The overall objective of this grant proposal is to develop and assess a system to enhance the rational and personalized application of antiplatelet therapy for patients undergoing percutaneous coronary intervention (PCI, or coronary angioplasty and stenting). This proposal describes a 5 year research and training program designed to provide the candidate, Robert Yeh, the necessary skills and experience to develop an independent academic research career in the conduct of translational cardiovascular outcomes research. Candidate: Dr. Yeh received an MSc in health policy from the London School of Economics, an MD from Harvard Medical School, and has completed clinical training in internal medicine (MGH), cardiology (UCSF) and interventional cardiology (MGH). He is now a junior faculty member at the Massachusetts General Hospital with 75% protected time to conduct clinical research. While he has successfully been involved with epidemiologic and secondary data analysis, Dr. Yeh will pursue additional training in the areas of decision analysis, clinical trial conduct and implementation research, and bioinformatics - training which will allow him to translate outcomes research findings into novel interventions which improve patient health. The candidate's long-term goal is to become an R01-funded investigator in the applied outcomes research that has a broad impact on population health. Environment: The candidate will be mentored by Dr. Laura Mauri (Primary Mentor), Associate Professor of Medicine at HMS and chief scientific officer of the Harvard Clinical Research Institute (HCRI), and Dr. Sharon- Lise Normand (Co-Mentor), Professor of Health Care Policy at HMS and Vice Chair of the Patient-Centered Outcomes Research Institute's Methods Committee. Both are internationally recognized leaders in their respective fields, and provide complementary expertise relevant to the research and training of the candidate. Dr. Mauri has an established track record of successfully leading practice-changing multicenter clinical trials in interventional cardiology, including the NIH/FDA/Industry-sponsored Dual Antiplatelet Theray (DAPT) Study. She has mentored several cardiovascular clinical investigators, including those that have received K awards and R01 funding. Dr. Normand has successfully mentored a large number of successful academic investigators, and is an internationally recognized expert in outcomes and comparative effectiveness research methods used in this proposal. The combined resources of several Harvard Medical School institutions, including HCRI, the Department of Health Care Policy, and the MGH Heart Center will support a rich and productive environment for Dr. Yeh's career development through a combination of didactic training, seminars, weekly research meetings, and conference presentations. Research: In the current era of invasive management of coronary artery disease, balancing the tradeoff between ischemic events and bleeding complications has become integral to decisions regarding the type and duration of antiplatelet therapy in patients undergoing coronary intervention.
In Aim 1, multivariable logistic regression will be used to develop models that can predict bleeding and ischemic events in patients after PCI depending on antiplatelet strategy, using data from the DAPT Study, the largest PCI clinical trial conducted to date, and the Massachusetts PCI Registry, a comprehensive longitudinal registry of patients undergoing coronary intervention. Models that can predict treatment benefit or harm associated with specific strategies will be developed.
In Aim 2, decision analysis methods will be employed to enhance these models such that the treatment strategy which is predicted to maximize patient benefit can be identified for all patients, and associated uncertainty in this determination can be assessed.
In Aim 3, these tools will be integrated into a novel software application that can execute multivariable risk predictions at the point of care within the MGH cardiac catheterization laboratory. These tools will be used as clinical decision aids, and tested in a prospective randomized clinical trial to determine whether such interventions can enhance clinical decision making. The research will demonstrate how the end products of outcomes research can be translated into innovative interventions that can """"""""personalize"""""""" medical decisions and ultimately improve patient care.

Public Health Relevance

Stenting of the heart arteries is one of the most commonly performed procedures in the US. Patients who have these procedures are at risk for having both bleeding and clot-related complications during the procedure as well as for months to years afterwards, which require the careful use of antiplatelet medications. This research will develop and assess the impact of tools that can be used by clinicians and patients to help inform the best use of antiplatelet medications after stenting of the heart arteries, such that bleeding and clotting risks associated with these procedures can be minimized for patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL118138-02
Application #
8724553
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Scott, Jane
Project Start
2013-09-01
Project End
2018-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Wasfy, Jason H; Dominici, Francesca; Yeh, Robert W (2016) Letter by Wasfy et al Regarding Article, ""Facility Level Variation in Hospitalization, Mortality, and Costs in the 30 Days After Percutaneous Coronary Intervention: Insights on Short-Term Healthcare Value From the Veterans Affairs Clinical Assessment, Re Circulation 133:e376
Wimmer, Neil J; Secemsky, Eric A; Mauri, Laura et al. (2016) Effectiveness of Arterial Closure Devices for Preventing Complications With Percutaneous Coronary Intervention: An Instrumental Variable Analysis. Circ Cardiovasc Interv 9:e003464
Yeh, Robert W; Secemsky, Eric A; Kereiakes, Dean J et al. (2016) Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention. JAMA 315:1735-49
Karacsonyi, Judit; Karatasakis, Aris; Karmpaliotis, Dimitri et al. (2016) Effect of Previous Failure on Subsequent Procedural Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention (from a Contemporary Multicenter Registry). Am J Cardiol 117:1267-71
Danek, Barbara Anna; Karatasakis, Aris; Karmpaliotis, Dimitri et al. (2016) Use of antegrade dissection re-entry in coronary chronic total occlusion percutaneous coronary intervention in a contemporary multicenter registry. Int J Cardiol 214:428-37
Karmpaliotis, Dimitri; Karatasakis, Aris; Alaswad, Khaldoon et al. (2016) Outcomes With the Use of the Retrograde Approach for Coronary Chronic Total Occlusion Interventions in a Contemporary Multicenter US Registry. Circ Cardiovasc Interv 9:
Mauri, Laura; Elmariah, Sammy; Yeh, Robert W et al. (2016) Causes of late mortality with dual antiplatelet therapy after coronary stents. Eur Heart J 37:378-85
Yeh, Robert W; Mauri, Laura; Wolf, Robert E et al. (2015) Population trends in rates of coronary revascularization. JAMA Intern Med 175:454-6
Yeh, Robert W; Kereiakes, Dean J; Steg, Philippe Gabriel et al. (2015) Benefits and Risks of Extended Duration Dual Antiplatelet Therapy After PCI in Patients With and Without Acute Myocardial Infarction. J Am Coll Cardiol 65:2211-21
Waldo, Stephen W; McCabe, James M; O'Brien, Cashel et al. (2015) Association between public reporting of outcomes with procedural management and mortality for patients with acute myocardial infarction. J Am Coll Cardiol 65:1119-26

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