THURSDAY 3 DECEMBER 2015
BALLROOM
12.00 - 3.00 pm
TRIAL PUBLICATIONS: POINT AND COUNTERPOINT WITH MAJOR JOURNAL EDITORS
 
Moderators: Robert Golub (JAMA, USA); John Jarcho (NEJM, USA); Stuart Spencer (The Lancet, GBR)
  • Over the past several years, a debate has arisen in the academic and research community. Should papers written by researchers be published as open-access? Some suggest papers written by researchers that use public funds should always be made available for free. Others insist that the only way to ensure quality and integrity is to have well respected journals accept only those papers worthy of publication via a peer review process. In some open access journals authors, not readers, pay the price of publication. The existence of this new payment system has encouraged entrepreneurs to set up companies to carry out the intermediate steps, including peer review. Open access has obvious merits but may have a number of limitations..
  • Because randomized controlled trials provide the basis for change in clinical practice, concern that delays in publication of clinical trial results may harm patients, threaten originality, and risk results leaking out in the absence of context has prompted several journals to offer expedited publication for selected submissions. However, there are a number of limitations to fast track, expedited review publication.
  • It has been suggested that the raw data gathered during clinical research, or an abstracted form of the raw data, should be posted at the time of publication of the primary report of the analyses arising from the data, to allow other investigators to confirm the results and to perform other useful analyses (“open data”).
  • Although clinical trials generate vast amounts of data, a large portion is never published or made available to other researchers. A number of stakeholders are clearly pushing for open data, and it is already happening in a limited way. Will it become a rule?
  • Data sharing could advance scientific discovery and improve clinical care by maximizing knowledge production from data collected in trials. In response to public- and private-sector sponsors in the United States and abroad, the Institute of Medicine (IOM) develops guiding principles and a practical framework for the responsible sharing of clinical trial data..
  • Sharing data is in the public interest, but a multi-stakeholder effort is needed to develop a culture, infrastructure, and policies that will foster responsible sharing.
  • The European Medicines Agency has already adopted data sharing policies.
  • A number of big pharmaceutical firms are also already pursuing open access. The website https://clinicalstudydatarequest.com/ provides access to trial data from participating companies including Astellas, Bayer, Boehringer Ingelheim, Eisai, GSK, Lilly, Novartis, Roche, Sanofi, Takeda, UCB and ViiV Healthcare.
 
Is peer review outdated?
Drummond Rennie (San Francisco, USA)
Stuart Spencer (The Lancet, GBR)
   
Fast track publication: advantages and dangers
présentation John Jarcho (NEJM, USA)
présentation Valentin Fuster (JACC, USA)
   
Should publications of trial results be made "open access"?
présentation Zoë Mullan (The Lancet Global Health, GBR)
   
Should trial data be made "open data"? Is this realistic and useful?
- Institute of Medicine
présentation David DeMets (Madison, USA)
   
- Statistician perspective
présentation Janet Wittes (Washington, DC, USA)
   
Investigator/editor viewpoint
Joseph Hill (Circulation, USA)
Patrick O’Malley (JAMA Intern Med, USA)
Filippo Crea (EHJ, ITA)
 
Medical writing, publication ethics viewpoint:
Wendy Gattis-Stough (Expert Medical Communication, USA)
 
Regulatory viewpoint:
présentation Krishna Prasad (EMA, GBR)
 
The Forum: Moderated discussion with the audience
 
Panellists: Filippo Crea (EHJ, ITA); David DeMets (Madison, USA); Valentin Fuster (JACC, USA); Wendy Gattis-Stough (Cary, USA); Robert Golub (JAMA, USA); Joseph Hill (Circulation, USA); John Jarcho (NEJM, USA); Zoë Mullan (The Lancet Global Health, GBR); Gillian Murtagh (Abbott, USA); Christopher O’Connor (Washington, DC, USA); Patrick O’Malley (Vama intern Med, USA); Milton Packer (Dallas, USA); Krishna Prasad (EMA, GBR); Drummond Rennie (San Francisco, USA); Stuart Spencer (The Lancet, GBR); Ken Stein (Boston Scientific, USA); Janet Wittes (Washington, DC, USA)
 
THEATRE
12.00 – 3.00 pm
CARDIORENAL TRIALS: PREVENTION AND MANAGEMENT OF HYPERKALEMIA
American Society of Nephrology – INI-CRCT – CVCT joint session
 
Moderators: Roxana Mehran (New York, USA), Lars Wallentin (Uppsala, SWE)
  • Hyperkalemia, with both ZS9 and patiromer to enter the US and European market, both have several major trials that were recently completed that are the predecessor of a series of acute studies that will encounter ethical challenges of obtaining consent in critically ill vulnerable populations (many of the potential acute hyperkalemia candidates are enrolled in compassionate dialysis programs).
 
What level of K+ is associated with increased CV risk?
présentation Alexandre Mebazaa (Paris, FRA)
   
New potassium binding agents: How do these work? Dose-effect relationship, other electrolyte effects: any concern with carry over, overshoot, rebound and other non K effects?
présentation Robert Toto (Dallas, USA)
   
Importance of Hyperkalemia in the current treatment gap between clinical guidelines and the utilization of Renin-Angiotensin-Aldosterone System Inhibitors: a call to action
présentation Murray Epstein (Miami, USA)
   
Acute and chronic hyperkalemia therapy future trials: unmet needs and newer opportunities for potassium binding agents
 
présentation - At the emergency department and ICU: Alexandre Mebazaa (Paris, FRA)
présentation - In chronic heart failure: Faiez Zannad (Nancy, FRA)
présentation - In chronic kidney disease: Mikhail Kosiborod (Kansas City, USA)
   
Industry perspective: Lance Berman (Relypsa, USA); Henrik Rasmussen (ZS Pharma, USA)
 
présentation Regulatory perspective: Amany El-Gazayerly (EMA, NED); Aliza Thompson (FDA, USA)
   
The Forum: Moderated discussion with the audience
Hyperkalemia therapy future trials
 
Panellists: Lance Berman (Relypsa, USA); Amany El-Gazayerly (EMA, NED); Murray Epstein (Miami, USA); Charles Herzog (Minneapolis, USA); Mikhail Kosiborod (Kansas City, USA); Alexandre Mebazaa (Paris, FRA); Bertram Pitt (Ann Arbor, USA); Henrik Rasmussen (ZS Pharma, USA); Patrick Rossignol (Nancy, FRA); Prabir Roy-Chaudhury (Tucson, USA); Theodore I. Steinman (Boston, USA); Aliza Thompson (FDA, USA); Robert Toto (Dallas, USA); Faiez Zannad (Nancy, FRA)
 
BALLROOM
3.30 pm – 7.00 pm
AUTONOMIC MODULATION DEVICE THERAPY: SHOULD WE RETHINK THE CLINICAL TRIAL STRATEGY?
American Society of Hypertension – CVCT joint session
 
Moderators: Murray Esler (Melbourne, AUS); Wi l l ia m W h ite (Farmington, USA)
  • Several device-based approaches to autonomic nervous system modulation are under investigation for the treatment of resistant hypertension and heart failure. This line of research has evolved from the long-standing recognition that these diseases originate or are worsened by excess sympathetic activity and loss of parasympathetic tone.
  • Drug therapies including beta-blockers, alpha-blockers, and centrally acting antihypertensive drugs can modulate these neurohormonal systems, but they are often insufficient to control blood pressure or are limited by side effects or patient non-adherence.
  • Technological innovations have produced devices capable of modulating the autonomic nervous system, including renal denervation, carotid baroreceptor stimulation, vagal nerve stimulation, and spinal cord stimulation.
  • Proof-of-concept and phase II studies have been completed for many autonomic modulation therapy devices. Pivotal, phase III trials are either ongoing or being planned.
  • In Europe, several autonomic modulation therapy devices have received the Conformité Européenne (CE)mark. United States Food and Drug Administration (FDA) evaluation of these devices is ongoing. The need for adequately powered, randomized, controlled studies with longer follow-up has been noted.
  • Premarket approval (PMA) is the FDA process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices. Class III devices are those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury.
  • Approvability pathways and the requirements for reimbursement are still a matter of debate.
  • This session is the continuation and update of the previous CVCT Forum discussions with panels of primary investigators of several ongoing trials, along with biostatisticians, National Institutes of Health (NIH) scientists, European and United States regulators, and medical device and pharmaceutical industry scientists and payers representatives about the strengths and limitations of current clinical trials, optimal designs for future trials, approvability of new devices, and considerations for integrating these technologies into practice.
 
Autonomic modulation therapy: a critical appraisal of recent and ongoing trials in hypertension, heart failure and arrhythmias - recommendations for future trials
 
présentation Speaker: John Bisognano (Rochester, USA)
Discussant: William White (Farmington, USA)
présentation Discussant: Faiez Zannad (Nancy, FRA)
   
Need for blinding, placebo effects and regression to the mean
Nancy Geller (NHLBI, USA)
   
How can we manage dose-response and dose finding? Is preclinical testing sufficient?
présentation Gaetano De Ferrari (Pavia, ITA)
   
Autonomic modulation readouts for patient selection, dose finding and/or response prediction/monitoring: any simple test?
présentation Murray Esler (Melbourne, AUS)
   
How important are center-related factors in device/procedure clinical trials, i.e. volume of patients and degree of experience with the procedure?
Felix Mahfoud (Hamburg, GER)
   
The challenge of continuous technological innovations: how might the results of the ongoing trials apply to novel/future technologies?
Ken Stein (Boston Scientific, USA)
   
Industry viewpoint:
présentation Steve Ruble (Boston Scientific, USA)
Elizabeth Galle (CVRx, USA)
   
Regulatory viewpoint:
présentation Bram Zuckerman (FDA/CDRH, USA)
   
Rethinking future hypertension trials? Insight from the Systolic Blood Pressure Intervention Trial (SPRINT)
William Cushman (Memphis, USA)
   
Medicare's approach to coverage of clinical trials and evidence development
Tamara Syrek Jensen and Joe Chin (Medicare and Medicaid Services, USA)
   
The Forum: Moderated discussion with the audience
How can we improve the design of device trials?
 
Panellists: John Bisognano (Rochester, USA); Joe Chin (Medicare and Medicaid Services, USA); William Cushman (Memphis, USA); Gaetano De Ferrari (Pavia, ITA); Murray Esler (Melbourne, AUS); Elizabeth Galle (CVRx, USA); Nancy Geller (NHLBI, USA); Felix Mahfoud (Hamburg, GER); Steve Ruble (Boston Scientific, USA); Ken Stein (Boston Scientific, USA); Tamara Syrek Jensen (Medicare and Medicaid Services, USA); William White (Farmington, USA); Faiez Zannad (Nancy, FRA); Bram Zuckerman (FDA/CDRH, USA)
 
THEATRE
3.30 pm – 7.00 pm
CARDIOVASCULAR OUTCOME TRIALS IN CKD PATIENTS
American Society of Nephrology – INI-CRCT – CVCT joint session
 
Moderators: Vlado Perkovic (Sydney, AUS); Prabir Roy-Chaudhury (Tucson, USA)
  • In patients presenting with CV disease, declining renal function has been associated with increased risk for adverse clinical outcomes. In spite of the high risk of adverse events in this population, CKD patients have largely been excluded from or underrepresented in CV randomized controlled trials. This presents a challenging situation for clinicians to make evidence-based medication choices. Important considerations are necessary to balance benefit and the chance for harm.
  • Classical CV risk factors do not have the same significance in CKD patients. Some bear an inverse relationship to CV outcomes, a phenomenon called reverse-epidemiology. Also the significance and predictive value of biomarkers needs to be specifically examined in CKD patients.
  • Causes and modes of the majority of CV deaths differ and are more frequently attributable to sudden cardiac death and arrhythmia, with relatively few from vasculo-occlusive. The definition of heart failure events is challenging in hemodialysis patients.
  • The use of emerging medications that have not been formally studied in patients with CKD is challenging and the extent to which those medications need to be investigated in CKD patients is an important issue to discuss.
  • Inclusion and better representation of patients with CKD in CV outcome randomized clinical trials seem to be necessary to accurately assess the risks and benefits of medications in this population
  • This is currently being remedied. FIGARO, FIDELIO, FINESSE, ALCHEMIST, PHASE, SAPPHIRE are few examples of CV outcome trials specifically conducted in CKD patients.
  • Updating the regulatory guidance and recommendations for the pharmaceutical industry on the design and conduct of pharmacokinetic studies and/or specific CV outcome trials in patients with impaired renal function is another important issue for debate.
 
Unmet need and challenges related to CV outcomes in CKD and dialysis patients: prevalence, epidemiology and the differing significance of biomarkers
présentation Speaker: Daniel Weiner (Boston, USA)
présentation Discussant: James de Lemos (Boston, USA)
   
Running CV therapy trials specifically in patients with significant renal impairment, or including CKD patients in common CV therapy trials? Pros and cons and insight from recent and ongoing trials
présentation Speaker: Patrick Rossignol (Nancy, FRA)
Discussant: Bertram Pitt (Ann Arbor, USA)
   
Cardiovascular endpoints in CKD and hemodialysis trials: are specific event definitions and adjudication needed?
présentation Patrick Rossignol (Nancy, FRA)
   
Basis to date for providing dosing recommendations in this population: strengths and limitations of using of PK data
Raj Madabushi (FDA, USA)
   
Sudden cardiac death in the ESRD population: new opportunities for diagnosis and therapy
Prabir Roy-Chaudhury (Tucson, USA)
   
Recommendations moving forward
 
- Investigator viewpoint:
présentation Charles Herzog (Minneapolis, USA)
- Regulatory viewpoint:
Peter Mol (EMA, NED); Aliza Thompson (FDA, USA)
- Industry viewpoints:
Michael Hanna (BMS, USA); Christina Nowack (Bayer, GER)
 

The Forum: Moderated discussion with the audience
Cardiorenal trials - how to move the field forward?

 
Panellists: Lance Berman (Relypsa, USA); Julio Chirinos (Philadelphia, USA); Murray Epstein (Miami, USA); Michael Hanna (BMS, USA); Charles Herzog (Minneapolis, USA); So-Young Kim (Bayer, GER), James de Lemos (Boston, USA); Raj Madabushi (FDA, USA); Peter Mol (EMA, NED); Christina Nowack (Bayer, GER); Vlado Perkovic (Sydney, AUS); Bertram Pitt (Ann Arbor, USA); Patrick Rossignol (Nancy, FRA); Prabir Roy-Chaudhury (Tucson, USA); Aliza Thompson (FDA, USA); Daniel Weiner (Boston, USA); Faiez Zannad (Nancy, FRA)
 
FRIDAY 4 DECEMBER 2015
BALLROOM

8.00 am – 12.00 noon
DIABETES CV OUTCOME TRIALS
International Society of Cardiovascular Pharmacology – CVCT joint session

 
Moderators: Felipe Martinez (Cordoba, ARG); Marc Pfeffer (Boston, USA)
  • Regulatory guidance allows informing filing of new products supported by interim analysis (e.g. Diabetes or Obesity safety CVOT to demonstrate HR upper CL <1.8). However, to maintain trail integrity for the continuation of the study post approval, this still should be done while keeping the trial team, investigators and patients blinded. Absent of a clear idea of how to bridge these in themselves contradictory objectives, some companies have decided to delay the US filing until the full safety study is finalized (e.g. Sanofi with ELIXA). The FDA recently convened a public input meeting to discuss how to precisely do this risk of interim analyses would be important to discuss.
  • The LIGHT trial designed to study the cardiovascular safety of the weight-loss drug Contrave (Orexigen/Takeda Pharmaceutical), a naltrexone/bupropion combination, has been halted after the sponsor publicly released data through a patent and securities filing without knowledge from the study's clinical-trial leaders. This unfortunate episode highlights the challenge of applying the regulatory guidance.
  • The consistency of evidence generated since the implementation of the FDA guidance on assessing cardiovascular safety of DM drugs raises the question of whether cardiovascular safety outcome studies remain necessary for all new DM drugs. A more tailored approach might now be appropriate, where the need for cardiovascular outcome studies would be determined by regulators for each individual drug based on its mechanism of action, pre-clinical or phase 1-2 data, and the safety database. Only requiring cardiovascular outcome safety trials when there is suspicion or a signal of an adverse effect seems reasonable given the number of recent studies that have demonstrated non-inferiority and the resources and time involved in conducting these large-scale trials.
  • In CV safety trials, the MACE composite trial endpoint capturing mortality and morbidity have substantial room for improvement. Should heart failure events be captured in the primary endpoint? Should components be weighted? How to determine whether to capture first events versus total events (first and recurrent)? Which other components should be considered (e.g. hospitalization-equivalent outpatient visits for HF, etc.)
  • The question arises the guidance should be updated since the several first Diabetes CV safety studies have shown no increase in CV mortality or morbidity. How to readdress the question whether glucose lowering reduces CV M&M (trial options, patient populations, etc.)?
  • Importantly, with EMPA-REC OUTCOME trial, for the first time ever, a type 2 diabetes drug is shown to improve survival and prevent CV outcome in a population of diabetics with established heart disease, suggesting that the way HbA1c is lowered may be important. Additional pharmacological effects may also play a role. The full results of this disruptive trial will be examined in details in this session. Interpretation and consequences on clinical practice and the future of diabetes trials will be discussed..
 
Diabetes CV safety trials: learnings and recommendations - review of SAVOR, EXAMINE, TECOS, and ELIXA
présentation Marc Pfeffer (Boston, USA)
 
The EMPA-REG OUTCOME trial
- Rationale and study design:
Hans Juergen Woerle (Boehringer Ingelheim, GER)
- Survival MACE and heart failure findings:
  Speaker: Uli Broedl (Boehringer Ingelheim, GER)
présentation   Discussant: Faiez Zannad (Nancy, FRA)
- Microvascular findings:
Hans Juergen Woerle (Boehringer Ingelheim, GER)
- Implication for the patients the physicians and the trialists:
présentation Marc Pfeffer (Boston, USA)
   
CV safety trials: Seeing the trees for the forest - are we losing the prospect for CV protection?
présentation John Cleland (London, GBR)
 
General methodological issues with FDA-guided CV safety trials:
présentation Stuart Pocock (London, GBR)
 
Interim analysis during pivotal studies
présentation Speaker: Steven Nissen (Cleveland, USA)
Discussant: Nancy Geller (NHLBI, USA)
 
Use and misuse of on-off treatment analyses
présentation Janet Wittes (Washington, DC, USA)
 
Industry viewpoint:
présentation Mads Engelmann (Novo Nordisk, DEN); Christina Stahre (AstraZeneca, SWE)
 
Regulatory perspective:
présentation Kristina Dunder (EMA, SWE); Norman Stockbridge (FDA, USA)
présentation Jean-Marc Guettier (FDA, USA)
   
The Forum: Moderated discussion with the audience
Diabetes and obesity CV safety trials: how to move the field forward?
 
Panellists: Uli Broedl (Boehringer Ingelheim, GER); Luther Clark (Merck, USA); Kristina Dunder (EMA, SWE); John Cleland (London, GBR); Mads Engelmann (Novo Nordisk, DEN); Nancy Geller (NHLBI, USA); Jean-Marc Guettier (FDA, USA); Felipe Martinez (Cordoba, ARG); Steven Nissen (Cleveland, USA); Marc Pfeffer (Boston, USA); Stuart Pocock (London, GBR); Jeffrey S Riesmeyer (Lilly, USA); James Smith (FDA, USA); Christina Stahre (AstraZeneca, SWE); Norman Stockbridge (FDA, USA); Colette Strnadova (Health Canada, CAN); Janet Wittes (Washington, DC, USA); Hans-Juergen Woerle (Boehringer Ingelheim, GER); Faiez Zannad (Nancy, FRA)
 
THEATRE

8.00 am – 12.00 noon
THE TRIAL ROADMAP FOR RISK GUIDED ICD THERAPY
Heart Rhythm Society – CVCT joint session

 
Moderators: Jeffrey Goldberger (Chicago, USA); Milton Packer (Dallas, USA)
  • ICD therapy has proven effective in preventing sudden cardiac death (SCD) in patients with low EF and a variety. However, within the patients with an impaired LVEF patients can be identified who may not benefit from an ICD implantation.
  • On another hand, other populations have high risk of SCD independently from LVEF, and are yet to be identified by risk markers.
  • In addition, ICD implant and care is not affordable in many regions.
  • Remote monitoring of implanted devices may provide novel data for better understanding the factors promoting ectopy and for assessing arrhythmia burden. How do we best utilize remote monitoring?
  • Optimizing risk stratification and appropriately triaging individual patients to these invasive options to improve clinical outcomes remains a clinical challenge.
  • Markers of autonomic tone, cardiac repolarization, LV remodeling, fibrosis and scarring are candidates for a better discrimination of patients at risk versus not at risk of SCD.
  • Risk prediction is primarily based on well-conducted prospective observational studies. However, few actionable markers have been validated so far.
  • Certain populations such as patients with CKD, diabetes or LVH/preserved EF may have different risk bioprofiles and should be analyzed separately in risk prediction studies.
  • The most robust evidence for a direct impact of a test on overall health derives from a properly designed randomized comparative clinical study showing meaningful benefit for patient outcomes from test-guided care compared to usual care.
 
The roadmap for risk guided ICD therapy
Jeffrey Goldberger (Chicago, USA)
 
Risk-guided strategy trials
- Omics based risk stratification. PROSE-ICD:
présentation Gordon Tomaselli (Baltimore, USA)
- Abnormal repolarization alternans (TWA), impaired heart rate turbulence (HRT)
  REFINE-ICD: Derek Exner (Calgary, CAN)
présentation   PREDICTION: Johannes Brachmann (Coburg, GER)
 
- MIBG Adreview imaging: ADMIRE-ICD
présentation Faiez Zannad (Nancy, FRA)
 
Ongoing observational risk prediction studies
  Genetics, biomarkers and MRI imaging: pre-DETERMINE:
présentation Christine Albert (Boston, USA)
   
  Using remote monitoring data from implanted devices:
présentation David Slotwiner (New York, USA))
   
Other risk categories eligible for ICD trials
- Diabetes post MI patients. MADIT-SICD: Valentina Kutyifa (Rochester, USA)
présentation - Post MI preserved EF: Konstantinos Gatzoulis (Athens, GRE)
présentation - End stage renal disease: Alfred Buxton (Boston, USA)
   
Industry viewpoint:
présentation Jean-Claude Provost (GE Healthcare, GBR)
Ken Stein (Boston Scientific, USA)
   
Regulatory viewpoint:
Angeles Alonso (EMA, GBR)
présentation Mitchell Shein (FDA, USA)
   
Medicare's coverage process:
Tamara Syrek Jensen and Joe Chin (Medicare and Medicaid Services, USA)
   
The Forum: Moderated discussion with the audience
How to overcome methodological, design, operational and regulatory challenges for risk-guided ICD therapy?
 
Panellists: Christine Albert (Boston, USA); Angeles Alonso (EMA, GBR); Johannes Brachmann (Coburg, GER); Alfred Buxton (Boston, USA); Joe Chin (Medicare and Medicaid Services, USA); Gaetano De Ferrari (Pavia, ITA); Derek Exner (Calgary, CAN); Konstantinos Gatzoulis (Athens, GRE); Jeffrey Goldberger (Chicago, USA); Valentina Kutyifa (Rochester, USA); Milton Packer (Dallas, USA); Jean-Claude Provost (GE Healthcare, GBR); Mitchell Shein (FDA, USA); David Slotwiner (New York, USA); Ken Stein (Boston Scientific, USA); Tamara Syrek Jensen (Medicare and Medicaid Services, USA) Gordon Tomaselli (Baltimore, USA); Faiez Zannad (Nancy, FRA)
 
12.00 noon - 12.30 pm
KEY NOTE LECTURE
DRUG DEVELOPMENT FOR ORPHAN CARDIOVASCULAR DISEASES:
A VIEW FROM THE INDUSTRY
pr̩sentation Jean Paul Clozel, CEO РActelion Pharmaceutical, CHE
BALLROOM
1.30 pm – 6.00 pm
PHENOTYPING HEART FAILURE – IS PRECISION MEDICINE THE WAY FORWARD?
Heart Failure Society of America – CVCT joint session
 
Moderators: Christopher O’Connor (Washington, DC, USA), Bertram Pitt (Ann Arbor, USA))
  • There are but a few areas in medicine where progress has been as remarkable as that observed with HF therapy over the last three decades. In chronic HF with reduced ejection fraction (HFREF), the cumulative mortality benefit of evidence-based therapy translates to a three-fold decrease in death rate.
  • However, progress has been consistent only for chronic HFREF. In acutely decompensated HF and HF with preserved ejection fraction (HFPEF), despite a reasonable number of trials, none of the therapies tested to date have definitively proven to be effective.
  • So far, driven by a trialists’ approach, clinically actionable classifiers of HF are limited to ejection fraction (EF), i.e. HFREF and HFPEF and chronic and acute HF. Heart rate and LBBB are also classifiers which guide lifesaving therapies, respectively, ivabradine and CRT.
  • A disruptive strategic approach is based on combining knowledge based on underlying mechanisms, hemodynamic, omics and imaging bioprofiling, co-morbidities to define mechanistically relevant and clinically actionable bioprofiles.
  • This session explores the potential of generating new HF classifiers with the ultimate aim of improving patient outcomes using mechanistically targeted therapies.
 
Phenotyping heart failure: helpful new tools for patient selection in trials?
- Phenotyping heart failure:
présentation   Speaker: Michael Felker (Durham, USA)
présentation   Discussant: David Kao (Aurora, USA)
présentation - Diabetes HF phenotype(s): Brian Lindman (St Louis, USA)
   
The pulmonary hypertension phenotypes
présentation Stephan Rosenkranz (Cologne, GER)
 
The right drug for the right patient: how to select mechanistically phenotyped patients for bio-targeted therapies?
LCZ 696 trial program, may change the landscape of future HF trials:
Milton Packer (Dallas, USA)
   
Ivabradine crosses the Atlantic: is this good enough?
présentation Jeffrey Borer (New York, USA)
   
Could finerenone beat eplerenone? Results from ARTS-HF trial and perspectives with FINESSE:
Bertram Pitt (Ann Arbor, USA)
   
Cyclic GMP activators and stimulators (Vericiguat):
présentation Carolyn Lam (Singapore, SGP)
   
Endothelin antagonists and Future design of clinical trials in pulmonary hypertension
présentation Andrew Peacock (Glasgow, GBR)
   
Mitochondrial protectants (Bendavia):
présentation John Cleland (London, GBR)
   
Levosimendan:
présentation Alexandre Mebazaa (Paris, FRA)
   
Cardiac myosin activation:
présentation John Teerlink (San Francisco, USA)
   
How best to design a personalized medicine trial? What can be learnt from oncology trialists?
Richard Simon (NCI, NIH, USA)
   
Are heart failure trial investigators ready for it? Insight from the NHLBI heart failure networks
présentation Monica Shah (NHLBI, USA)
   
Translational science perspective:
présentation Joseph Hill (Dallas, USA)
   
Industry viewpoint:
présentation James Carr (Stealth Peptides, USA)
présentation Fady Malik (Cytokinetics, USA)
   
Regulatory viewpoints:
Angeles Alonso (EMA, GBR), Norman Stockbridge (FDA, USA)
   
The Forum: Moderated discussion with the audience
Rethinking trial design and regulatory pathway to meet the precision medicine agenda in heart
 
Panellists: Kirkwood Adams (Chapel Hill, USA); Angeles Alonso (EMA, GBR); Jeffrey Borer (New York, USA); James Carr (Stealth Peptides, USA); John Cleland (London, GBR); Jean-Paul Clozel (Actelion, CHE); Michael Felker (Durham, USA); Mona Fiuzat (FDA, USA); Karen Hicks (FDA, USA), Joseph Hill (Dallas, USA); James Januzzi (Boston, USA); David Kao (Aurora, USA); Mark Kowala (Lilly, USA); Carolyn Lam (Singapore, SGP); Brian Lindman (St Louis, USA); Olivier Madonna (Quantum Genomics, FRA); Fady Malik (Cytokinetics, USA); Alexandre Mebazaa (Paris, FRA), Gillian Murtagh (Abbott, USA); Christopher O’Connor (Washington, DC, USA); Milton Packer (Dallas, USA); Andrew Peacock (Glasgow, GBR); Ileana Piña (New York, USA), Marc Pfeffer (Boston, USA); Bertram Pitt (Ann Arbor, USA); Lothar Roessig (Bayer, GER), Stephan Rosenkranz (Cologne, GER); Sebastien Roux (Actelion, CHE); Monica Shah (NHLBI, USA); Richard Simon (NCI, NIH, USA); Norman Stockbridge (FDA, USA); John Teerlink (San Francisco, USA); Janet Wittes (Washington, DC, USA); Faiez Zannad (Nancy, FRA)
 
THEATRE

1.30 pm – 6.00 pm
THROMBOSIS TRIALS: NEW FRONTIERS AND SAFETY CHALLENGES

   
Moderators: Ken Borow (Bryn Mawr, USA); Freek Verheugt (Amsterdam, NED)
   
Non-valvular atrial fibrillation and stroke trials: who should be treated?
présentation Elaine Hylek (Boston, USA)
   
How should one decide when to use an anticoagulant, ablation therapy, or a LAA closure device?
présentation David Slotwiner (New York, USA)
   
Should NOAC dose be adjusted on exposure (drug blood level) or pharmacodynamics (coagulation test)?
présentation Paul Reilly (Boehringer Ingelheim, USA)
   
The twist on efficacy vs. safety: going patient specific?
présentation Roxana Mehran (New York, USA)
   
The National Medication Safety, Outcomes and Adherence Program (NMSOAP) study of real world comparative effectiveness of NOACs and Warfarin
Ken Borow (Bryn Mawr, USA)
 
Antidote trials and how will reversal agents impact use of NOACs?
présentation Freek Verheugt (Amsterdam, NED)
   
Regulatory perspective:
- FDA/CDER perspective: Robert Temple (FDA, USA)
présentation - FDA/CDRH perspective: Andrew Farb (FDA, USA)
présentation - EMA perspective: Antonio Gómez-Outes (EMA, ESP)
   
Industry perspective:
présentation Pete DiBattiste (Janssen, USA)
Michele Mercuri (Daiichi Sankyo, USA);
   
The Forum: Moderated discussion with the audience
Benefit/risk issues
 
Panellists: Ken Borow (Bryn Mawr, USA); Joe Chin (Medicare and Medicaid Services, USA); Pete DiBattiste (Janssen, USA); Andrew Farb (FDA, USA); Antonio Gómez-Outes (EMA, ESP); Michael Hanna (BMS, USA); Elaine Hylek (Boston, USA); Cecilia Linde (Stockholm, SWE); Raj Madabushi (FDA, USA); Michele Mercuri (Daiichi Sankyo, USA); Roxana Mehran (New York, USA); Paul Reilly (Boehringer Ingelheim, USA); David Slotwiner (New York, USA); Tamara Syrek Jensen (Medicare and Medicaid Services, USA); Robert Temple (FDA, USA); Freek Verheugt (Amsterdam, NED)
 
SATURDAY 5 DECEMBER 2015
BALLROOM

8.00 am - 12.00 noon
USE IN TRIALS AND IN CLINICAL PRACTICE OF BIOMARKERS AND BIOSENSORS
INI CRCT – GREAT network – CVCT joint session

 
Moderators: Kirkwood Adams (Chapel Hill, USA); Alexandre Mebazaa (Paris, FRA)
  • Natriuretic peptides are useful for diagnosis and prognosis, but novel biomarkers have been described that may assess HF severity and prognosis additively (and sometimes superiorly) to natriuretic peptides. Is a one biomarkerfits- all concept still true in HF?
  • Recent literature assessed novel metabolism pathways for natriuretic peptides (glycosylation, effects of neprilysin), it is however unclear whether this will change our practice.
  • Acute HF trials have been disappointing. Among the reasons of failure is the fact that selecting the right patients in each of the several hundred centers is still difficult. Indeed, assessing the level of congestion and myocardial dysfunction in patients that should be included within few hours after admission is still a challenge. Biomarkers, in addition to clinical signs may help introducing homogeneity in the studied cohort.
  • Novel biomarkers, imaging and biosensor technology data can improve the efficiency and technical success at developing novel drug therapies. Many trials of innovative mechanistically targeted therapies failed probably because they enrolled untargeted patient populations. Novel biomarkers and biosensor data should enable new therapies to target patient segments. Across both patient populations novel biomarkers, imaging and biosensor data may also provide a mechanistic understanding that supports explaining the outcome benefit to the mode of action.
  • This session objective is to assess the assess the utility of biomarkers and novel biosensor monitoring technology into heart failure and atrial fibrillation clinical trials to screen patients, identify likely responders and to increase the mechanistic understanding of efficacy. What is the current and future state of these technologies, what is the clinical value of remote monitoring, what is known and unknown about the utility in clinical trials?
  • An explicit classification system for approval of biological molecules (biomarkers); morphological or functional imaging or physiological sensing with innovative biosensors could be the following: Class 3 would mean you measure what you claim to; Class 2 would add that the biomarker had a known association with clinical outcome; Class 1 would mean you had actually shown its use to improve outcomes..
 
Opportunities and limitations of natriuretic peptides for use in clinical trials
présentation James Januzzi (Boston, USA)
   
Should we change our views on the use of NPs in a world with LCZ696 and DPPIV inhibitors?
présentation - LCZ696, NPs and neprilysin intercations: Nicolas Vodovar (Paris, FRA)
- What NP to measure in patients on LCZ696? Milton Packer (Dallas, USA)
   
Are there alternative biomarkers to NPs to judge of congestion in heart failure?
présentation Etienne Gayat (Paris, FRA)
   
Biomarkers, and biosensor technology and how they may help rethinking clinical trials
présentation - eHealth Heart rhythm monitoring and other Biosensor technologies: Johannes Brachmann (Coburg, GER)
présentation - Biomarkers to improve success in HF trials: Michael Felker (Durham, USA)
   
Methodological challenges in designing precision medicine trials using biomarker-biosensor: what can be learned from oncologists?
Richard Simon (NCI, NIH, USA)
   
How can pharma, imaging, biomarker and device companies synergize? How may regulatory bodies help?
Robert Califf (FDA, USA)
 
Industry perspective:
présentation Gillian Murtagh (Abbott, USA)
présentation Jean-Claude Provost (GE Healthcare, GBR)
Ken Stein (Boston Scientific, USA)
   
Regulatory perspective:
présentation Martin Rose (FDA, USA)
présentation Krishna Prasad (EMA, GBR)
présentation Mitchell Shein (FDA, USA)
   
The Forum: Moderated discussion with the audience
Rethinking the regulatory pathway for biomarkers and biosensor technology
 
Panellists: William Abraham (Columbus, USA); Kirkwood Adams (Chapel Hill, USA); Fernando Aguel (FDA, USA); Johannes Brachmann (Coburg, GER); Julian Braz (Roche Diagnostics, CH); Robert Califf (FDA, USA); Michael Felker (Durham, USA); Etienne Gayat (Paris, FRA); David Guez (Servier, FRA); James Januzzi (Boston, USA); Peter Kowey (Wynnewood, USA); Daniel Krainak (FDA, USA); Carolyn Lam (Singapore, SIN); Lars Lund (Stockholm, SWE); Elizabeth Mansfield (FDA, USA); Alexandre Mebazaa (Paris, FRA); Gillian Murtagh (Abbott, USA); Milton Packer (Dallas, USA); Ileana Pina (FDA, USA); Krishna Prasad (EMA, GBR); Jean-Claude Provost (GE Healthcare, GBR); Howard Rutman (Daiichi Sankyo, USA); Mitchell Shein (FDA/CDRH, USA), Monica Shah (NHLBI, USA); Richard Simon (NCI, NIH, USA); Ken Stein (Boston Scientific, USA); Norman Stockbridge (FDA, USA); Nicolas Vodovar (Paris, FRA); Faiez Zannad (Nancy, FRA)
 
THEATRE

8.00 am - 12.00 noon
LONG-TERM ANTIPLATELET TREATMENT IN CORONARY ARTERY DISEASE
European Association of Clinical Pharmacology and Therapeutics - CVCT joint session

 
Dual antiplatelet treatment for chronic post MI secondary CV prevention: review of the evidence so far and the input from PEGASUS
présentation Tabassome Simon (Paris, FRA)
   
Duration of DAPT post PCI: how to generate further needed evidence?
présentation Patrick Serruys (Rotterdam, NED)
   
Endpoint related issues
 
présentation MACE components vs. bleeding types across the various indications (ACS, post ACS). Freek Verheugt (Amsterdam, NED)
présentation And what if we ask the patients? Patient preferences on which outcome matters the most. Joe Selby (PCORI, USA)
   
Triple therapy in concomitant coronary artery disease and atrial fibrillation – what do we know? What evidence do we need and what future trial strategy?
présentation Roxana Mehran (New York, USA)
   
First PCORNET pragmatic clinical trial to evaluate Aspirin dosing in patients with cardiovascular disease
présentation Adrian Hernandez (Durham, USA)
   
Industry viewpoint:
Tomas Andersson (AstraZeneca, SWE)
 
Regulatory viewpoints:
présentation - FDA/CDER perspective: Martin Rose (FDA, USA)
présentation                Ellis Unger (FDA, USA)
présentation - FDA/CDRH perspective: Andrew Farb (FDA, USA)
présentation - EMA perspective: Antonio Gómez-Outes (EMA, ESP)
   
The Forum: Moderated discussion with the audience
How to better involve patients?
 
Panellists: Angeles Alonso (EMA, GBR); Tomas Andersson (AstraZeneca, SWE); Corine Bernaud (AstraZeneca, GBR); Andrew Farb (FDA, USA); Antonio Gómez-Outes (EMA, ESP); Michael Hanna (BMS, USA); Adrian Hernandez (Durham, USA); Roxana Mehran (New York, USA); Martin Rose (FDA, USA); Joe Selby (PCORI, USA); Patrick Serruys (Rotterdam, NED); Tabassome Simon (Paris, FRA); Freek Verheugt (Amsterdam, NED); Ellis Unger (FDA, USA)
 
12.00 noon - 12.30 pm
KEY NOTE LECTURE
Robert Califf, Deputy Commissioner, Office of Medical Products and Tobacco,
US Food and Drug Administration
BALLROOM
1.30 pm – 6.00 pm
ATRIAL FIBRILLATION PREVENTION AND TREATMENT TRIALS
Heart Rhythm Society – CVCT joint session
 
Moderators: Cecilia Linde (Stockholm, SWE); David Van Wagoner (Cleveland, USA)
  • Analysis of clinical practice guidelines reveals a gap between the need for evidence and its availability and more research is required to support evidence-based recommendations as part of a comprehensive approach to prevention and treatment of AF. Developing an evidence base from which we can adequately predict and prevent AF is an important public health goal.
  • The Heart Rhythm Society recently sought to identify key deficiencies and opportunities in research infrastructure, operations, and methodologies as well as basic research targets and how clinical AF research could be improved in the current health care environment.
  • Catheter ablation is usually undertaken in patients with symptomatic paroxysmal AF that is resistant to at least one antiarrhythmic drug. This practice is supported by the results of multiple single center randomized studies showing a significantly better rhythm outcome after ablation. Most of these studies have included patients already resistant to antiarrhythmic drug treatment with no or minimal organic heart disease, and the follow-up was relatively short.
  • Australian trials have shown a significant impact of structured weight loss programs on AF burden. What is the role of lifestyle interventions in the prevention and management of AF?
  • For patients with either persistent AF or long-standing persistent AF, and, the treatment strategies and the benefit– risk ratio of catheter ablation are less well established.
  • Currently available evidence suggests that occurrence of AF in patients with heart failure (HF), in addition to the risk of thromboembolism, leads to a decline in exercise tolerance, worsened quality of life, increased hospitalization, and in many studies an increase in mortality. Results from ongoing prospective multicenter trials in patient subgroups such as AF in congestive heart failure (e.g. CASTLE-AF, ARC-AF and AMICA) are still pending.
  • RAFT-AF compares the effect of catheter ablation-based atrial fibrillation rhythm control to rate control in patients with heart failure and AF on the composite endpoint of all-cause mortality and hospitalization for heart failure.
  • More generally, there is no evidence so far that successful AF ablation will result in reduced mortality. CABANA is a large prospective worldwide trial is exploring this.
  • Technological innovation is racing at fast speed, and it is expected that some would argue that the results of the ongoing trials may not be generalizable, and may not apply to all centers (center-related factors and learning curve), to all procedures (technology related factors) and to all patients (history of AF and concomitant heart disease…) and to all outcomes (hard, AF recurrence and patient reported outcomes)
 
Aim of this session: Examine and compare the design of recent and ongoing trials and discuss the possible outcomes and future impact on clinical practice.
 
Atrial fibrillation prevention and treatment: clinical trials as part of the research agenda
présentation - At the Heart Rhythm Society: David Van Wagoner (Cleveland, USA)
pr̩sentation - At the ESC РEuropean Heart Rhythm Association: Cecilia Linde (Stockholm, SWE)
   
Targeting the right patient population: are current trials addressing personalized AFib prevention/treatment strategies?
présentation Hugh Calkins (Baltimore, USA)
   
How important are center-related factors in clinical trials of interventional procedures, i.e. volume of patients and degree of experience with the procedure?
présentation Tom Wong (London, GBR)
   
What are clinically meaningful endpoints in AF trials?
- AF burden and the role of novel biosensors in AF trials: Peter Kowey (Wynnewood, USA)
présentation - Patient reported outcomes, symptoms, quality of life: Heather Ross (Phoenix, USA)
   
The challenge of continuous technological innovations: how might the results of the ongoing trials apply to novel ablation technologies?
présentation Kevin Heist (Boston, USA)
   
Industry perspective:
présentation Timothy Meyer (Boston Scientific, USA)
   
Regulatory perspective:
présentation Karsten Bruins Slot (EMA, NOR)
Jun Dong (FDA, USA)
   
The Forum: Moderated discussion with the audience
Preparing for evidence based AF prevention/treatment trials
 
Panellists: Karsten Bruins Slot (EMA, NOR); Hugh Calkins (Baltimore, USA); Jun Dong (FDA, USA), Mark Fellman (FDA, USA), David Gordon (NHLBI, USA); Kevin Heist (Boston, USA); Peter Kowey (Wynnewood, USA); Cecilia Linde (Stockholm, SWE); Timothy Meyer (Boston Scientific, USA); Heather Ross (Phoenix, USA); Martin Unverdorben (Daiichi Sankyo, USA); David Van Wagoner (Cleveland, USA); Tom Wong (London, GBR)
 
THEATRE
1.30 pm – 6.00 pm
ATHEROSCLEROSIS TRIALS
 
Moderators: Wolfgang Koenig (Munich, GER); Jean Claude Tardif (Montreal, CAN)
 
Causes and consequences of the underutilization of high intensity statins in ACS patients
présentation Robert Rosenson (New York, USA)
   
PCSK9 inhibitors: almost all said already? Just waiting for results of outcome trials?
présentation Evan Stein (Cincinnati, USA)
   
Is targeting inflammation still an option in patients on very low LDL cholesterol levels? The inflammation theory of atherosclerosis and ongoing trials (CIRT, CANTOS, COLCOT)
présentation Wolgang Koenig (Munich, GER)
   
Ongoing clinical trials in cardiovascular disease with antisense oligonucleotides: Targeting ApoB-100, ApoCIII, Lp(a), ANGPTL3, FXI and angiotensinogen
présentation Sam Tsimikas (Isis Pharmaceuticals, USA)
   
Would a biomarker risk score help identifying high-risk subjects for randomized clinical trials?
présentation James de Lemos (Boston, USA)
   
Optical coherence tomography: ready for the inclusion in clinical trial?
présentation Evelyn Regar (Rotterdam, NED)
   
Personalized medicine: how far have we come? (DalGENE):
présentation Jean Claude Tardif (Montreal, CAN
   
Pharmacogenomic studies: potentials and limitations:
présentation Klaus Lindpaintner (Newark, USA)
   
Mendelian randomization studies
présentation Lipoprotein and Inflammatory targets Daniel Swerdlow (London, GBR)
   
Industry viewpoint:
Andrew Hamer (AMGEN, USA)
 
Regulatory viewpoint:
présentation Pieter de Graeff (EMA, NED)
   
The Forum: Moderated discussion with the audience
Tailoring mechanistically targeted therapy to targeted patient populations
 
Panellists: Pieter de Graeff (EMA, NED); James de Lemos (Boston, USA); Andrew Hamer (Amgen, USA); Wolfgang Koenig (Munich, GER); Klaus Lindpaintner (Newark, USA); Evelyn Regar (Rotterdam, NED); James Revkin (Pfizer, USA), Robert Rosenson (New York, USA); Evan Stein (Cincinnati, USA);