STROKE PREVENTION in ATRIAL FIBRILLATION

Transcription

1 QUESTIONS AND TIME CODES The iq&a Interactive Medical Intelligence Zone for STROKE PREVENTION in ATRIAL FIBRILLATION Question # 4 How important is patient convenience when deciding to use a factor Xa or direct thrombin inhibitor for SPAF? Question # 5 What role do you, as an ACS specialist, see for a factor Xa or direct thrombin inhibitor, as part of triple therapy in AF patients who have received a stent? Christopher B. Granger, MD Director Cardiac Care Unit; Co-Director Cardiovascular Clinical Trials Duke University Medical Center Durham, North Carolina Question # 1 What landscape changes should we be focusing on as it relates to SPAF? And how should we interpret the results of new SPAF trials? Individually? And as a group of trials? Question # 2 From a clinical trialist s perspective, how do you suggest we align the RE-LY, AVERROES, and ROCKET-AF trials with specific subsets of patients with AF? Question # 3 Given that intracranial hemorrhage (ICH) is lowered in all the SPAF trials assessing new oral, non-monitored, targeted anticoagulants, how would we approach AF patients on warfarin who appear to be stable with acceptable TTRs? Question # 6 Do results of the ROCKET-AF trial substantiate the concept that patients with higher CHADS 2 risk scores are optimal candidates for rivaroxaban? John Fanikos, RPh Director of Pharmacy Business and Financial Services Brigham and Women s Hospital Adjunct Clinical Professor of Pharmacy Northeastern University Massachusetts College of Pharmacy Question # 7 With respect to SPAF, how will health system pharmacists evaluate costs associated with new oral, non-monitored anticoagulants? Question # 8 How are you evaluating the cost, safety, and efficacy issues of factor X and direct thrombin inhibitors for use in SPAF at your anticoagulation clinic and your institution, in general?

2 Question # 9 Can you give us a primer for how health system pharmacists should evaluate oral factor Xa and direct thrombin inhibitors for their formularies for use in SPAF? Question # 10 How should pharmacy directors conduct and orchestrate the formulary review process for factor Xa and direct thrombin inhibitors? Question # 11 Do you envision that medical-legal issues might come into play when considering replacement of warfarin-based therapy for SPAF with new non-monitored, oral agents targeting factor Xa or thrombin? Richard C. Becker, MD School of Medicine Duke University Director, Duke Cardiovascular Thrombosis Center Duke Clinical Research Institute Durham, North Carolina USA Question # 12 How will cardiovascular specialists use the results of ROCKET-AF and the RE-LY trials to align specific anticoagulants with risk-stratified subsets of AF patients requiring SPAF? Question # 13 Is the preponderance of patients with high-risk CHADS 2 risk scores enrolled in ROCKET-AF sufficiently compelling to support rivaroxaban as a preferred strategy in this patient subgroup? Question # 14 In your view, which AF patients currently on warfarin for stroke prevention should be considered for switching to a direct thrombin or factor Xa inhibitor? Question # 15 What aspects of monitoring new, nonmonitored oral anticoagulants should clinicians be aware of when managing AF patients with these new agents? Question # 16 Based on what we have learned from RE-LY, AVERROES, and ROCKET-AF, what is the role of the CHADS 2 risk assessment tool for identifying optimal anticoagulant choices for SPAF? Question # 17 How should healthcare institutions and cardiovascular specialists evaluate the role of factor Xa and direct thrombin inhibitors as a replacement for warfarin in the setting of SPAF? Question # 18 In an individual patient, how should the clinician make the transition or switch from warfarin to dabigatran or rivaroxaban? And vice versa? Question # 19 How should we transition from warfarin to the new oral anticoagulants in patients undergoing surgical procedures? Question # 20 What is the impact of renal function on dosing of rivaroxaban and dabigatran? Jon Kobashigawa, MD Medical Director, UCLA Heart Transplant Program Co-Chief, Division of Clinical Faculty Medicine Department of Medicine UCLA School of Medicine Los Angeles, California Question # 21 What is the relationship between heart failure (HF) and AF? And what are the implications for SPAF? Question # 22 What is the predictive value of heart failure in conjunction with AF for risk of thrombosis? Risk of stroke? And what is the role of inflammation that accompanies HF?

3 Question # 23 In HF patients with AF, what role will new agents targeting factor Xa or thrombin likely play in patient management? And what might their advantages be in this high-risk population? Question # 24 What is the role of oral anticoagulation in AF patients with systolic versus diastolic heart failure? Question # 25 How should we approach AF in HF patients with respect to rate versus rhythm control? Scott Kaatz, DO Clinical Associate Associate Residency Program Director Department of Medicine Director, Anticoagulation Clinics Henry Ford Hospital Detroit, Michigan Question # 26 Given that the RE-LY, ROCKET-AF, and AVERROES trials for SPAF looked at distinct patient populations with AF, how should we align anticoagulation-based therapies with riskspecific subsets? Is this possible? Question # 27 Since there are significant limitations to making cross-trial comparisons, how do you propose we use available evidence to link new oral anticoagulants with AF subsets? CHADS 2 score? Other clinical features and factors? Question # 28 How should we address the cost issues (and concerns) associated with oral factor Xa and direct thrombin inhibitors? And how do we identify populations most likely to benefit from rivaroxaban, dabigatran, or apixaban? Question # 29 What are the potential medical-legal and/ or ethical risks of not transitioning high-risk patients to new anticoagulants that have been shown to be safer (reduce risk of ICH) and, at the same time, at least non-inferior to warfarin? Question # 30 Why are so many AF patients who are at risk of stroke under-anticoagulated? What drives this failure to prevent stroke syndrome? How can CHADS 2 and guidelines help overcome this problem? David A. Garcia, MD Associate Professor, Division of General Internal Medicine University of New Mexico Co-Director, University of New Mexico Anticoagulation Management Service President, Anticoagulation Forum Albuquerque, New Mexico USA Question # 31 How do we identify and decipher the optimal risk-specific interventions for SPAF based on the results of the ROCKET-AF, RE-LY, and AVERROES trials? Question # 32 Considering the difficulties and pitfalls of making cross-trial comparisons, how should the results of the ROCKET-AF and RE-LY trials, nevertheless, shape our thinking about the role of new agents targeting novel targets for SPAF? Question # 33 Which subsets of AF patients are the best candidates for treatment with new, nonmonitored anticoagulants targeting factor Xa or thrombin? Warfarin stable versus warfarin unstable patients? Role of TTR? Question # 34 How do you envision that formulary decisions will likely be made for these new agents? What factors will you be considering? Question # 35 How does the AVERROES trial offer guidance for warfarin-intolerant or warfarin unsuitable

4 patients with CHADS 2 risk scores that support the need for SPAF? Question # 36 From a practical perspective, when indicated, how should clinicians transition AF patients from warfarin to a direct thrombin inhibitor or factor Xa inhibitor, or vice versa? Question # 37 Will point-of-care, pharmacogenetic testing, and other strategies for improving warfarin therapy and TTR ultimately change the emerging role and need for non-monitored, oral anticoagulants targeting thrombin or factor Xa? Question # 38 How well are we doing getting warfarin therapy to achieve the TTR targets that might make them competitive, from a safety and efficacy perspective, with the new, nonmonitored anticoagulants? Michael D. Ezekowitz, MD Professor and Vice President Lankenau Institute for Medical Research Vice President Clinical Research Main Line Hospitals Wynnewood, Pennsylvania Question # 39 Which AF patients are the best candidates for factor Xa or direct thrombin inhibition in the setting of SPAF? Stable on warfarin? Warfarinnaïve? What are the issues that should be considered? Question # 40 Should factor Xa and direct thrombin inhibitors for SPAF be targeted for warfarin-established or warfarin-naïve patients? For both? How should these choices be made to optimize outcomes? Question # 41 How should cost issues impact our approach to the new factor Xa and direct thrombin inhibitors, and their improved safety and efficacy profiles for SPAF? Jonathan L. Halperin, MD Mount Sinai School of Medicine Director, Clinical Cardiology Service The Zena and Michael A. Wiener Cardiovascular Institute The Marie-Josée and Henry R. Kravis Center for Cardiovascular Health New York, New York Question # 42 What appears to be the clinical and translational implications of the results reported in the ROCKET-AF trial? And how might we compare them to the results of RE-LY and other data? Question # 43 Given the limitations of cross-trial comparisons, what did we learn about the safety and efficacy of rivaroxaban for SPAF in the ROCKET-AF trial? Question # 44 What consistent safety and efficacy findings across the RE-LY, ROCKET-AF, and AVERROES trials are most important from a translational medicine perspective? And which are most likely to reshape the current treatment landscape for SPAF? Question # 45 What, in your view, are the unifying messages that emanate from the SPAF trials evaluating dabigatran, rivaroxaban, and apixaban? Question # 46 Which AF patients, based on the most recent trial results and guidelines, do you consider to be most suitable (or optimal) candidates for treatment with the oral, nonmonitored anticoagulants such as dabigatran, rivaroxaban, or apixaban? Question # 47 Which subsets of AF patients stand to gain

5 the most from such new agents as rivaroxaban or dabigatran? Question # 48 How can clinicians best utilize the CHADS 2 or CHADS 2 -VASC risk stratification scores to optimize risk-directed interventions for SPAF? How can we apply these risk tools to selecting new anticoagulants? Question # 49 What are the important advantages of the CHADS 2 risk assessment tool? And what are its limitations? Question # 50 In the face of new clinical trials such as RE- LY, ROCKET-AF, and AVERROES, are the established AF risk assessment tools still useful for guiding therapy? Peter Libby, MD Chief, Cardiovascular Medicine Brigham and Women s Hospital Mallinckrodt Harvard Medical School Question # 51 Can you articulate the multi-factorial etiology of AF? And what the role of inflammation might be and its intersection with thrombosis? Question # 52 What is the complex relationship among atrial fibrillation, thrombosis, stroke, and the inflammatory state? Question # 53 What is the role of the inflammatory state in white thrombus formation such as that seen in AF? Question # 54 Should anti-inflammatory strategies have a role in managing AF patients at risk from thrombosis and stroke? Question # 55 Why are aggressive antithrombotic strategies for SPAF a critical dimension of cardiovascular care? And what are the pitfalls of warfarin as a foundation agent? Deepak L. Bhatt, MD Chief of Cardiology, VA Boston Healthcare System Director, Integrated Interventional Cardiovascular Program Brigham and Women s Hospital and the VA Boston Healthcare System Senior Investigator, TIMI Group Harvard Medical School Question # 56 How have the recent SPAF trials, including ROCKET-AF, RE-LY, and AVERROES, moved us forward in the sphere of patient management? Has warfarin lost the battle? Question # 57 Which specific patients with AF would you target for the ICH-mitigating effects of rivaroxaban? Dabigatran? Apixaban? Is this safety advantage a bona fide breakthrough? Question # 58 What s your current view about the possible role and safety advantages of oral, non-monitored anticoagulants as part of a triple therapy regimen in AF patients, post-stent, who may require aggressive antithrombotic management? Alexander G.G. Turpie, MD McMaster University Hamilton, Ontario Canada Question # 59 Based on the ROCKET-AF, RE-LY, and AVERROES trials, what is the evidence that

6 directly targeting factor Xa or thrombin can produce superior safety and efficacy (risk reductions) outcomes in the setting of SPAF? Question # 60 Based on the available data from the ROCKET- AF, RE-LY, and AVERROES trials, how should we be using CHADS 2 and/or CHADS 2 -VASC scores to make clinical decisions for SPAF? Question # 61 What perspective will you employ to analyze the cost issues that accompany introduction of factor Xa and direct thrombin inhibitors as a replacement for warfarin in patients requiring SPAF? 81-year-old AF patient who is warfarin-naïve and has a CHADS 2 risk score of 3? What choices and considerations go through your mind? Question # 66 SPAF PATIENT CASE #3 How would you optimize stroke prevention in a 75-year-old AF patient with a TTR of 44% and has CHADS 2 risk score of 3? What choices and considerations go through your mind? Question # 67 SPAF PATIENT CASE #4 How would you optimize stroke prevention in an elderly AF patient who has been in good control on warfarin? What choices and considerations go through your mind? Elaine M. Hylek, MD Associate Department of Medicine Boston University Medical Center Question # 62 How should the focus of the ROCKET-AF trial on high-risk, high-chads 2 risk score patients guide our approach and thinking about selecting oral, non-monitored anticoagulants for SPAF? Question # 63 What are some of the comparative, agentspecific dimensions, including adherence, worth noting among the factor Xa and direct thrombin inhibitors? Question # 64 SPAF PATIENT CASE #1 How would you optimize stroke prevention in a new onset, 65-year-old AF patient who is warfarin-naïve and has a CHADS 2 risk score of 2? What choices and considerations go through your mind? Jeffrey I. Weitz, MD and Biochemistry McMaster University Director, Henderson Research Center Canada Research Chair in Thrombosis Heart and Stroke Foundation J.F. Mustard Chair in Cardiovascular Research Ontario, Canada Question # 68 How do the RE-LY and ROCKET-AF trials, individually, and in aggregate, help shape our thinking about the safety and efficacy advantages of oral, non-monitored anticoagulants targeting factor Xa and thrombin? Question # 69 What is the likely role of factor Xa or direct thrombin inhibitors in AF patients who appear stable, from a TTR perspective, on chronic warfarin therapy? Should we switch to newer agents? Question # 65 SPAF PATIENT CASE #2 How would you optimize stroke prevention in a new onset,

7 Lars Wallentin, MD Professor of Cardiology Uppsala University Uppsala, Sweden Question # 70 What factors might explain the control TTR results in the warfarin arm of the ROCKET-AF trial? Question # 71 What does the RE-LY trial teach us about the relationship between TTR and safety of targeted oral anticoagulants? Question # 72 To optimize safety of SPAF management, what should our approach be for AF patients, with a CHADS 2 risk score of 3, who are on warfarin? How can the TTR help our clinical decision-making? Question # 73 How should the age of a patient affect utilization of oral anticoagulants targeting factor Xa or thrombin in the setting of SPAF? Salim Yusuf, MD Director Population Health Research Institute McMaster University Hamilton, Ontario Question # 74 In the setting of SPAF, who are the best candidates for transitioning patients from warfarin to the new oral anticoagulants? Annabelle Volgman, MD Associate Medical Director Heart Center for Women Rush University Medical College Chicago, Illinois Question # 75 What unique considerations and issues regarding SPAF should we keep in mind for women with AF? Question # 76 What are some of the pitfalls we should be aware of when managing women patients with AF who require anticoagulation for stroke prevention? Question # 77 What is likely to be the role of factor Xa and direct thrombin inhibitors for female patients requiring SPAF? Role of the CHADS 2 and CHADS 2 -VASC scores? Question # 78 What are the looming issues regarding use of these new agents for bridging and in the setting of cardioversion for AF? Question # 79 Which female patients would you identify as optimally suited for switching from warfarin to new, non-monitored oral anticoagulants? Question # 80 What have epidemiological studies about stroke risk in women with AF demonstrated and what are the implications for clinical practice?

8 Samuel Z. Goldhaber, MD Harvard Medical School Director, VTE Research Group Cardiovascular Division Brigham and Women s Hospital President, North American Thrombosis Forum (NATF) Question # 81 Can you give us an overview of the exciting changes that we are witnessing on the landscape of SPAF? And how this iq&a Medical Intelligence Zone will help illuminate and decipher the maze of results, options, and decisions that will challenge the cardiovascular specialist? Question # 82 What challenges and difficult questions are we likely to face as we attempt to translate new data emanating from SPAF trials ROCKET AF, RE-LY, and AVERROES to the front lines of patient care for SPAF? Question # 83 What is the evolving, evidence-based strategy for evaluating and managing patients with newonset, newly diagnosed AF? Question # 84 Given the difficulties of cross-trial analysis, how should we decipher the implications of the maze of pivotal trials those evaluating rivaroxaban, dabigatran, and apixaban focused on pushing the safety and efficacy frontiers of SPAF forward? Question # 85 How can we make cost-effective decisions for SPAF in the setting of newer agents whose acquisition costs are likely to be greater? How can we use cost-modeling to determine optimal, cost-effective care? Question # 86 What are some of the risk- and patient-specific considerations that go into the therapeutic equation for SPAF? And how do we navigate the maze of multiple risk assessment tools and variable clinical needs and patient profiles? Valentin Fuster MD Director, Mount Sinai Heart Director, Zena and Michael Wiener Cardiovascular Institute and the Marie-Josée and Henry R Kravis Center of Cardiovascular Health Question # 87 What are the principle advances in SPAF assessment and management that you anticipate will be translated into the front lines of clinical practice? Question # 88 What is our current thinking about the etiology of AF, and how will this impact our approach to SPAF? Question # 89 What are the most important challenges and barriers to optimizing outcomes in AF? Rate versus rhythm control? Question # 90 How should we align multiple, available and evolving approaches to SPAF with risk-specific subsets of patients with AF? And what is the role of new agents? Question # 91 What advances in risk stratification tools or scoring systems do you think will make the greatest impact in the setting of new trials for SPAF?