Late-Breaking Clinical Trial Abstracts
2012; Lippincott Williams & Wilkins; Volume: 126; Issue: 23 Linguagem: Inglês
10.1161/cir.0b013e318278c90d
ISSN1524-4539
Tópico(s)Health Systems, Economic Evaluations, Quality of Life
ResumoHomeCirculationVol. 126, No. 23Late-Breaking Clinical Trial Abstracts Free AccessAbstractPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessAbstractPDF/EPUBLate-Breaking Clinical Trial Abstracts Originally published4 Dec 2012https://doi.org/10.1161/CIR.0b013e318278c90dCirculation. 2012;126:2776–27992012 Late-Breaking Clinical Trial AbstractsLate-Breaking Clinical Trials: Practice Implications for CAD and VTEAspirin for The Prevention of Recurrent Venous Thromboembolism After a First Unprovoked Event: Results of the ASPIRE Randomized Controlled TrialTimothy Brighton1, John Eikelboom2, Kristy Mann3, Rebecca Mister4, Alexander Gallus5, Paul Ockelford6, Harry Gibbs7, Wendy Hague8, Denis Xavier9, Rafael Diaz10, Adrienne Kirby3, John Simes31South Eastern Area Laboratory Services (SEALS), Prince of Wales Hosp, Sydney, Australia 2McMaster Clinic, Hamilton, Canada 3NHMRC Clinical Trials Cntr, Camperdown, Australia 4NHMRC Clinical Trials Cntr, Univ of Sydney, Camperdown, Australia 5Flinders Med Cntr, Adelaide, Australia 6Auckland Hosp, Auckland, New Zealand 7Alfred Hosp, Melbourne, Australia 8NHMRC Clinical Trials Cntr, Sydney, Australia 9St Johns Rsch Institute, Koramangala, India 10Estudios Clínicos Latino America, Rosario, ArgentinaBackground: Patients with a first episode of unprovoked venous thromboembolism (VTE) have a high risk of recurrence once anticoagulant therapy is discontinued. Aspirin may be effective for preventing recurrent VTE in these patients. Methods: 822 patients who had completed 3–24 months of anticoagulant therapy after a first unprovoked VTE were randomized to aspirin, 100 mg daily, or placebo for up to 4 years. The primary outcome was recurrent VTE (symptomatic deep-vein thrombosis (DVT), pulmonary embolism (PE) or fatal PE), & prespecified secondary outcomes were a composite of VTE, MI, stroke and CVD death and a composite for net clinical benefit.* All events were independently adjudicated. Analysis was by intention-to-treat. Results: Mean patient age was 54 years, and 54% were men. The qualifying event was DVT in 57%, PE in 28%, and DVT and PE in 14%. Duration of prior anticoagulation was 6 months in 27%. The median time on study was 40.5 months in the aspirin and 35.9 in the placebo group. By 2 years, an estimated 22% allocated aspirin and 28% on placebo had discontinued study medication. New VTEs occurred in 73 patients on placebo (30 PE) and 57 on aspirin (18 PE), a nonsignificant reduction of 26%. Aspirin significantly reduced the composite outcome, VTE, MI, stroke and CVD death, by 34% (P=0.01) and improved net clinical benefit by 33% (P=0.01), without significantly increasing bleeding. Treatment effects were consistent among important subgroups (all interaction P for trend >0.5). Conclusion: In patients who had completed anticoagulation therapy after a first unprovoked VTE, aspirin was associated with a nonsignificant risk reduction in recurrent VTE. It significantly reduced major thrombotic events and CVD mortality, and significantly improved net clinical benefit. The results substantiate earlier trial evidence and support aspirin being routinely considered for patients with unprovoked VTE for whom anticoagulant therapy has been discontinued.Download figureDownload PowerPointAuthor Disclosures: T. Brighton: Research Grant; Modest; Bayer. J. Eikelboom: Research Grant; Modest; Boehringer Ingelheim. Honoraria; Modest; Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Bayer, Janssen Pharmaceuticals, Daiichi Sankyo. K. Mann: None. R. Mister: None. A. Gallus: Consultant/Advisory Board; Modest; Bayer, Pfizer, Bristol-Myers Squibb, Boehringer-Ingelheim, Astellas, Daiichi-Sankyo. P. Ockelford: Research Grant; Modest; Bayer, Boehringer Ingelheim, Daiichi-Sankyo. Honoraria; Modest; Novo Nordisk, Bayer. Consultant/Advisory Board; Modest; Novo Nordisk, Bayer, Biogen. H. Gibbs: Honoraria; Modest; Covidien, Boehringer Ingelheim, Bayer, AstraZeneca, Sanofi Aventis. Consultant/Advisory Board; Modest; Boehringer Ingelheim, Bayer, Pfizer. W. Hague: None. D. Xavier: Research Grant; Significant; Boehringer Ingelheim, Bristol-Myers Squibb, Cadila Pharma, Sanofi Aventis, GlasoSmithKline, AstraZeneca, Pfizer. R. Diaz: None. A. Kirby: None. J. Simes: Research Grant; Modest; Bayer.Key Words: Venous thrombosis, Antiplatelet drugs, Cardiovascular disease prevention, Clinical trialsA Randomized Trial of Bedside Platelet Function Monitoring to Adjust Antiplatelet Therapy Versus Standard of Care in Patients Undergoing Drug Eluting Stent Implantation: The ARCTIC StudyGilles Montalescot1, Jean-Philippe Collet1, Eric Vicaut2, Guillaume Cayla3, Thomas Cuisset4, Simon Elhadad5, Grégoire Rangé61Pitié-Salpêtrière Univ Hosp, Paris, France 2Hôpital Lariboisière-St. Louis, Paris, France 3CHU Nîmes, Nîmes, France 4Hôpital de la Timone, Marseille, France 5CH de Lagny, Lagny-sur-Marne, France 6CH Louis Pasteur, Le Coudray, FranceBackground: Individual response to oral antiplatelet therapy (APT) is subject to variability and bedside monitoring offers the opportunity of individualizing therapy for stent implantation. Study design: The ARCTIC randomized trial was designed to demonstrate the superiority of a strategy of platelet function monitoring with drug and/or dose adjustments of APT in suboptimal responders as compared to a more conventional strategy without monitoring and without drug and/or dose changes to reduce the primary endpoint evaluated one year after elective drug eluting stent (DES) implantation. We used the VerifyNowTMP2Y12/Aspirin point of care assay for platelet function monitoring on whole blood in the catheterization laboratory just before stent implantation and in the outpatient clinic for maintenance therapy. High on-clopidogrel platelet reactivity was defined by a PRU value >235 and/or a % inhibition 550. In 40 centers, 2,500 patients with stable angina/ischemia or non-ST-elevation ACS undergoing PCI were randomized by IVRS after the coronary angiogram and before stent implantation. When randomized to platelet function monitoring, patients with high on-treatment platelet reactivity had their treatment adjusted in the catheterization laboratory before start of procedure using higher doses of aspirin and/or clopidogrel, prasugrel or GPIIbIIIa inhibitors. Platelet function analyses were repeated 2–4 weeks after PCI for adjustment of maintenance APT using higher or lower MD of aspirin/clopidogrel or switch to prasugrel. The primary end point is the time to first occurrence of all-cause mortality, non-fatal myocardial infarction, definite/probable stent thrombosis, urgent revascularization or non-fatal stroke at 1-year follow-up. Safety end points include major bleedings using different definitions of bleeding. Final results will be presented at the meeting. Conclusion: ARCTIC is the first large scale trial evaluating by randomization the hypothesis of personalized antiplatelet therapy at the time and after DES implantation to improve clinical outcome.Author Disclosures: G. Montalescot: Research Grant; Significant; Abbott Vascular, Asante, AstraZeneca, Biotronik, Boston Scientific, Brahms, Cordis, Daiichi-Sankyo, Eli-Lilly, Fédération Française de Cardiologie, Fondation de France, Indegene, INSERM, Institut de France, Medtronic, Nanospheres, Pfizer, Roche, Sanofi-Aventis, Stentys, SGAM, Société Française de Cardiologie, Thrombosis Research Institute, The Medicines Company. Consultant/Advisory Board; Modest; Atrium, Bayer, BMS, Boehringer-Ingelheim, Choice Pharma, CCS, CHUV, Duke Institute, Europa, EuroRSCG, GLG, GSK, HUG, Iroko, Lead-Up, McKinsey, MSD, Navigant, Novartis, Portola, Royal College Physicians, Springer, TIMI Group, US Zurich, WebMD, Wolters. J. Collet: Research Grant; Significant; BMS, Sanofi-Aventis, Eli Lilly, Guerbet Medical, Medtronic, Boston Scientific, Cordis, Stago, Fondation de France, INSERM, Féderation Française de Cardiologie, Société Française de Cardiologie. Consultant/Advisory Board; Modest; Sanofi-Aventis, Eli Lilly, BMS. Other; Modest; BMS (lecture fees), Sanofi-Aventis (lecture fees), Eli Lilly (lecture fees), AstraZeneca (lecture fees). E. Vicaut: Consultant/Advisory Board; Modest; Abbott, Amgen, Eli Lilly, Pfizer, Sanofi-Aventis, Servier. G. Cayla: Research Grant; Significant; Fédération Française de Cardiologie. Consultant/Advisory Board; Modest; Abbott Vascular, AstraZeneca, CLS Behring, Daiichi Sankyo, Eli Lilly. Other; Modest; Abbott Vascular (lecture fees), AstraZeneca (lecture fees), Biotronik (lecture fees), CLS Behring (lecture fees), Daiichi Sankyo (lecture fees), Eli Lilly (lecture fees), Iroko Cardio (lecture fees). T. Cuisset: Consultant/Advisory Board; Modest; Daiichi Sankyo, Eli Lilly. Other; Modest; AstraZeneca (lecture fees), Abbott Vascular (lecture fees), Biotronik (lecture fees), Boston Scientific (lecture fees), Cordis (lecture fees), Daiichi Sankyo (lecture fees), Edwards Life Sciences (lecture fees), Eli Lilly (lecture fees), Iroko Cardio (lecture fees), Sanofi-Aventis (lecture fees), Servier (lecture fees). S. Elhadad: None. G. Rangé: None.Key Words: Antiplatelet drugs, Percutaneous coronary intervention, Drug eluting stentsFirst Large-Scale Platelet Function Evaluation in an Acute Coronary Syndromes Trial - The TRILOGY ACS Platelet Function Sub-StudyPaul A. Gurbel1, David Erlinge2, E. M. Ohman3, Joseph A. Jakubowski4, Shaun G. Goodman5, Kurt Huber6, Mark Y. Chan7, Jan H. Cornel8, Harvey D. White9, Keith A. Fox10, Dorairaj Prabhakaran11, Paul W. Armstrong12, Udaya S. Tantry13, Matthew T. Roe141Sinai Hosp Cntr for Thrombosis Rsch, Baltimore, MD, 2Skåne Univ Hosp, Lund, Sweden 3Duke Univ Med Cntr, Durham, NC, 4Eli Lilly and Company, Indianapolis, IN, 5St. Michael's Hosp/Univ of Toronto, Toronto, Canada 6Dept of Cardiology, Wilhelminenspital, Vienna, Austria 7National Univ Heart Cntr, National Univ of Singapore, Singapore, Singapore 8Medisch Centrum Alkmaar, Alkmaar, Netherlands 9Green Lane Cardiovascular Service/Auckland City Hosp, Auckland, New Zealand 10Cntr for Cardiovascular Science, Univ of Edinburgh, Edinburgh, United Kingdom 11Cntr for Chronic Disease Control, Vasant Kunj - New Delhi, India 12Candian VIGOUR Cntr - Univ of Alberta, Edmonton, Canada 13Sinai Hosp of Baltimore, Baltimore, MD, 14Duke Clinical Rsch Institute, Durham, NCBackground: The role of platelet function testing for delineating the prognosis of patients with acute coronary syndromes treated with antiplatelet therapy has not been evaluated in a large-scale trial. Methods: TRILOGY ACS is a double-blind, placebo-controlled, randomized trial comparing prasugrel (10 or 5 mg/d) + aspirin vs. clopidogrel (75 mg/d) + aspirin in 9,326 high-risk UA/NSTEMI patients managed medically without revascularization. A 5 mg prasugrel maintenance dose was given for those ≥75 y and/or 85% power to detect a 25% reduction in the primary endpoint for each treatment factor. Results: Baseline characteristics of the study population are presented in Table 1. A total of 55,222 EDTA or placebo infusions were administered. Database lock will take place July 2012. Conclusions: The results of TACT will show whether disodium EDTA chelation or high-dose oral vitamin therapy offer net benefit for patients with coronary disease and a prior MI.Download figureDownload PowerPointAuthor Disclosures: G.A. Lamas: None. R. Boineau: None. C. Goertz: None. D.B. Mark: None. T.C. Rozema: None. R.L. Nahin: None. Y. Rosenberg: None. M. Stylianou: None. J. Drisko: None. K.L. Lee: None.Key Words: Coronary artery disease, Myocardial infarction, Prevention, Pharmacology, VitaminsMain Results of the Future REvascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) TrialValentin Fuster, Michael E. Farkouh Mount Sinai Sch of Medicine, New York, NYBackground: Prior randomized trials suggested that coronary artery bypass grafting (CABG) produced results superior to balloon angioplasty or bare-metal stenting in patients with diabetes. Whether this remains the case in the current era in which drug eluting stents (DESs) are available and routinely used is unknown. FREEDOM is an NHLBI -sponsored, international, randomized controlled trial designed to determine whether CABG or percutaneous coronary intervention (PCI) is the superior approach for revascularization of diabetic patients with multivessel coronary disease (MVD). Methods: In the FREEDOM trial, a total of 1900 diabetic subjects with MVD were randomized to PCI or CABG worldwide from April 2005-March 2010 and followed for a mean of 4.37 years (minimum 2 years). FREEDOM was designed to have 80% power to detect a 27.0% relative reduction in a composite endpoint composed of all-cause mortality, nonfatal myocardial infarction, or stroke (ClinicalTrials.gov number, NCT 00086450). Results: The randomized cohort was 63.1±9.1 years old and 29% female with median diabetes duration 10.2±8.9 years. Results for the primary outcome measure will be available November 2012. Conclusions: The FREEDOM trial definitively determines whether PCI or CABG results in a superior outcome (all cause mortality, myocardial infarction or stroke) in patients with diabetes and multivessel coronary artery disease.Author Disclosures: V. Fuster: None. M.E. Farkouh: Research Grant; Modest; Genentech. Consultant/Advisory Board; Modest; Eli Lilly, Genetech, Sanofi-Aventis, Novartis.Key Words: Coronary artery disease, Percutaneous coronary intervention, AngiogenesisLate-Breaking Clinical Trials: Health Economics and Quality of Life in Contemporary TrialsProspective Evaluation of Outcomes With Stress Perfusion Imaging Versus Stress Wall Motion Imaging During Dobutamine or Exercise EchocardiographyThomas R. Porter, Lynette M. Smith, Feng Xie, Juefei Wu, Deepak Thomas, Stacey L. Therrien, Monique G. Smith, John T. Haas, Eric Williams, Samer Sayyed Univ of Nebraska Med Cntr, Omaha, NEBackground: Retrospective studies examining real-time myocardial contrast echocardiography (RTMCE) during an intravenous (IV) microbubble infusion have improved the detection of coronary artery disease (CAD) during exercise or pharmacologic stress echocardiography (SE). These studies were performed with experienced reviewers in selected patients. The purpose of this study was to prospectively compare the predictive value of RTMCE with conventional stress echo (CSE), where contrast is used only for the Food and Drug Administration indication of left ventricular opacification. Methods: A total of 2063 patients with intermediate pre-test probability undergoing either dobutamine or exercise SE were prospectively randomized to either RTMCE or CSE as their imaging modality during SE. A continuous infusion of Definity (Lantheus Medical) was used for all RTMCE studies to examine for both myocardial perfusion and wall motion, while Definity was used for CSE only when endocardial border delineation was inadequate (46% of all studies). RTMCE was performed with real-time pulse sequence schemes (mechanical index <0.25; frame rate 20–25 Hz). Studies were interpreted immediately by either an experienced reviewer (R1; n=1257) in perfusion imaging, or four Level III reviewers with basic training in perfusion imaging (R2; n=806). Results: Follow-up was available in 2014 patients (median follow up 2.5 yrears). Mean age was 59×13 years (53% women). Patients randomized to RTMCE had slightly lower ejection fraction and higher frequency of prior revascularization (both P<0.005). Abnormal RTMCE studies were more frequent than abnormal CSE (P<0.001), and more frequently abnormal in a multi-vessel territory (P<0.005). Overall event free survival (EFS) in those with positive or negative studies were not different between CSE and RTMCE. The predictive value of a positive study for both CSE and RTMCE was significant for R1 but not for R2 reviewers. Conclusions. Abnormal studies are more frequently detected with RTMCE. ALthough the predictive value of SE with contrast is improved with experienced contrast users, the overall positive or negative predictive value of a dobutamine or exercise SE, when performed with RTMCE versus CSE in general practice, is not different.Author Disclosures: T.R. Porter: Other Research Support; Modest; GE Healthcare, Philips Research North America. Research Grant; Significant; Lantheus Medical Imaging, Astellas Pharma, Philips Healthcare. L.M. Smith: None. F. Xie: None. J. Wu: None. D. Thomas: None. S.L. Therrien: None. M.G. Smith: None. J.T. Haas: None. E. Williams: None. S. Sayyed: None.Key Words: Echocardiography, Contrast echo, EfficacyEconomic Outcomes of Percutaneous Coronary Intervention Performed at Sites With and Without On-Site Cardiac SurgeryEric L. Eisenstein1, Linda Davidson-Ray1, Rex Edwards1, Kevin J. Anstrom1, Patricia A. Cowper1, Daniel B. Mark1, Thomas R. Aversano21Duke Clinical Rsch Institute, Durham, NC, 2Johns Hopkins Med, Baltimore, MDBackground: The Cardiovascular Patient Outcomes Research Team Non-Primary PCI (CPORT-E) trial randomly assigned subjects to undergo percutaneous coronary intervention (PCI) at a hospital without on-site surgery (No-SOS site; n=14,149) or to be transferred to a hospital with on-site surgery for PCI (SOS site; n=4718). No-SOS versus SOS subjects had similar 6-week mortality (0.9% versus 1.0%; P=0.004 for non-inferiority) and 9-month major adverse cardiac event rates (12.1% versus 11.2%; P=0.05 for non-inferiority). While No-SOS versus SOS subjects had fewer staged procedures (26% versus 68%; P<0.001) and catheterization laboratory visits (1.28 versus 1.73; P<.001) during their index PCI; they also had higher rates of any subsequent revascularization at 9 months (8.5% versus 7.0%; P=0.001). Methods: We conducted a prospective economic study to determine whether total medical costs at 9 months were lower for No-SOS versus SOS subjects. Coordinators at CPORT-E sites collected inpatient bills from each subject's index diagnostic catheterization through 9 months follow-up. We estimated medical costs for outpatient cardiac procedures, acute care and observational stays, and emergency department visits using hospital department-specific ratios of cost-to-charge. Physician costs for inpatient care were estimated from care templates with costs assigned using national Medicare reimbursements. Ambulance transportation costs were estimated using site-specific Medicare reimbursements. Economic results are reported as mean values by treatment strategy, with differences in those values, 95% confidence intervals and p-values. Results: Economic results for the entire CPORT-E population will be reported for the index procedure, follow-up period and 9 months cumulative. Economic outcomes include resource use, length of stay, and medical costs for cardiac procedures (diagnostic catheterization, PCI staged and not staged, and coronary artery bypass graft surgery), other hospitalizations (cardiovascular and non-cardiovascular), and emergency department visits. Conclusion: Economic analyses will be completed and full results reported at the November 2012 AHA meeting.Author Disclosures: E.L. Eisenstein: Other Research Support; Significant; Medtronic Endovascular Therapies, Eli Lilly & Company. L. Davidson-Ray: Other Research Support; Significant; AstraZeneca, Eli Lilly & Company. R. Edwards: Other Research Support; Significant; Medtronic Endovascular Therapies. K.J. Anstrom: Research Grant; Significant; AstraZeneca, Eli Lilly and Co., Medtronic Endovascular Therapies, Proctor and Gamble. Consultant/Advisory Board; Modest; Abbott Vascular, AstraZeneca, Bristol-Meyers Squibb, Ikaria. Other; Modest; Pfizer, Vertex. P.A. Cowper: Other Research Support; Significant; Eli Lilly & Company, AstraZeneca, Bristol-Meyers Squibb, Medtronic Endovascular Therapies. D.B. Mark: Research Grant; Significant; AstraZeneca, Gilead, Eli Lilly and Company, Medtronic Endovascular Therapies. Consultant/Advisory Board; Modest; Gilead. T.R. Aversano: Consultant/Advisory Board; Modest; Science First.Key Words: Cost-effectiveness, Percutaneous coronary interventionQuality of Life Outcomes in the Trial to Assess Chelation Therapy (TACT)Daniel B. Mark1, Kevin J. Anstrom2, Robin Boineau3, Christine Goertz4, Theodore C. Rozema5, J. David Knight2, Nancy E. Clapp-Channing2, Diane M. Liu2, Richard L. Nahin6, Yves Rosenberg3, Jeanne Drisko7, Kerry L. Lee2, Gervasio A. Lamas81Duke Univ Med Cntr, Durham, NC, 2Duke Clinical Rsch Institute, Durham, NC, 3National Heart, Lung, & Blood Institute, Bethesda, MD, 4Palmer College of Chiropractic, Davenport, IA, 5Biogenesis Med Cntr, Landrum, SC, 6National Cntr of Complementary and Alternative Medicine, Bethesda, MD, 7Integrative Medicine, the Univ of Kansas Med Cntr, Kansas City, KS, 8Mount Sinai Med Cntr, Miami, FLBackground: The Trial to Assess Chelation Therapy (TACT) is an NIH-funded, randomized, double-blind, placebo-controlled, 2×2 factorial trial comparing 40 infusions of a multicomponent disodium EDTA chelation solution with placebo and oral, high-dose multivitamin and mineral supplement with placebo in post-MI patients. A quality of life (QOL) substudy was conducted to assess patient-reported outcomes. Methods: The TACT QOL battery included the Medical Outcomes Study Short Form-36 (SF-36); the Duke Activity Status Index (DASI); the Seattle Angina Questionnaire (SAQ) Anginal Frequency, Anginal Stability, and Quality of Life subscales; the EQ-5D; a 0–100 health rating; and the Bypass Angioplasty Revascularization Investigation (BARI) work items. QOL data were collected at baseline and at 6, 12, and 24 months post randomization. Results: TACT enrolled 1,708 patients between September 2003 and October 2010, and follow-up QOL data were collected in a randomly selected subset of 911 patients. We collected baseline data on 100% of the QOL subset, with 95% of expected QOL data collected during follow-up. Conclusions: Comparison by intention-to-treat of the QOL endpoints will be presented after the presentation of the TACT clinical results.Download figureDownload PowerPointAuthor Disclosures: D.B. Mark: Research Grant; Significant; Eli Lilly & Company, Gilead, Medtronic, AstraZeneca. Honoraria; Modest; Gilead. K.J. Anstrom: None. R. Boineau: None. C. Goertz: None. T.C. Rozema: None. J. Knight: None. N.E. Clapp-Channing: None. D.M. Liu: None. R.L. Nahin: None. Y. Rosenberg: None. J. Drisko: None. K.L. Lee: None. G.A. Lamas: None.Key Words: Cardiovascular disease, Quality of life, Vitamins, Coronary artery disease, Evidence-based medicineCost-Effectiveness of PCI With Drug Eluting Stents versus Bypass Surgery for Patients With Diabetes and Multi-Vessel Coronary Artery Disease: Results From the FREEDOM TrialElizabeth A. Magnuson1, Valentin Fuster2, Michael Farkouh2, Kaijun Wang1, Katharine Vilain1, Haiyan Li1, Jaime Appelwick1, Victoria Muratov3, Lynn A. Sleeper3, Mouin Abdallah1, David J. Cohen11Saint Luke's Mid America Heart Institute, Kansas City, MO, 2Mount Sinai Sch of Medicine, New York, NY, 3New England Rsch Institutes, Watertown, MABackground: Previous studies have demonstrate
Referência(s)