Late-Breaking Science Abstracts and Featured Science Abstracts From the American Heart Association’s Scientific Sessions 2023 and Late-Breaking Abstracts in Resuscitation Science From the Resuscitation Science Symposium 2023
2023; Lippincott Williams & Wilkins; Volume: 148; Issue: 25 Linguagem: Inglês
10.1161/cir.0000000000001200
ISSN1524-4539
AutoresAbraham Michael Lincoff, Kirstine Brown‐Frandsen, Helen M. Colhoun, John Deanfield, Scott S. Emerson, Sille Esbjerg, Søren Hardt‐Lindberg, G. Kees Hovingh, Steven E. Kahn, Robert F. Kushner, Ildiko Lingvay, Tuğçe Kalaycı Oral, Marie Mide Michelsen, Jorge Plutzky, Christoffer W Tornoee, Donna H. Ryan, The SELECT Trial Investigators, Dept of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Business Development, Novo Nordisk A S, Søborg, Denmark, Institute of Genetics and Cancer, Univ of Edinburgh, Edinburgh, United Kingdom, Dept of Clinical Science, Univ College London, London London, United Kingdom, Dept of Biostatistics, Univ of Washington, Seattle, Dept of Biostatistics, Novo Nordisk A S, Søborg, Denmark, Project Management - CKAD, Novo Nordisk A S, Søborg, Denmark, Global Medical Affairs, Novo Nordisk A S, Søborg, Denmark, Dept of Medicine, V. Washington, Seattle, Dept of Medicine and Medical Education, Northwestern Univ, Chicago, Dept of Internal Medicine Endocrinology, UT Southwestern Medical Center at Dallas, Dallas, M.S. EE Dr. Steven H. Voldman B.S. in engineering science, Novo Nordisk A S, Søborg, Denmark, Cardiovascular Medicine Division, Brigham and Womens Hospital, Harvard Medical School, Boston, Obesity, Liver Diseases and Devices, Novo Nordisk A S, Søborg, Denmark, Clinical Research, Pennington Biomedical Research Center, Baton Rouge,
Tópico(s)Adipose Tissue and Metabolism
ResumoHomeCirculationVol. 148, No. 25Late-Breaking Science Abstracts and Featured Science Abstracts From the American Heart Association's Scientific Sessions 2023 and Late-Breaking Abstracts in Resuscitation Science From the Resuscitation Science Symposium 2023 Free AccessAbstractPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessAbstractPDF/EPUBLate-Breaking Science Abstracts and Featured Science Abstracts From the American Heart Association's Scientific Sessions 2023 and Late-Breaking Abstracts in Resuscitation Science From the Resuscitation Science Symposium 2023 Originally published18 Dec 2023https://doi.org/10.1161/CIR.0000000000001200Circulation. 2023;148:e282–e317Late-Breaking Science: Obesity - Novel Therapeutics and Implications for Population Health22962: Semaglutide and Cardiovascular Outcomes in Patients With Overweight or Obesity Who Do Not Have DiabetesAbraham M Lincoff1, Kirstine Brown-Frandsen2, Helen M Colhoun3, John Deanfield4, Scott S Emerson5, Sille Esbjerg6, Søren Hardt-Lindberg7, G. Kees Hovingh8, Steven E Kahn9, Robert F Kushner10, Ildiko Lingvay11, Tugce Kalayci Oral8, Marie M Michelsen12, Jorge Plutzky13, Christoffer W Tornoee14, Donna H Ryan15, The SELECT Trial Investigators; 1Dept of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, 2Business Development, Novo Nordisk A/S, Søborg, Denmark, 3Institute of Genetics and Cancer, Univ of Edinburgh, Edinburgh, United Kingdom, 4Dept of Clinical Science, Univ College London, London, United Kingdom, 5Dept of Biostatistics, Univ of Washington, Seattle, WA, 6Dept of Biostatistics, Novo Nordisk A/S, Søborg, Denmark, 7Project Management - 5 CKAD, Novo Nordisk A/S, Søborg, Denmark, 8Global Medical Affairs, Novo Nordisk A/S, Søborg, Denmark, 9Dept of Medicine, VA Puget Sound Health Care System and Univ of Washington, Seattle, WA, 10Dept of Medicine and Medical Education, Northwestern Univ, Chicago, IL, 11Dept of Internal Medicine/Endocrinology, UT Southwestern Medical Center at Dallas, Dallas, TX, 12Med & Science, Novo Nordisk A/S, Søborg, Denmark, 13Cardiovascular Medicine Division, Brigham and Womens Hospital, Harvard Medical School, Boston, MA, 14Obesity, Liver Diseases and Devices, Novo Nordisk A/S, Søborg, Denmark, 15Clinical Research, Pennington Biomedical Research Center, Baton Rouge, LABackground: Semaglutide, a long-acting agonist of the glucagon-like peptide-1 receptor, is approved for use in people with type 2 diabetes and overweight or obesity. It has been shown to reduce the risk of adverse cardiac events in those with type 2 diabetes. Whether semaglutide can reduce cardiovascular risk associated with overweight and obesity in the absence of diabetes is unknown. Methods: In a multicenter, randomized, double-blind, placebo-controlled event-driven superiority trial, we enrolled 17,604 patients 45 years of age or older with pre-existing cardiovascular disease and a body mass index of 27 kg/m2 or greater, but who did not have diabetes. Patients were randomly assigned to receive once weekly subcutaneous semaglutide 2.4 mg or placebo. The primary cardiovascular efficacy endpoint was any component of the composite of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke in a time-to-first-event analysis. Confirmatory secondary endpoints, assessed in a time-to-first-event analyses and tested in hierarchical order, were death from cardiovascular causes, a heart failure composite of death from cardiovascular causes or hospitalization or urgent medical visit for heart failure, and death from any cause. Supportive secondary endpoints, also assessed in a time-to-first-event analyses but without control for multiplicity, included expanded cardiovascular composite endpoints, individual components of cardiovascular composite endpoints, a composite nephropathy endpoint, progression to diabetes, or progression to prediabetes as diagnosed by glycated hemoglobin levels. Changes from randomization to week 104 in body weight, glycated hemoglobin concentrations, and other cardiovascular risk factors were measured. Results: The trial met its primary objective, with a 20% reduction in the primary endpoint by semaglutide compared with placebo. Details of primary and secondary efficacy endpoints and safety findings will be presented. Conclusions: In patients with pre-existing cardiovascular disease and overweight or obesity, but without diabetes, weekly subcutaneous semaglutide 2.4 mg was superior to placebo in reducing the incidence of major adverse cardiovascular events.Author Disclosures: For author disclosure information, please visit the AHA Scientific Sessions 2023 Online Program Planner and search for the abstract title.Late-Breaking Science: Hot Topics in Management of Coronary Artery Disease/Acute Coronary Syndrome23437: DAPA-MI - A Registry-Based Randomized Trial of Dapagliflozin in Patients With Acute Myocardial Infarction Without DiabetesStefan K James1, David Erlinge2, Robert F Storey3, Darren K McGuire4, Mark de Belder5, Kasper Andersen6, David Austin7, Gabriel Arefalk8, David Carrick9, Robin Hofmann10, Stephen P Hoole11, Daniel A Jones12, Kelvin Lee13, Hans Tygesen14, Peter A Johansson15, Anna Maria Langkilde16, Wilhelm Ridderstråle16, Ehsan Parvaresh Rizi16, John Deanfield17, Jonas Oldgren1; 1Uppsala Clinical Rsch Cntr, Uppsala Univ, Uppsala, Sweden, 2Dept of Cardiology, Lund Univ, Lund, Sweden, 3Cardiovascular Rsch Unit, Univ of Sheffield, Sheffield, United Kingdom, 4Dept of Internal Medicine, UT Southwestern, Dallas, TX, 5NICOR, NHS Arden & GEM Commissioning Support Unit, London, United Kingdom, 6Dept of Med Sciences, Uppsala Univ, Uppsala, Sweden, 7Academic Cardiovascular Unit, The James Cook Univ Hosp, Middlesbrough, United Kingdom, 8Thoracic Cntr, Blekinge Hosp, Karlskrona, Sweden, 9Institute of Cardiovascular and Med Sciences, Univ of Glasgow, Glasgow, United Kingdom, 10Dept of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden, 11Dept of Interventional Cardiology, Royal Papworth Hosp, Cambridge, United Kingdom, 12William Harvey Rsch Institute, Queen Mary Univ of London, London, United Kingdom, 13Lincolnshire Heart Cntr, United Lincolnshire Hosps NHS Trust, Lincoln, United Kingdom, 14Dept of Medicine, South Älvsborg Hosp, Borås, Sweden, 15BioPharmaceuticals Rsch and Development, AstraZeneca, Molndal, Sweden, 16BioPharmaceuticals Rsch and Development, AstraZeneca, Mölndal, Sweden, 17Institute of Cardiovascular Sciences, Univ College London, London, United KingdomBackground: Therapies that could further prevent the development of heart failure (HF) and other cardiovascular (CV) and metabolic events in patients with recent myocardial infarction (MI) represent a large and unmet medical need. Methods: DAPA-MI is a multicenter, parallel-group, registry-based, randomized, double-blind, placebo-controlled phase 3 trial in patients without known diabetes or established chronic HF, presenting with MI and impaired left ventricular systolic function or Q-waves. The primary objective of the trial was to determine, using the win-ratio analytic method, if dapagliflozin 10 mg, given once daily in addition to standard of care therapy, is superior to placebo. The primary outcome was the hierarchical composite outcome of death, hospitalization for HF (HHF), non-fatal MI, atrial fibrillation/flutter, new onset of type 2 diabetes mellitus, HF symptoms as measured by New York Heart Association (NYHA) Functional Classification at last visit, and body weight decrease ≥5% at last visit. Secondary outcomes included time to the first occurrence of HHF or CV death. A registry-based randomized controlled trial (R-RCT) framework allowed for recruitment, randomization, blinding, and pragmatic data collection of baseline demographics, medications, and clinical outcomes using existing national clinical registries (in Sweden and the United Kingdom) integrated with the trial database. Results: The trial enrolled 4017 patients in Sweden and the United Kingdom from December 2020 to March 2023 with a mean age of 63 years. At baseline, approximately 65% had ST-elevation MI, 8% prior MI, and 2% prior stroke. Patients received guideline-directed therapies comprising > 80% use of ACE inhibitors, beta-blockers, statins, and dual antiplatelet therapy. Left ventricular ejection fraction was below 50% in the majority of participants (66%). The outcome results will be available after the deadline of the abstract submission. Conclusions: The DAPA-MI trial was designed to evaluate the effect of dapagliflozin on the incidence of death, HHF, and cardiometabolic outcomes when added to standard of care in patients without diabetes or chronic HF with recent MI and impaired left ventricular systolic function during the index MI hospitalization.Author Disclosures: For author disclosure information, please visit the AHA Scientific Sessions 2023 Online Program Planner and search for the abstract title.21081: Restrictive versus Liberal Blood Transfusion in Patients With Myocardial Infarction and Anemia: Results of the MINT TrialJeffrey L Carson1, Maria M Brooks2, Paul C Hebert3, Shaun G Goodman4, Marnie Bertolet5, P.Gabriel STEG6, Bernard R Chaitman7, Tabassome Simon8, Simone A Glynn9, Renato D Lopes10, Andrew M Goldsweig11, Andrew P Defilippis12, Jinnette D Abbott13, Howard A Cooper14, William J Kostis15, Sunil Rao16, Dean Fergusson17, Harvey D White18, Caroline Alsweiler19, Darrell Triulzi20, Sheryl F Kelsey21, Helaine Noveck1, John H Alexander10, MINT Investigators; 1Medicine, Rutgers Robert Wood Johnson Med, New Brunswick, NJ, 2Epidemiology, Biostatistics and Clinical and Translational Science, Univ of Pittsburgh Sch of Public Health, Pittsburgh, PA, 3Medicine, Univ of Montreal, Montreal, Canada, 4Medicine, St. Michaels Hosp, Toronto, Canada, 5Depts of Epidemiology, Biostatistics, and The Clinical and Translational Science Institute., Univ of Pittsburgh, Pittsburgh, PA, 6Département de Cardiologies, Université Paris-Cité,, Paris, France, 7Medicine, St. Louis Univ, Saint Louis, MO, 8Medicine, APHP.Sorbonne Univ, Paris, France, 9Div of Blood Diseases and Resources, National Heart Lung Blood Insitute, National Institutes of Health, Bethesda, MD, 10Medicine, Duke Clinical Rsch Institute, Duke Univ, Durham, NC, 11Medicine, Baystate Med Cntr, Springfield, MA, 12Vanderbilt Univ Med Cente, Nashville, TN, 13Medicine, Lifespan Cardiovascular Institute, Providence, RI, 14Medicine, Westchester Med Cntr, Valhalla, NY, 15Medicine, Rutgers Robert Wood Johnson Med Sch, New Brunswick, NJ, 16Medicine, NYU Langone Health, New York, NY, 17Medicine, Ottawa Hosp Rsch Insititute, Ottawa, Canada, 18Medicine, Te Toka Tumai, Auckland, New Zealand, 19Medicine, Green Lane Coordinating Cntr, Auckland, New Zealand, 20Pathology, Univ Pittsburgh Sch of Medicine, Pittsburgh, PA, 21Epidemiology, Univ of Pittsburgh Sch of Public Health, Pittsburgh, PABackground: Anemia is common in patients with acute myocardial infarction (MI) and the indications for red blood cell (RBC) transfusion are controversial. Clinical trials suggest that a restrictive transfusion strategy targeting a hemoglobin concentration (Hb) above 7 or 8 g/dL is safe in most clinical settings. However, in patients with MI, the ischemic myocardium is uniquely vulnerable and might benefit from a higher Hb. Methods: MINT is a randomized controlled trial that enrolled patients with ST-segment elevation or non-ST-segment elevation MI consistent with the Third Universal Definition of Myocardial Infarction criteria and anemia. Anemia was defined as a Hb less than 10 g/dL. Participants were randomly allocated to a restrictive or a liberal transfusion strategy. In the liberal transfusion strategy, one unit of RBC's was administered following randomization and enough RBCs were transfused to maintain the Hb at 10 g/dL or above through hospital discharge or 30 days. In the restrictive transfusion strategy, transfusion was permitted, but not required, only when the Hb was less than 8 g/dL (and strongly recommended when the Hb was less than 7 g/dL) or for ischemic symptoms not controlled with medications. Electrocardiogram, Hb and troponin measurements were made within 24 hours prior to randomization and daily for 3 days. Participants were contacted 30 days following randomization to assess vital status and admission to the hospital or emergency room, and at 6 months to assess vital status. Serial cardiac troponin values during the index admission were reviewed for each patient and suspected post-randomization MIs in the first 30 days adjudicated by a Clinical Events Committee blinded to treatment assignment. All prespecified outcomes were identified from hospital records. The primary trial endpoint was the composite of all-cause mortality and MI through 30 days following randomization. Secondary outcomes included the individual components of the primary outcome, and the composite of all-cause mortality, MI, ischemia driven unscheduled coronary revascularization, or readmission to the hospital for an ischemia related cardiac diagnosis within 30 days. Cause of death was classified as cardiac, non-cardiac, or undetermined. Other trial outcomes included heart failure and infection. Results: We have completed enrollment of 3506 patients from 144 sites from the United States, Canada, France, Brazil, New Zealand and Australia, and locked the database in August 2023. The main results will be available for the meeting with the plan for a simultaneous publication in a major journal. Summary: The MINT trial is the largest trial evaluating transfusion thresholds in patients with MI and will provide high quality evidence to guide transfusion decisions taken every day by clinicians in a wide variety of patients with MI and anemia.Author Disclosures: For author disclosure information, please visit the AHA Scientific Sessions 2023 Online Program Planner and search for the abstract title.22178: Percutaneous Coronary Intervention for Stable Angina (ORBITA-2): A Randomised, Placebo-Controlled TrialChristopher Rajkumar1, Michael Foley1, Fiyyaz Ahmed-Jushuf1, Alexandra Nowbar1, Florentina Simader1, Sashiananthan Ganesananthan1, Peter O'Kane2, Peter Haworth3, John Davies4, Tushar Kotecha5, Neil Ruparelia6, Helen Routledge7, nick curzen8, Manas Sinha9, Reto Gamma4, Rupert Williams10, Sukhjinder Nijjer11, Gerald Clesham4, Lal h Mughal7, Jehangir Din12, Tim Kinnaird13, James Spratt10, Sayan Sen11, Ricardo Petraco14, Joban Sehmi15, David J Collier16, Syed Afzal Sohaib17, Thomas Keeble4, Graham Cole1, Frank Harrell18, James Howard1, Matthew Shun-Shin1, Darrel Francis1, RASHA AL-LAMEE1; 1National Heart and Lung Institute, Imperial College London, London, United Kingdom, 2Dept of Cardiology, Univ Hosps Dorset NHS Foundation Trust, London, United Kingdom, 3Dept of Cardiology, Portsmouth Hosps Univ NHS Trust, Portsmouth, United Kingdom, 4Dept of Cardiology, Essex Cardiothoracic Cntr, Basildon, United Kingdom, 5Dept of Cardiology, Royal Free Hosp, London, United Kingdom, 6Dept of Cardiology, Royal Berkshire NHS Foundation Trust, Reading, United Kingdom, 7Dept of Cardiology, Worcestershire Acute Hosps NHS Trust, Worcester, United Kingdom, 8Dept of Cardiology, Univ Hosp Southampton NHS Foundation Trust, Southampton, United Kingdom, 9Dept of Cardiology, Salisbury Hosp NHS Foundation Trust, Salisbury, United Kingdom, 10Dept of Cardiology, St George's Univ Hosps NHS Foundation Trust, London, United Kingdom, 11Dept of Cardiology, Imperial College Healthcare NHS Trust, London, United Kingdom, 12Dept of Cardiology, Univ Hosps Dorset NHS Foundation Trust, Bournemouth, United Kingdom, 13Dept of Cardiology, Cardiff and Vale Univ Health Board, Cardiff, United Kingdom, 14National Heart and Lung Institute, Imperial Colege London, London, United Kingdom, 15Dept of Cardiology, West Hertfordshire Teaching Hosps NHS Trust, Watford, United Kingdom, 16William Harvey Heart Cntr, Queen Mary Univ of London, London, United Kingdom, 17Dept of Cardiology, Barts Health NHS Trust, London, United Kingdom, 18Dept of Biostatistics, Vanderbilt Univ, Nashville, TNIntroduction: The primary role for percutaneous coronary intervention (PCI) in stable coronary artery disease is angina relief. Whilst unblinded trials have shown PCI to be effective, the first placebo-controlled trial, ORBITA, showed no significant improvement in exercise time in patients with single vessel disease with maximal antianginal therapy. ORBITA-2 tests the placebo-controlled efficacy of PCI for angina relief in patients with single and multivessel disease, with minimum tolerated antianginal therapy. Trial Design: ORBITA-2 was a multicentre, double-blind, placebo-controlled trial conducted in the United Kingdom which randomised 301 patients who fulfilled the following inclusion criterion: (i) angina or angina equivalent symptoms (ii) objective evidence of ischaemia, (iii) single or multivessel disease, and (iv) clinical eligibility for PCI. At enrolment, participants completed angina and quality of life questionnaires and antianginal medications were stopped. Angina episodes were documented daily via a dedicated smartphone application, and antianginal medications were introduced as required for intolerable angina according to a pre-specified protocol throughout the trial. At pre-randomisation, angina and quality of life questionnaires were repeated, and treadmill exercise testing and dobutamine stress echocardiography were performed. Participants then underwent coronary angiography including pre-randomisation invasive physiological assessment. Eligible participants were sedated to a deep level of conscious sedation and randomised 1:1 to receive PCI or placebo. Any antianginal medications initiated in the pre-randomisation period were stopped. All participants were discharged on dual antiplatelet therapy. Subjects then entered a 12 week blinded follow up period in which participants and medical and research teams were blinded to treatment allocation. At follow-up, angina and quality of life questionnaires, treadmill exercise testing and dobutamine stress echocardiography were repeated prior to unblinding and return to routine clinical care. Endpoints: The primary endpoint of ORBITA-2 is a daily angina symptom score. This is an ordinal clinical outcome scale of angina health status derived from the number of episodes of angina reported by the patient on a given day, the units of antianginal medication prescribed on that day, and high level category overrides for unblinding due to intolerable angina, acute coronary syndrome and death. Key secondary endpoints are change in Canadian Cardiovascular Society angina class, Seattle Angina Questionnaire, treadmill exercise time and frequency of antianginal initiation and uptitration. Importance: ORBITA-2 will report the placebo-controlled efficacy of PCI in a real-world population of patients with both single and multivessel stable coronary artery disease. ClinicalTrials.gov: NCT03742050Author Disclosures: For author disclosure information, please visit the AHA Scientific Sessions 2023 Online Program Planner and search for the abstract title.Late-Breaking Science: Heart Failure - VADS, Kids, and Money22180: Avoidance of Aspirin With Left Ventricular Assist Devices in Advanced Heart Failure: Primary Results of the International, Double-Blind, Placebo-Controlled ARIES HM3 Clinical TrialMandeep R Mehra, The ARIES Investigators; Cardiovascular Medicine, Brigham and Womens Hosp, Boston, MABackground: Left Ventricular Assist Devices (LVADs) prolong survival and improve quality of life in patients with advanced heart failure. Since advent of LVADs, aspirin has been used on presumption that induced platelet activation requires anti-thrombotic therapy. Prior generation pumps were known to require aspirin due to a greater propensity for stroke or pump thrombosis events, however the fully magnetically levitated HeartMate-3 (HM3) LVAD has demonstrated greater hemocompatibility. Whether aspirin can be safely avoided with the HM3 LVAD or if its use contributes to bleeding events remains unknown. ARIES was designed as an international, double-blind, placebo-controlled study of aspirin in HM3 LVAD treated patients with the hypothesis that withdrawal of aspirin from the antithrombotic regimen will preserve safety and efficacy of the HM3 LVAD and may reduce bleeding complications which confer substantial residual risk. Study Design: We randomized patients 1:1 to either vitamin K antagonist with aspirin (100 mg) or vitamin K antagonist with placebo, with target INR between 2.0-3.0. The primary endpoint for this study will be met if the placebo arm is non-inferior to the aspirin arm in the composite of survival free of any non-surgical (any event occurring >14 days post-implant) major hemocompatibility-related adverse event (stroke, pump thrombosis, bleeding, and arterial peripheral thromboembolism) at 1-year. Secondary endpoints include cumulative hemorrhagic and thrombotic events as well as components of the primary endpoint. Patients were excluded from participation if they required temporary or permanent mechanical circulatory support other than the HM3 LVAD after implant or if they required aspirin for reasons other than the HM3 LVAD. The study required 628 patients to achieve >80% power to prove the hypothesis using a non-inferiority margin of 10% with the Farrington-Manning risk difference approach to non-inferiority at a one-sided alpha=0.025 (accounting for a 30% dropout rate). All patients from the United States have also undergone aspirin response assessment by serum thromboxane B2 testing. Patient Population: A total of 628 Patients were randomized at 49 sites in United States, Canada, United Kingdom, Austria, Czech Republic, Italy, France, Kazakhstan, and Australia. Patients were a median age of 60 years (Q1-Q3 49-68), 31% black, 22.5% Women, 45% INTERMACS profile 3, with most implanted as destination therapy intent (60%). Study Completion: Final Study follow up completes on August 18th,2023, and final analysis will be available by October 6th, 2023. Study Highlight: ARIES is the first international randomized trial to establish an evidence-based benchmark for anti-thrombotic medical therapy with LVADs to reduce residual risk and enroll an ethnically diverse population across heterogenous healthcare paradigms. (NCT04069156, funded by Abbott (Chicago, IL).Author Disclosures: For author disclosure information, please visit the AHA Scientific Sessions 2023 Online Program Planner and search for the abstract title.23364: The TEAMMATE Trial: Everolimus to Prevent Rejection in Children After Cardiac TransplantationChristopher S Almond1, Kevin P Daly2, Erin L Albers3, Juan C Alejos4, Rebecca K Ameduri5, Scott R Auerbach6, Lynsey Barkoff7, Aliessa R Barnes8, Matthew J Bock9, Arene Butto10, Waldemar F Carlo11, Chesney D Castleberry12, Maryanne Chrisant13, Shriprasad R Deshpande14, William Dreyer15, Melanie D Everitt16, Brian D Feingold17, Selena A Gonzales1, Seth A Hollander18, Gloria Klein19, Ashwin K Lal20, Jacqueline Lamour21, JoAnne Lee22, Minmin Lu19, Irene D Lytrivi23, Shelley D Miyamoto24, Elfriede Pahl25, David M Peng26, Ann R Punnoose27, Thomas D Ryan28, Tajinder P Singh29, Jennifer A Su30, David L Sutcliffe31, Steven Zangwill32, Joseph Rossano33, Lynn A Sleeper34; 1Dept of Pediatrics (Cardiology), Stanford Univ, Palo Alto, CA, 2Dept of Pediatrics (Cardiology), Boston Children's Hosp, Boston, MA, 3PEDIATRIC CARDIOLOGY, Seattle Childrens Hosp, Seattle, WA, 4PEDIATRIC CARDIOLOGY, UCLA Mattel Children's Hosp, Los Angeles, CA, 5Pediatric Cardiology, Mayo Clinic, Rochester, MN, 6Dept of Pediatrics (Cardiology), Childrens Hosp Colorado, Aurora, CO, 7Dept of Pediatrics (Cardiology), Stanford, Palo Alto, CA, 8PEDIATRIC CARDIOLOGY, Childrens Mercy Hosp/UMKC, Kansas City, MO, 9Dept of Pediatrics (Cardiology), Rady Children's Hosp, San Diego, CA, 10PEDIATRIC CARDIOLOGY, Children's Healthcare of Atlanta, Atlanta, GA, 11Pediatrics, UAB, Birmingham, AL, 12PEDIATRIC CARDIOLOGY, Pediatric Cardiology Assoc Austin, Austin, TX, 13Pediatric Cardiology, Joe DiMaggio Childrens Hosp, Hollywood, FL, 14PEDIATRIC CARDIOLOGY, Children's National Health System, Washington, DC, 15Pediatric Cardioology, Texas Childrens Hosp, Houston, TX, 16PEDIATRIC CARDIOLOGY, Children's Hosp Colorado, Aurora, CO, 17Pediatrics, UPMC Children's Hosp of Pittsburgh, Pittsburgh, PA, 18Dept of Pediatrics (Cardiology), Stanford Univ Med Ctr, Palo Alto, CA, 19Pediatrics, Boston Children's Hosp, Boston, MA, 20Pediatric Cardiology, U of Utah Primary Children's H, Salt Lake City, UT, 21Pediatric Cardiology, Mount Sinai, new york, NY, 22Dept of Pediatrics (Cardiology), Lucile Packard Children's Hosp Stanford, Palo Alto, CA, 23Pediatric Cardiology, Columbia Univ Med Cntr, Larchmont, NY, 24PEDIATRIC CARDIOLOGY, Childrens Hosp Colorado, Aurora, CO, 25Pediatric Cardiology, Ann and Robert H Lurie Children's Hosp, Wilmette, IL, 26PEDIATRIC CARDIOLOGY, Univ of Michigan, Ann Arbor, MI, 27Pediatric Cardiology, Children's Hosp of Wisconsin, Milwaukee, WI, 28Pediatric Cardiology, Cincinnati Childrens Hosp, Cincinnati, OH, 29Pediatric Cardiology, Boston Childrens Hosp, Waban, MA, 30Pediatric Cardiology, Childrens Hosp of Los Angeles, Los Angeles, CA, 31Pediatric Cardiology, Children's Health Dallas, Dallas, TX, 32Pediatric Cardiology, Phoenix Childrens Hosp, Phoenix, AZ, 33Pediatric Cardiology, Children's Hosp of Philadelphia, Philadelphia, PA, 34Pediatric Cardiology, Boston Children's Hosp, Boston, MABackground: There is controversy whether everolimus, a proliferation signal inhibitor, is safe for preventing rejection after cardiac transplantation because of a higher risk of death due to infection when introduced early after heart transplant. It is unknown whether everolimus is safe and effective when introduced 6 months after heart transplant in children and young adults, a population where FDA-approved immunosuppressants have been lacking. Methods: In this investigator-initiated trial funded by the Department of Defense (DoD), subjects aged 0 to 21 years surviving to 6 months after heart transplant were randomized in a 1:1 ratio to everolimus and low-dose tacrolimus (everolimus group, reflecting the primary immunosuppressant) or standard-dose tacrolimus and mycophenolate mofetil (tacrolimus group) and followed for 30 months. The primary efficacy endpoint was the cumulative burden of biopsy-proven acute cellular rejection, cardiac allograft vasculopathy, and chronic kidney disease (CKD) as measured by the Major Adverse Transplant Event (MATE-3) score, a composite ordinal endpoint capturing prevalence and severity. The primary safety endpoint was the MATE-6 score, which included the MATE-3 events plus 3 additional adverse events: serious infection, post-transplant lymphoproliferative disorder (PTLD), and antibody-mediated rejection. The trial was executed by two coordinating centers (Boston Children's Hospital for data coordination; Stanford/Lucile Packard Children's Hospital for clinical coordination). Results: Between 2018 and 2020, 211 subjects were randomized at 25 US sites where at randomization the mean age was 8.2±6.3 years (17% infants); 46% were female, 40% were non-White or Hispanic; 50% were transplanted for cardiomyopathy; 16% had donor-specific antibodies, and 51% had public health insurance. During the trial, 40% received everolimus as a liquid preparation. Over 30 months of follow-up, 17% of patients had acute rejection, 26% had cardiac allograft vasculopathy, 24% had serious infection, 3% had CKD and 1.4% had PTLD. Five participants (2%) withdrew or were lost to follow-up. The primary and important secondary endpoints will be available at the time of presentation. Conclusion: TEAMMATE is the first multicenter randomized clinical trial in heart transplantation for children and young adults and evaluates the safety and effectiveness of everolimus and low-dose tacrolimus to prevent transplant complications like cardiac allograft vasculopathy, chronic kidney disease, and rejection. The results have the potential to change the standard approach to immunosuppression for children and young adults and lead to FDA approval of the first rejection prophylaxis regimen for pediatric heart transplantation.(Supported by DoD W81XWH-17-1-0532, NCT 03386539)Author Disclosures: For author disclosure information, please visit the AHA Scientific Sessions 2023 Online Program Planner and search for the abstract title.23532: Integrating Cost Into Shared Decision-Making for Heart Failure With Reduced Ejection Fraction: A Trial Providing Out-of-Pocket Costs for Heart Failure Medications During Clinical EncountersNeal W Dickert1, Scott Halpern2, Yi-An Ko3, Dan D Matlock4, Andrea Mitchell5, Sarah Montembeau6, Miranda Moore7, Alanna A Morris8, Birju Rao6, Laura Scherer9, Candace Speight6, Peter Ubel10, Larry A Allen11; 1Dept of Medicine, Div of Cardiology, Emory Univ Sch of Medicine, Atlanta, GA, 2Medicine, Univ of Pennsylvania, Merion Station, PA, 3Biostatistics, Emory Univ Rollins Sch of Public Health, Atlanta, GA, 4Medicine, Univ Colorado, Aurora, CO, 5Medicine, Div of Cardiology, Emory Univ, Atlanta, GA, 6Medicine, Div of Cardiology, Emory Univ Sch of Medicine, Atlanta, GA, 7Family and Preventive Medicine, Emory Univ, Atlanta, GA, 8Medicine, Div of Cardiology, Emory Univ Sch Medicine, Atlanta, GA, 9Medicine, Univ of Colorado Sch of Medicine, Boulder, CO, 10Fuqua Sch of Business, Duke Univ, Durham, NC, 11Medicine, Univ Colorado Denver, Aurora, COBackground: Guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF) can entail high out-of-pocket (OOP) costs, prompting concerns about financial toxicity and access to therapy. Multiple barriers to discussing cost exist. Most directly, OOP medication costs for
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