndromes
· How early is early? Chest pain characteristics and opportunities for very
early management from contemporary databases.
Speaker : Patrick Badertscher (Basel, CHE)
Discussant : Justin Ezekowitz (Alberta, CAN)
· Pre hospital, pre PCI intervention. Review of the evidence: Did ATLANTIC
and ACCOAST really fail?
Roxana Mehran (New York, USA)
· How different is a STEMI from a NSTEMI in their infancy?
Wolfgang Koenig (Munich, GER)
· 10-year trends in time to reperfusion of STEMI patients in France
Tabassome Simon (Paris, FRA)
· Home based detection of cardiac ischemia
Olivier Chételat (Neuchâtel, CHE)
· Industry viewpoint:
Sébastien Roux (Idorsia, CHE)
· Regulatory viewpoint
Ellis Unger (FDA, USA)
2. Advances and remaining gaps in the early management of heart failure
· Early pre-admission diagnosis and management of HF congestion related
dyspnea.
Nicolas Girerd (Nancy, FRA)
· Early therapy in AHF. Rearview and ways forward. How to progress from
proof of concept to outcome trials.
Alexandre Mebazaa (Paris, FRA)
· Diuretic – decongesting strategies trials
Eric J. Velazquez (Durham, USA)

· Industry viewpoint
Shalabh Singhal (BMS, USA)
· Regulatory viewpoint
Robert Temple (FDA, USA)
Patient education : Community intervention (campaign) vs. targeted education of
patients
Holli DeVon (Chicago, USA)
Patient viewpoint : Annemieke Lenselink (The Hague Area, NED); Natascha Van der
Post (Nijmegen Area, NED)
THE FORUM
Moderated discussion with the audience
Chairpersons: Roxana Mehran (New York, USA), Alexandre Mebazaa (Paris, FRA)
Panelists: Patrick Badertscher (Basel, CHE), Olivier Chételat (Neuchâtel, CHE), Holli
DeVon (Chicago, USA), Justin Ezekowitz (Alberta, CAN), Nicolas Girerd (Nancy, FRA),
Wolfgang Koenig (Munich, GER), Annemieke Lenselink (The Hague Area, NED);
Alexandre Mebazaa (Paris, FRA), Roxana Mehran (New York, USA), Sébastien Roux
(Idorsia, CHE), Tabassome Simon (Paris, FRA), Shalabh Singhal (BMS, USA), Robert
Temple (FDA, USA), Ellis Unger (FDA, USA), Natascha Van der Post (Nijmegen Area,
NED), Eric J. Velazquez (Durham, USA)

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Dec
2
8:00 AM08:00

EVALUATION OF NEW TECHNOLOGIES IN CARDIOVASCULAR CARE. BRIDGING EVIDENCE-BASED WITH VALUE-BASED HEALTH CARE A MEDTECH Europe – ADVAMED – CVCT joint session

 Regulators and payers sometimes differ in their perspectives on medical advances
and the weight they place on components of the evidence base. These contrasting
priorities can lead to divergence between regulatory and payer decisions and delays
or barriers in patients’ access to new therapies.
 Those involved in coverage decisions have not routinely been integrated in the drug
development process pre-approval, specifically with respect to clinical trial design.
Inclusion of payer representatives sooner in the development process would provide
opportunities to detect discordance among stakeholders in terms of data priorities,
facilitate cooperation to align objectives, agree on the evidence required for approval
and reimbursement, improve transparency and accountability of payer decision
making, and ideally minimize delays in patient access to new therapies.
 Research on the benefits and performance of devices differs between ‘therapeutic’
devices (e.g. pacemakers, nerve stimulators, prostheses) and ‘non-therapeutic’
devices (e.g. diagnostic, monitoring, screening or prognostic tests).
 “Value-based healthcare”, focuses on outcomes that are relevant to patients,
including, but not limited to, clinical outcomes
 Therefore a linked or network of evidence approach may be better suited to device
evaluations than a ‘hierarchy of evidence’ approach.
 Health ministers in EU recently mandated that the OECD develop an instrument to
collect information (PaRIS) to be able to compare the performance of health
systems, as well as the performance of clinicians and technology.
 MedTech companies and organizations in Europe and the USA currently has
programs in place to drive “value-based healthcare”
 Device evaluations are enhanced when device developers, manufacturers, trialists,
regulators, payers, health professionals and patients collaborate to agree on the
“Burden of proof” and describe at an early stage the potential mechanisms/pathways
through which achieve “value-based healthcare”, ultimately improving timely patient
access to new treatments that reduce the burden of disease or prolong life.
Panel on Evaluation Systems for New Technology: Overview & comparison of
evaluation systems. Discussion on whether certain evaluation systems are better suited
for certain types of devices/ disease states/ healthcare system. Identification of one
evaluation system that is preferred over others.
· Evidence based evaluations of Medical Technology and Biomarkers: what
does it actually mean and what do we want?
o The EU perspective
Karl Moons (Utrecht, NED)

· Medicare Evaluation: What is the process & what evidence is required for
coverage today?
Joseph Chin (CMS, USA)
· Willingness-to-pay: Europe’s Most Economically Advantageous Tender
pilot (MEAT)
Yves Verboven (MedTech Europe, Brussels, BEL)
Panel on Streamlining Clinical Trial Data Collection with Evaluation System
Requirements: Overview & comparison of relevant types of clinical data, with a focus
on how each serves (or does not serve!) one of the respective evaluation systems.
Discussion on why and how evaluation systems must evolve to take such critical data
into account.
· Patient-Reported Outcomes: How should they be valued?
Michael Nassif (Kansas City, USA)
· Real-world data collection: What is the value of this for device therapy?
Dalal Nirav (Abbott, USA)
Industry viewpoint:
Philip Adamson (St Jude, USA), Robin Bostic (Abbot, USA), Julia Stubben (MedTech
Europe, CVRx, CHE), Nadim Yared (AdvaMed, CVRx, USA)
Regulatory viewpoint
John Whyte (FDA, USA), Bram Zuckerman (FDA, USA)
Payers’ perspective:
Joseph Chin (CMS, USA), Leeza Osipenko (NICE, GBR)
.
The Forum. Moderated discussion with the audience
The Role of Payers in Cardiovascular Clinical Research: Addressing the
Misalignment Between Approval and Reimbursement.
Chairpersons: Jeffrey Borer (New York, USA), Nadim Yared (CVRx, USA)
Panelists: Philip Adamson (St Jude, USA), Jeffrey Borer (New York, USA), Robin Bostic
(Abbot, USA), Joseph Chin (CMS, USA), Karl Moons (Utrecht, NED), Michael Nassif
(Kansas City, USA), Dalal Nirav (Abbott, USA), Leeza Osipenko (NICE, GBR), Julia
Stubben (MedTech Europe, CVRx, CHE), Yves Verboven (MedTech Europe, Brussels,
BEL), John Whyte (FDA, USA), Nadim Yared (CVRx, USA), Bram Zuckerman (FDA,
USA)

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Dec
2
8:00 AM08:00

POSITIVE SIGNALS FROM RECENT NEUTRAL HEART FAILURE TRIALS: TIME FOR AN AUTOPSY HFSA – CVCT JOINT SESSION

Chairpersons: Chris O'Connor (Inova, USA), Mona Fiuzat (FDA/Duke, USA)
8.00 am – 1.00 pm
 So-called “neutral” or “negative” trials contribute to the body of evidence with a
drug, device, or procedure. Such trials often provide relevant knowledge to the
field and often inform planning of subsequent randomized trials.
 When a trial fails to show statistically significant evidence of benefit of an
experimental intervention, the cardiovascular community should ask whether the
intervention worked, but the trial was flawed in some way, or the trial was valid
but the intervention was ineffective.
 The appropriate next steps after completion of an inconclusive trial are influenced
by 1) whether a strong mechanistic or biologic rationale supports use of the
treatment and 2) the overall assessment of potential reasons why the trial did not
meet its primary objective.
 It is crucial, but often difficult, to determine if a clinical outcomes trial did not show
a treatment effect because of errors in trial design or execution or if the treatment
was truly ineffective.
“Autopsy is performed by anatomists with the principal aim of an autopsy is
to determine the cause of death, the state of health of the person before he
or she died, and whether any medical diagnosis and treatment before
death was appropriate.”
 The objective of this session is to have trial specialists examine failed trials with
the aim of determining causes of failure, the robustness of the trials before they
failed, and whether any appropriate early examination or corrective action could
have prevented negative/neutral results.
 The aim is ultimately to draw lessons that may inform the design and the conduct
of future trials. Future trials may be designed addressing lessons learned from
informative but inconclusive trials, applying different patient populations, alternate
treatment regimens, or different outcomes. Alternatively, trials should be viewed
in the broader context of how the results can inform the field.
Introduction
Chris O'Connor

One main reason I believe my trial didn’t meet its primary endpoint:
· RELAX-AHF-2: John Teerlink (San Francisco, USA)
· TRUE AHF: Milton Packer (Dallas, USA)
· TOPCAT: Bertram Pitt (Ann Arbor, USA)
· GUIDE IT: Michael Felker (Durham, USA)
· BLAST: Peter Pang (Chicago, USA)
· Vericiguat in HFpef : Javed Butler (New York, USA)
· HF ACTION: Dave Whellan (Durham, USA)
· BEST: Mike Bristow (Aurora and Boulder, USA)
· SERVE-HF: Faiez Zannad (Nancy, FRA)
Statistical viewpoint
Nancy Geller (NHLBI, USA)
Cyrus Mehta (Boston, USA)
Investigator viewpoint:
Karl Swedberg (Goteborg, SWE)
Industry viewpoint: Jim Carr (Stealth Peptide, USA), Claudio Gimpelewicz (Novartis,
CHE), Johannes Holzmeister (Cardiorentis, CHE); Lothar Roessig (Bayer, GER), James
Strait (Merck, USA)
NHLBI viewpoint:
George Sopko (NHLBI, USA)
CRO viewpoint
Monica Shah (Quintiles, USA)
Patient viewpoint : Natascha Van der Post (Nijmegen Area, NED)
The Forum. Moderated discussion with the audience
What lessons have we learned? How did is success secured in ongoing trials?
Chairpersons: Chris O'Connor (Inova, USA), Mona Fiuzat (FDA/Duke, USA)
Panelists: Mike Bristow (Aurora and Boulder, USA), Javed Butler (New York, USA), Jim
Carr (Stealth Peptide, USA), Michael Felker (Durham, USA), Mona Fiuzat (FDA/Duke,
USA), Nancy Geller (NHLBI, USA), Claudio Gimpelewicz (Novartis, CHE), Johannes
Holzmeister (Cardiorentis, CHE), Allen Kindman (Quintiles, USA), Cyrus Mehta (Boston,
USA), Chris O'Connor (Inova, USA), Milton Packer (Dallas, USA), Peter Pang (Chicago,
USA), Bertram Pitt (Ann Arbor, USA), Lothar Roessig (Bayer, GER), Monica Shah
(Quintiles, USA), James Strait (Merck, USA), George Sopko (NHLBI, USA), Karl
Swedberg (Goteborg, SWE), John Teerlink (San Francisco, USA), Natascha Van der
Post (Nijmegen Area, NED), Dave Whellan (Durham, USA), Faiez Zannad (Nancy, FRA)

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Dec
1
3:30 PM15:30

THE FUTURE OF CARDIOVASCULAR BIOMARKERS: FROM RISK STRATIFICATION TO PRECISION MEDICINE

A Critical Mechanisms Of Disease (CMOD) – CVCT joint session
Chairpersons: Nick Mills (Edinburgh, GBR), Jean Claude Tardif (Montreal, CAN)
3.30 pm – 7.30 pm
 High sensitivity troponins are useful for diagnosis and prognosis in patients with
suspected acute coronary syndrome. Though a large volume of evidence to
support their utility in such settings has been generated, there is a lack of
consensus on the optimal way in which to apply these assays in clinical practice.
Novel, rapid algorithms may hold the key to improved patient care using these
biomarkers, but much remains to be discussed.
 Recent publications have focused the attention of many clinicians on the potential
role for biomarkers of cardiac injury in refining the approach to cardiovascular
(CV) risk stratification in the general population. Whether this will ultimately
change practice remains to be seen.
 Biomarkers may serve to discriminate various substrates for coronary syndromes
and heart failure that could direct individuals to different management strategies.
As such, they may stratify patients mechanistically and therapeutically and might
help achieve the goal of a more precision management and personalized
approach.
 Whether these concepts have gained power and how much are these pertinent to
precision and personalized medicine, and how to incorporate in future CV trials is
a matter of intense debate.
 Lessons learnt from the mixed success of biomarker – guided clinical trials need
to be shared with the aim of refining methodology and moving the area forward
Keynote lecture:
Circulating and imaging biomarkers of atherosclerosis and prospects of
precision management and personalized approach of cardiovascular disease.
Peter Libby (Boston, USA)
Is CV risk modified by therapies and can that be monitored using CV biomarkers?
Nick Mills (Edinburgh, GBR)
The role of biomarkers in detecting risk of cardiac toxicity in cancer trials.
Jean Claude Tardif (Montreal, CAN)
Can high sensitive troponins improve cardiovascular risk stratification in the
general population?
· In EU: Johannes Neumann (Hamburg, GER)
· In US: Christie Ballantyne (Houston, USA)
Risk stratification of suspected ACS patients: Optimal algorithm?
Agim Beshiri (Abbott, USA)

Health Economics and Outcomes impact of risk stratification with novel CV
biomarkers
Amy Durtschi (Abbott, USA)
Imaging to guide HF therapy.
Faiez Zannad (Nancy, FRA)
Biomarker guided therapy trials failed so far. Methodological lessons
Kirkwood Adams (Chapel Hill, USA)
Advancing Precision Medicine: Current and future proteogenomic strategies for
biomarker discovery and development
Ida Grundberg (Olink, USA)
Industry viewpoint: Gillian Murtagh (Abbott, USA), André Ziegler (Roche, CHE)
The Forum. Moderated discussion with the audience
Are we ready for precision CV medicine?
Chairpersons: Nick Mills (Edinburgh, GBR), Jean Claude Tardif (Montreal, CAN)
Panelists: Kirkwood Adams (Chapel Hill, USA), Christie Ballantyne (Houston, USA),
Agim Beshiri (Abbott, USA), Ida Grundberg (Olink, USA), Peter Libby (Boston, USA),
Amy Durtschi (Abbott, USA), Nick Mills (Edinburgh, GBR), Gillian Murtagh (Abbott,
USA), Johannes Neumann (Hamburg, GER), Jean Claude Tardif (Montreal, CAN), Faiez
Zannad (Nancy, FRA), André Ziegler (Roche, CHE)

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Dec
1
to Dec 23

ATRIAL FIBRILLATION TRIALS. A HRS – CVCT joint session

Chairpersons : George Van Hare (Saint Louis, USA), Heather Ross (Tempe, USA)
2.00 pm – 7.30 pm
 Ablation trials
o Current guidelines recommend pulmonary-vein isolation by means of catheter
ablation as treatment for drug-refractory paroxysmal atrial fibrillation.
Radiofrequency ablation is the most common method, and cryoballoon ablation is
the second most frequently used technology.
o It was recently reported that cryoballoon ablation was noninferior to
radiofrequency ablation with respect to efficacy for the treatment of patients with
drug-refractory paroxysmal atrial fibrillation, and there was no significant
difference between the two methods with regard to overall safety. (FIRE AND
ICE).
o It is not known whether successful ablation of AF, regardless of technique, will
result in reduced mortality. This is under investigation in the Catheter Ablation
versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation (CABANA) and
Catheter Ablation versus Standard Conventional Treatment in Patients With LV
Dysfunction and AF (CASTLE-AF)
o However, specifically in persistent atrial fibrillation in patients with heart failure
catheter ablation, whether ablation is superior to amiodarone was examined in a
randomized study which showed that catheter ablation of atrial fibrillation is
superior to amiodarone in achieving freedom from AF at long-term follow-up and
reducing unplanned hospitalization and mortality in patients with heart failure and
persistent AF.
 NOAC trials
o Trials reporting anticoagulant benefits in AF were done in people with either
symptomatic AF or paroxysmal AF long enough to be recorded on multiple ECGs.
o Diagnosis of short term AF is of uncertain significance. It seems that only longerlasting
AF associates with stroke.
o How valuable short-duration AF as a surrogate marker is questionable and needs
further substantiation.
o Guidelines recommendations regarding anticoagulant therapy after percutaneous
coronary intervention (PCI) among patients with atrial fibrillation (AF) rely on
retrospective, nonrandomized observational data. Currently, patients are treated
with triple-therapy (dual antiplatelet therapy [DAPT] + oral anticoagulation
therapy), but neither the duration of DAPT nor the level of anticoagulation has
been studied in a randomized fashion. Recent studies also suggest dual pathway
therapy with clopidogrel plus oral anticoagulation therapy may be superior, and
other studies suggest that novel oral anticoagulants such as rivaroxaban may
further improve patient outcomes.
The PIONEER AF-PCI study is the first randomized comparison of VKA vs. novel
oral anticoagulant therapy in patients with AF receiving antiplatelet therapy after
PCI to assess the relative risks of bleeding complications.

 Left atrial appendage closure trials
After the initial trials and within the context of controversial evidence of efficacy of
the FDA approved Watchman percutaneous left atrial appendage closure (LAAC),
further data are derived from registries. CMS covers FDA approved LAAC for
non-valvular atrial fibrillation through Coverage with Evidence Development
(CED) in patients enrolled in certain well designed registries and in FDA approved
trials. Patients unsuitable for oral anticoagulation are further evaluated with in the
ASAP-TOO trial
 Research on the causes and mechanisms of AF points to the role of fibrosis. Trials
of anti fibrotic agents?
Trials of anti-thrombotic therapy in AF Ablation (AXAFA - AFNET 5 trial)
Paulus Kirchhof (Birmingham, GBR)
NOACs in patients with atrial fibrillation who undergo percutaneous coronary
intervention.
Harry Crijns (Maastricht, NED)
Targeted anticoagulation for short-term device detected AF. Is it ripe for a
prospective NOAC trial?
Renato Lopes (Durham, USA)
The value of trial derived novel biomarker-based bleeding risk score for patients
with AF.
Ziad Hijazi (Uppsala, SWE)
Left Atrial Appendage Closure. Registry non-randomized evidence and how it
aligns with randomized trial evidence
Lucas Boersma (Nieuwegein, NED)
Targeting the right patient population. Are trials addressing personalized AFib
prevention/treatment strategies?
Nassir Marrouche (Salt Lake City, USA)
Vascular closure device to shorten time to ambulation after AF ablation; The
AMBULATE Trial
Mintu Turakhia (Stanford, USA)
Industry perspective
Martin Unverdorben (Daiichi Sankyo, USA), Peter Dibattiste (Janssen, USA), Kenneth
Stein (Boston Scientific, USA)
Regulatory Perspective:
Andrew Farb (FDA, USA), Pieter DeGraeff (EMA, NED)

Benefit/risk and cost effectiveness considerations of anti-thrombotic strategies in
AF. Payers perspective:
Joseph Chin (CMS, USA)
Patient viewpoint : Natascha Van der Post (Nijmegen Area, NED)
Media viewpoint : Ron Winslow (Wall Street Journal, USA)
The Forum. Moderated discussion with the audience
How to progress from evidence generation to change in practice.
Chairpersons: George Van Hare (Saint Louis, USA), Heather Ross (Tempe, USA)
Panelists: Lucas Boersma (Nieuwegein, NED), Joseph Chin (CMS, USA), Harry Crijns
(Maastricht, NED), Pieter DeGraeff (EMA, NED), Peter Dibattiste (Janssen, USA),
Andrew Farb (FDA, USA), Ziad Hijazi (Uppsala, SWE), Paulus Kirchhof (Birmingham,
GBR), Renato Lopes (Durham, USA), Nassir Marrouche (Salt Lake City, USA), Heather
Ross (Tempe, USA), Kenneth Stein (Boston Scientific, USA), Mintu Turakhia (Stanford,
USA), Martin Unverdorben (Daiichi Sankyo, USA), Natascha Van der Post (Nijmegen
Area, NED), George Van Hare (Saint Louis, USA), Ron Winslow (Wall Street Journal,
USA)

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Dec
1
8:00 AM08:00

eTRIALS. OPPORTUNITIES AND CHALLENGES

Chairpersons : Rob Califf (Durham, USA), Bram Zuckerman (FDA, USA)
8.00 am – 1.00 pm
 This session aims at discussing the current state of the use of digital technology
and mobile health in clinical trials in cardiovascular medicine, what data is
available for utilizing digital technology as a supportive tool or an intervention in
clinical trials, and how can digital technology be used to streamline clinical trial
conduct (reduce visits, enrollment/recruitment, subject retention, safety data
collection, “site-less” remote clinical trials).
 Potential outcomes (ex. PRO, HR/BP, and activity trackers) can be used with
digital health. Can these be used for new drug registration trials and/or postmarketing
trials?
 Experts in large IT data platforms will present case studies and discuss what can
be gained in CV clinical trial conduct and what are the barriers/challenges to
utilizing digital technology in global CV clinical trials.
Keynote lecture
Integrating Data Science with Evidence Generation
Rob Califf (Former commissioner, FDA, People centered Research Foundation,
Verily, Durham, USA)
Opportunities and challenges with medical informatics use for clinical trials?
Adrian Hernandez (Durham, USA)
IBM Watson Health
Irene Dankwa-Mullan (IBM, USA)
Health eHeart Study and Health eHeart Alliance
Carol Maguire (San Francisco, USA)
Approach to Virtual Trials (eConsent to ePROs)
Anthony Costello (Medidata, USA)
The National Patient Centered Clinical Research Network (PCORnet)
Adrian Hernandez (Durham, USA)
Issues in the acquisition, analysis, and sharing of data in the field of
cardiovascular science
Elliot Antman (Boston, USA)

How to move from hospital visit and patient reported outcomes to real-life
objective measurements
Pierre-Yves Frouin (Bioserenity, FRA)
Utility of geofencing to capture missing hospitalizations in clinical trials.
Abhinav Sharma (Stanford, USA and Nancy, FRA)
Methodology/statistical viewpoint
Nancy Geller (NHLBI, USA)
Investigator viewpoint
Mintu Turakhia (Stanford, USA)
Industry viewpoint
Helina Kassahun (Amgen, USA), Kenneth Stein (Boston Scientific, USA), Nancy Dreyer
(Quintiles, USA)
Patient's Perspective for Clinical E-Trials
Debbe McCall (Murrieta, USA)
Regulatory viewpoint
Bakul Patel (FDA, USA), Gail Pearson (NHLBI, USA), Krishna Prasad (EMA, GBR),
Bram Zuckerman (FDA, USA)
The Forum. Moderated discussion with the audience
Chairpersons : Rob Califf (Durham, USA) , Bram Zuckerman (FDA, USA)
Panelists: Elliot Antman (Boston, USA), Rob Califf (Durham, USA), Anthony Costello
(Medidata, USA), Debbe McCall (Murrieta, USA), Irene Dankwa-Mullan (IBM, USA),
Nancy Dreyer (Quintiles, USA), Pierre-Yves Frouin (Bioserenity, FRA), Nancy Geller
(NHLBI, USA), Adrian Hernandez (Durham, USA), Stefan James (Uppsala, SWE),
Helina Kassahun (Amgen, USA), Carol Maguire (San Francisco, USA), Bakul Patel
(FDA, USA), Gail Pearson (NHLBI, USA), Krishna Prasad (EMA, GBR), Mintu Turakhia
(Stanford, USA), Kenneth Stein (Boston Scientific, USA), Bram Zuckerman (FDA, USA)

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Dec
1
8:00 AM08:00

EVOLVING APPROACH TO THE CONDUCT OF CARDIOVASCULAR AND RENAL OUTCOME TRIALS IN DIABETES. HOW DO RECENT TRIALS INFORM FUTURE DRUG DEVELOPMENT?

Chairpersons: Bruce Neal (Sydney, AUS); Felipe Martinez (Cordoba, ARG)
8.00 am – 3.00 pm
 Regulatory agencies state that reduction of glycated haemoglobin (HbA1C) is an
appropriate primary endpoint in diabetes drug development, as it reflects glucose
control, and is known to be correlated with a reduced risk of micro vascular
complications.
 Until recently, data have not supported a beneficial effect of improving glycaemia in
diabetes on CV outcomes. Beneficial effects on macro-vascular complications can
only be evaluated properly in large scale and long-term controlled clinical trials, which
are not considered mandatory for marketing authorisation approval.
 In case it is considered necessary to perform a more in-depth assessment of the
cardiovascular safety profile of a new drug intended for the treatment of diabetes,
EMA recommends two approaches: a meta-analytic approach of outcome data
generated in the phase II/III studies, or a dedicated cardiovascular outcome study.
 The FDA guidance recommends a dedicated preapproval CV trial powered to
establish safety by establishing an upper bound of the two-sided 95% confidence
interval below 1.8 with the requirement for a subsequent trial to establish noninferiority
to rule out an upper bound confidence interval exceeding 1.3 for a new drug
intended for the treatment of diabetes.
 Would a more tailored approach, requiring a CVOT depending on the mechanism of
action of a specific drug and based on nonclinical and early phase clinical data be
more appropriate?
 The EMA’s and FDA’s preferred safety endpoint, is a composite of cardiovascular
death, non-fatal myocardial infarction, and non-fatal stroke. Heart failure events occur
with a similar frequency as myocardial infarction and with a greater frequency than
stroke in patients with type 2 diabetes mellitus at high cardiovascular risk. Regulatory
agencies should recommend including heart failure events as endpoints in diabetes
clinical trials, whether evaluating efficacy or safety. Should only heart failure requiring
hospitalization be the CHF endpoint? Should the focus on primary endpoint (3pt
MACE vs CHF) be a function of the mechanism of action of the drug under
development?
 Trials set in compliance with this guidance have occasionally been powered for
efficacy, or efficacy has been tested as part of the statistical hierarchy after CV safety
has been established. If efficacy (superiority over standard of care) has been
established in a trial (as for empagliflozin, liraglutide, and semaglutide), does this
have the same strength of evidence as a trial designed for superiority? Should
criteria for establishing CV efficacy based on a single trial be explicitly described and,
if so, what is an appropriate p value for superiority?
 Some molecules seem to impact atherosclerosis related endpoints, others improve
MACE events with mechanisms other than atherosclerosis, and/or heart failure
related endpoints.
 Trials using agents from the same pharmacological classes produced discrepant
results (LEADER and SUSTAIN6 vs. ELIXA and EXSCEL; SAVOR vs. other DPPIV

trials; EMPA-REG vs. CANVAS raising issues about class effect vs
structural/pharmacokinetic differences between molecules of the same class.
 There are emerging data suggesting an association between severe hypoglycaemia
and death, which should be taken into account in differentiating among new drugs
intended for the treatment of diabetes.
Endpoint related issues
· Non-inferiority cardiovascular safety endpoints in diabetes trials. Are efficacy
endpoint trials preferable.
Steven Nissen (Cleveland, USA)
o Cardiologist viewpoint
Naveed Sattar (Glasgow, USA)
o Diabetologist viewpoint
Steven Marso (Kansas City, USA)
· Should MACE be the primary endpoint in CV diabetes in CV efficacy/safety
outcome trials irrespective of the drug’s mechanism of action?
“Atherosclerosis” endpoints and/or heart failure endpoints.
Faiez Zannad (Nancy, FRA)
· Severe hypoglycemia and all cause mortality in CVOTs- What have we
learned?
Michael Farkouh (Toronto, CAN)
Patient population related issues
· Challenges of primary prevention (CV risk) and limitations of secondary
prevention (history of CV events) target populations?
Bruce Neal (Sydney, AUS)
· Addressing patients with CKD
Vlado Perkovic (Sydney, AUS)
· Going beyond diabetes. Non-diabetes trials of new drugs initially intended for
the treatment of diabetes.
Milton Packer (Dallas, USA)

Methodological issues
· The issue with non-inferiority design and interim analyses. Protecting
subsequent trial conduct during/following an interim analysis
Darren McGuire (Dallas, USA)
· Methodological refinements may help streamline future diabetes trials.
Cyrus Mehta (Boston, USA)
Industry viewpoint:
Elisabeth Björk (AstraZeneca, SWE), Mehul Desai (Janssen, USA), Stephen Gough
(NovoNordisk, DEN), Jyothis George (Boehringer Ingelheim, GER); Erica Caveney
(Quintiles, USA)
Regulatory viewpoint:
Robert Temple (FDA, USA),
NIH viewpoint
Yves Rosenberg (NHLBI, USA)
Payers’ viewpoint: How to value a diabetes drug with CV mortality benefit?
Lorenzo Mantovani (Milano, ITA)
Patient viewpoint : Patrick Gee (Chesterfield, USA)
Media Viewpoint: Ron Winslow (Wall Street Journal, USA)
The Forum. Moderated discussion with the audience
Refining the current regulatory guidance.
Chairpersons: Bruce Neal (Sydney, AUS); Felipe Martinez (Cordoba, ARG)
Panelists: Elisabeth Björk (AstraZeneca, SWE), Erica Caveney (Quintiles, USA), Mehul
Desai (Janssen, USA), Michael Farkouh (Toronto, CAN), Patrick Gee (Chesterfield,
USA), Jyothis George (Boehringer Ingelheim, GER), Stephen Gough (NovoNordisk,
DEN), Larry Husten (CardioBrief, USA), Darren McGuire (Dallas, USA), Lorenzo
Mantovani (Milano, ITA), Felipe Martinez (Cordoba, ARG), Cyrus Mehta (Boston, USA),
Bruce Neal (Sydney, AUS); Steven Marso (Kansas City, USA), Steven Nissen
(Cleveland, USA), Milton Packer (Dallas, USA), Vlado Perkovic (Sydney, AUS), Stuart
Pocock (London, GBR), Susan Quella (Rochester, USA), Yves Rosenberg (NHLBI,
USA), Naveed Sattar (Glasgow, USA), Dan Schaber (Medtronic, USA), Robert Temple
(FDA, USA), Ron Winslow (Wall Street Journal, USA), Faiez Zannad (Nancy, FRA)

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Nov
30
3:30 PM15:30

TRANSCATHETER HEART VALVE THERAPIES TRIALS

Chairpersons: Robert Bonow (Chicago, USA), Ileana Pina (New York, USA)
3.30 pm – 7.30 pm
 Could THV device approval follow a pathway analogous to that of surgical heart
valves by incorporating OPC? Would this be more appropriate only for approval of
new-generation THVs in high- and extreme-risk patient populations?
 Should approval of THV devices for low- and intermediate-risk patients or for new
indications be based on data from randomized, clinical trials?
 How contemporary registries may be useful as a platform for regulatory reform of
cardiovascular devices, for generating data to serve as a comparator arm for future
trials and to establish objective performance criteria? To perform comprehensive,
reliable, and timely post-marketing safety surveillance

 Surgical heart valves can be approved on the basis of objective performance criteria
(OPC). In contrast, stricter criteria for transcatheter heart valve (THV) approval,
including randomized, clinical trials. FDA has recently approved new-generation
THVs based on single-arm studies.
Trial design and endpoint definitions for trans catheter valve trials
Pieter Kappetein (Rotterdam, NED)
When and how to apply to trans catheter valve trials?
Jeffrey Borer (New York, USA)
Industry perspective:
Martyn Thomas (Edwards, USA)
Statistical considerations beyond objective performance criteria.in trans catheter
valve trials?
Mike Boulware (Medtronic, USA)
Insights from Transcatheter Valve Replacement (TAVR) Registries
Ileana Pina (New York, USA)
Registries as a platform for regulatory approval. Are we there yet? What actions
are needed to get there?
Roxana Mehran (New York, USA)
New valve designs, and how large a change in a device requires further clinical
testing?
Danny Dvir (Seattle, USA)
Mitral valve replacement trials and repair
Jeffrey Popma (Boston, USA)

Upstream TAVI in the less sick: when to replace the valve?
Pascal Leprince (Paris, FRA)
NHLBI Perspective.
Marissa Miller (NHLBI, USA)
Industry Perspective.
Patrick Verta (Edwards, USA)
Regulatory Perspective.
John Laschinger (FDA, USA); Bernard Vasseur (FDA, USA), Alan Fraser (Cardiff, GBR)
Payers viewpoint: How far upstream will TAVI be reimbursable? Based on which
evidence?
Tamara Syrek Jensen (CMS, USA); Harindra Wijeysundera (Canadian Agency for Drugs and
Technologies in Health, CAN)
Thrombosis trials in TAVR patients
· Thrombus apposition and valve mobility/durability in TAVR. The rationale
for OAC.
Rajendra Makkar (Los Angeles, USA)
· Industry perspective
Martin Unverdorben (Daiichi Sankyo, USA)
· Regulatory Perspective. Which study designs maybe accepted to obtain
approval of an antithrombotic regimen?
Karen Hicks (FDA, USA)
Patient viewpoint : Stefan Teunis (Oldenzaal, NED)

The Forum: Moderated discussion with the audience
How to tackle the ever-evolving technologies?
How to optimize anti-bleeding strategies?
Chairpersons: Robert Bonow (Chicago, USA), Ileana Pina (New York, USA)
Panelists: Robert Bonow (Chicago, USA), Jeffrey Borer (New York, USA), Mike
Boulware (Medtronic, USA), Danny Dvir (Seattle, USA), Alan Fraser (Cardiff, GBR),
Karen Hicks (FDA, USA), Pieter Kappetein (Rotterdam, NED), John Laschinger (FDA,
USA), Pascal Leprince (Paris, FRA), Rajendra Makkar (Los Angeles, USA), Roxana
Mehran (New York, USA), Marissa Miller (NHLBI, USA), Ileana Pina (New York, USA),
Jeffrey Popma (Boston, USA), Dan Schaber (Medtronic, USA), Tamara Syrek Jensen
(CMS, USA), Stefan Teunis (Oldenzaal, NED), Martyn Thomas (Edwards, USA), Martin
Unverdorben (Daiichi Sankyo, USA), Bernard Vasseur (FDA, USA), Patrick Verta
(Edwards, USA), Harindra Wijeysundera (Canadian Agency for Drugs and Technologies
in Health, CAN),

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Nov
30
2:00 PM14:00

RENAL ENDPOINTS IN CKD, HEART FAILURE AND DIABETES TRIALS. American Society of Nephrology (ASN) - Kidney Health Initiative (KHI) – CVCT Joint session

Chairpersons: Prabir Roy-Chaudhury (Tucson, USA); Patrick Rossignol (Nancy, FRA)
2.00 pm – 3.30 pm / 4.00 - 7.30 pm
 Cardiovascular death is either the leading or one of the main causes of death in
patients with chronic kidney disease (CKD).
 CKD is one of the main features associated with poor outcomes in cardiovascular
disease patients, especially those with heart failure and/or diabetes.
 The most suitable choice of components of the composite endpoint for a
cardiovascular outcome trial conducted specifically in the CKD population is
obviously key for success and depends on the specific therapy being tested.
 Renal endpoints are pathophysiologically relevant in a CKD population even if the
primary intervention target is cardiovascular disease, and a composite endpoint
reflecting both cardiovascular and renal outcomes may be desirable, especially if
the intervention is expected to affect both systems.
 However, a challenging problem is which endpoints to combine and how to
interpret the results of the composite endpoint.
 Moreover the meaning of a worsening renal function may be different depending
on the considered setting (acutely decompensated heart failure vs. chronic, renin
angiotensin aldosterone system inhibition (RAASi) use and uptitration, biphasic
temporal effect of SGLT2 inhibition on kidney function…).
 One may also wonder if changes in estimated glomerular filtration rate and/or
microalbuminuria should be considered as relevant biotargets and surrogates of
outcomes whilst assessing the cardiovascular benefit of a new compound and if
any, which outcome (cardiovascular or renal) should be prioritized for testing if
the compound exhibits cardiorenal effects.
 Finally, should we pay attention to a worsening in renal function under RAASi as
long as potassium concentrations are maintained in the normal range with a
potassium binder?
Welcome Remarks
Understanding and overcoming the challenges to involving patients with kidney
disease in cardiovascular trials: KHI Project Overview
Julie Ishida (San Francisco, USA)
· Involving patients with kidney disease in cardiovascular and diabetes trials
Lessons Learned and Future Directions
Charles Herzog (Minneapolis, USA)
· Are surrogate endpoints inevitable?
George Bakris (Chicago, USA)

Changes in GFR: How to assess? Reversible vs. irreversible, short – term vs.
long-term, and when are these good news, neutral news, or bad news?
Claudio Ronco (Vicenza, ITA)
Michael Felker (Durham, USA)
The Issue with competing risk and composite endpoints
Janet Wittes (Washington, USA)
Definitions of 'Worsening Renal Function' in cardiorenal trials. How to balance
sensitivity and specificity?
Patrick Rossignol (Nancy, FRA)
Should renal function ever be a primary efficacy endpoint or only a safety
endpoint in heart failure?
· Cardiologist viewpoint
Faiez Zannad (Nancy, FRA)
· Nephrologist viewpoint
Rajiv Agarwal (Indianapolis, USA)
Renal endpoints in the setting of CV prevention trials
· Hypertension
George Bakris (Chicago, USA)
· Diabetes Kidney Disease
o FIGARO – FIDELIO
Rajiv Agarwal (Indianapolis, USA)
o CREDENCE
Vlado Perkovic (Sydney, AUS)
· Regulatory viewpoint:
Angeles Alonso (EMA, GBR), Aliza Thompson (FDA, USA);
· Industry and CRO perspective:
Richard Nkulikiyinka (Bayer, GER); Barbara Gillespie (Covance, USA), Alain
Romero (Relypsa, USA); Jula Inrig (Quintiles, USA); Erica Caveney (Quintiles, USA)
· Patients’ perspective:
Cynthia Chauhan (Wichita, USA)

THE FORUM
Moderated discussion with the audience
Chairpersons: Prabir Roy- Chaudhury (Tucson, USA); Patrick Rossignol (Nancy, FRA)
Panelists: Rajiv Agarwal (Indianapolis, USA), Angeles Alonso (EMA, GBR), George
Bakris (Chicago, USA), Erica Caveney (Quintiles, USA), Cynthia Chauhan (Wichita,
USA), Michael Felker (Durham, USA), Barbara Gillespie (Covance, USA),
Charles Herzog (Minneapolis, USA), Jula Inrig (Quintiles, USA); Julie Ishida (San
Francisco, USA), Richard Nkulikiyinka (Bayer, GER), Vlado Perkovic (Sydney, AUS),
Alain Romero (Relypsa, USA), Claudio Ronco (Vicenza, ITA), Patrick Rossignol (Nancy,
FRA), Prabir Roy-Chaudhury (Tucson, USA), Aliza Thompson (FDA, USA); Janet Wittes
(Washington, USA), Faiez Zannad (Nancy, FRA)

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Nov
30
9:30 AM09:30

ONGOING AND FUTURE ATHEROSCLEROSIS TRIALS

Chairpersons: Wolfgang Koenig (Munich, GER), Jean Claude Tardif (Montreal, CAN)
9.30 am – 12.30 pm / 2.00 pm – 3.30 pm
Residual risk still represents an important issue in patients with manifest cardiovascular
disease despite standard of care treatment. Thus, over 5 years post-ACS still 20% of
patients have experienced a recurrent event.
Several additional strategies have been reported this year or are presently being tested
in large clinical trials like aggressive lowering of LDL cholesterol by PCSK9 inhibition or
an RNA silencing mechanism, lowering of Lp(a) and finally triglycerides (TG) have seen
a revival and their lowering is presently being tested in several trials applying different
interventions like high-dose omega-3 and 6 or a SPARM (selective PPARα modulator).
But novel strategies are at the horizon.
The recently published FOURIER Study has shown a 20% decrease of a combined
endpoint consisting of cardiovascular death, MI and stroke in stable patients with
manifest atherosclerosis and an index event that had occurred 3 years before
randomization. These results fit very nicely in the cholesterol trialists estimation.
However, despite having reached on treatment LDL-C levels of 30 mg/dl there was a
significant number of patients with recurrent events, which is in line with 36% of patients
showing progression in the previously published GLAGOV IVUS Trial also with
evolocumab. Thus, there is room for other pathomechanisms and anti-inflammatory
treatment on top of standard of care might represent a further option. During ESC this
year results of the CANTOS trial in which 10,000 post MI patients were treated with an
interleukin-1β antagonist have been presented, showing a positive outcome with a
similar effect size on major cardiovascular endpoints as seen during potent LDL-C
lowering with a PCSK9 inhibitor. Thus, this implicates proof of the “inflammation
hypothesis” and a paradigm change in the treatment of patients with manifest
atherosclerosis. This may enable a personalized approach to treatment identifying those
with “residual cholesterol risk” versus those with “residual inflammatory risk”.
PCSK9 Trials
· PCSK9: From discovery to clinical evidence
Marianne Abi-Fadel (Beirut, LEB)
· FOURIER: enough evidence to justify widespread use? Did it fulfill its
expectations?
Marc Sabatine (Boston, USA)

Trials of agents targeting inflammation
· CANTOS: Anti-inflammatory treatment in the context of extreme low LDL
levels. Is there still room for improvement?
Paul Ridker (Boston, USA)
· Lessons from COLCOT and other ongoing and future anti-inflammatory
trials
Jean Claude Tardif (Montreal, CAN)
Further insights regarding into triglycerides as a target for intervention:
· Ongoing clinical trials: STRENGTH and PROMINENT
Aruna Pradhan (Boston, USA)
· Targeting triglycerides: Is angiopoietin-like 4 (ANGPLT 4) a new target?
Insights from genomic studies
Heribert Schunkert (Munich, GER)
· Would angiopoietin-like 3 (ANGPLT 3) be the better target?
Sotirios Tsimikas (Ionis Pharmaceutical, USA)
Gaining precision with cardiovascular clinical trials using genomics
Marie-Pierre Dubé (Montréal, CAN)
Percutaneous coronary intervention in stable angina (ORBITA Trial)
Darrel Francis (London, GBR)
Industry viewpoint: Don Black (Dalcore, CAN), Jay Edelberg (Sanofi, FRA), Narimon
Honarpour (Amgen, USA), David Kallend (The Medicine Company, USA), Tom Thuren
(Novartis, CHE),
Regulatory viewpoint: Pieter DeGraeff (EMA, NED), Jim Smith (FDA, USA)
Payers viewpoint: How much PCSK9 inhibition can the health care system afford?
Jakub P. Hlavka (Santa Monica, USA)
Patient viewpoint: Annemieke Lenselink (The Hague Area, NED), Marilyn Mann
(Patient advocate, USA)

12.30 pm – 1.00 pm
Key note lecture
“Can We Abolish Coronary Artery Disease?”
Eugene Braunwald (Boston, USA)
The Forum. Moderated discussion with the audience
Regulatory and reimbursment Challenges
Chairpersons: Wolfgang Koenig (Munich, GER), Jean Claude Tardif (Montreal, CAN)
Panelists: Marianne Abi-Fadel (Beirut, LEB), Don Black (Dalcore, CAN), Eugene
Braunwald (Boston, USA), Pieter DeGraeff (EMA, NED), Marie-Pierre Dubé (Montréal,
CAN), Jay Edelberg (Sanofi, FRA), Darrel Francis (London, GBR), Jakub P. Hlavka
(Santa Monica, USA), Narimon Honarpour (Amgen, USA), Larry Husten (CardioBrief,
USA), David Kallend (The Medicine Company, USA), Wolfgang Koenig (Munich, GER),
Annemieke Lenselink (The Hague Area, NED), Marilyn Mann (Patient advocate, USA),
Aruna Pradhan (Boston, USA), Paul Ridker (Boston, USA), Marc Sabatine (Boston,
USA), Heribert Schunkert (Munich, GER), Jim Smith (FDA, USA), Jean Claude Tardif
(Montreal, CAN), Tom Thuren (Novartis, CHE), Sotirios Tsimikas (Ionis Pharmaceutical,
USA),

 

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Nov
30
9:30 AM09:30

EXPANDING THE INDICATIONS OF NOACs. DISSECTION OF THE COMPASS TRIAL IN PATIENTS WITH CORONARY AND/OR PERIPHERAL ARTERY DISEASE

Chairpersons: Deepak Bhatt (Boston, USA), Tabassome Simon (Paris, France)
9.30 am - 12.30 pm
 Peripheral artery disease (PAD) is considered to be a clinical manifestation of
systemic atherosclerosis. Most patients presenting with peripheral artery disease
are at high risk for myocardial infarction, ischemic stroke, and cardiovascular
death. Concomitant clinical evidence of coronary magnifies this risk.
 Antiplatelet therapy and statins, are the cornerstone of care for the prevention of
atherosclerotic events. However, the level of evidence in favor of aspirin in PAD is
modest and is mainly based on a meta-analysis involving approximately 5000
patients. In two large clinical trials, in patients with asymptomatic atherosclerosis
(which was defined as an abnormal ABI value) aspirin was not superior to
placebo in preventing cardiovascular events.
 In the CAPRIE trial, in a broadly defined stable population of patients with
atherosclerotic disease, including coronary artery disease, peripheral artery
disease, and cerebrovascular disease, clopidogrel was superior to aspirin. Benefit
was driven mainly by the subgroup of patients with PAD. These results from
CAPRIE established clopidogrel as the first therapy for peripheral artery disease
to be approved by the Food and Drug Administration.
 The CHARISMA trial, enrolling similar high-risk population of patients with
atherosclerosis found no significant benefit for clopidogrel over aspirin in the risk
of cardiovascular events in the overall population. However, there was a nonsignificant
trend in the subgroup of patients with PAD. Dual antiplatelet therapy
was associated with an increased risk of bleeding. On the basis of this evidence,
clopidogrel monotherapy has been the preferred therapy to manage the
atherothrombotic risk in patients with peripheral artery disease.
 In patients with symptomatic PAD enrolled in the EUCLID trial, ticagrelor was not
superior to clopidogrel for the reduction of cardiovascular events, and each drug
was associated with similar rates of major bleeding.
 The COMPASS trial randomized 27,402 patients with coronary artery disease or
peripheral artery disease (PAD) to receive the oral anticoagulant rivaroxaban at
2.5 mg twice daily plus aspirin at 100 mg/day, or rivaroxaban 5 mg twice daily
without aspirin, or aspirin 100 mg/day without rivaroxaban. The trial was stopped
prematurely more than a year ahead of its planned March 2018 completion
because, in an interim analysis, the primary end point of MI, stroke, or
cardiovascular death "has reached its pre-specified criteria for superiority."
COMPASS, Design, highlights of major results
Deepak Bhatt (Boston, USA)
Target patient population. To what patient do the COMPASS results apply?
Faiez Zannad (Nancy, FRA)

Stopping prematurely.
· Logistical considerations: Informing investigators, managing data backlog,
IRB considerations, transitioning patients to open label …
Jackie Bosch (Hamilton, CAN)
· Methodological and interpretation considerations. How should it impact the
interpretation, generalization of the results?
Stuart Pocock (London, GBR)
Mechanistic plausibility and potential for a class effect?
Deepak Bhatt (Boston, USA)
Patients with coronary artery disease and heart failure. Perspectives for
COMMANDER-HF trial
Faiez Zannad (Nancy, FRA)
Industry viewpoint
Peter DiBattiste (Janssen, USA); Nancy Cooks Bruns (Bayer, GER), Martin
Unverdorben (Daiichi Sankyo, USA)
Regulatory viewpoint
Kaori Shinagawa (PMDA, JPN), Ellis Unger (FDA, USA), Joseph Emmerich (EMA, FRA)
11.25 – 12.30 The Forum. Moderated discussion with the audience
Revisiting the Aspirin dogma in secondary prevention?
Chairpersons: Deepak Bhatt (Boston, USA), Faiez Zannad (Nancy, FRA)
Panelists: Deepak Bhatt (Boston, USA), Jackie Bosch (Hamilton, CAN), Nancy Cooks
Bruns (Bayer, GER), Peter DiBattiste (Janssen, USA), Joseph Emmerich (EMA, FRA),
Stuart Pocock (London, GBR), Kaori Shinagawa (PMDA, JPN), Tabassome Simon
(Paris, France), Ellis Unger (FDA, USA), Martin Unverdorben (Daiichi Sankyo, USA),
Faiez Zannad (Nancy, FRA)

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