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National Heart, Lung, and Blood Institute Working Group on Cardiovascular Pharmacogenomics

Executive Summary

The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group on January 7, 2011, at George Washington University (GWU) in Washington, DC to provide recommendations to the NHLBI that would guide informed decisions on research directions and priorities in the field of cardiovascular pharmacogenomics. This meeting was timed to follow the New Frontiers in Personalized Medicine: Cardiovascular Research and Clinical Care conference held the previous day and co-sponsored by the NHLBI, Personalized Medicine Coalition, American College of Cardiology (ACC), American Medical Association, and Cheney Cardiovascular Institute at GWU. The conference brought together leaders from academia, industry, and government to 1) discuss personalized medicine's current and potential impact on cardiovascular patient outcomes; 2) review emerging technologies and applications that may shape the field in the future; 3) discuss the results of an ACC survey examining personalized medicine adoption rates among U.S. cardiologists; 4) identify the barriers to adoption of pharmacogenetics-based personalized medicine in cardiovascular practice; and 5) develop recommendations for next steps with an emphasis on actions and evidence generation that are needed for adoption and improved quality of cardiovascular patient care.

The goals of the NHLBI Working Group were:

  • to review the discussion and recommendations from the New Frontiers in Personalized Medicine: Cardiovascular Research and Clinical Care conference;
  • to identify areas and challenges that should be addressed to further the field of cardiovascular pharmacogenomics and increase its adoption into the clinical setting;
  • to develop recommendations and priorities for implementing current pharmacogenomics-based treatment modalities; and
  • to identify future research needs related to cardiovascular pharmacogenomics.


The Working Group characterized and discussed challenges for cardiovascular pharmacogenomics in five domains: clinical needs, clinical validation, information delivery, education and compliance, and cost-effectiveness:

  • The Working Group sought to identify and prioritize the most pressing clinical needs to focus research and translational efforts.
  • With respect to clinical validation, the Working Group noted the time and cost of conducting large prospective trials with clinical endpoints as outcomes and recognized that it would be difficult to sustain and fund a large number of such trials. At the same time, although retrospective trials can be powerful, they are problematic due to confounding and bias, and any results obtained from these trials should be regarded as preliminary. This highlighted the need to facilitate the collection of DNA and other samples in ongoing and future prospective clinical trials and to encourage the development of innovative clinical trial designs to test pharmacogenomic applications.
  • With respect to information delivery, the Working Group identified barriers to implementation, such as the need for fast delivery of pharmacogenomic data in the point-of-care setting in order to enable clinical decisions, the reliance on clinical workflow rules to streamline a busy clinical schedule, and lack of utilization even when providers are aware that pharmacogenomics may be helpful. Pharmacogenomic guidelines, reference databases, and electronic platforms to integrate personal pharmacogenomic data into the clinical workflow would all be helpful in overcoming these barriers.
  • The Working Group recognized that many of the same barriers and potential solutions are relevant to education and compliance, and that education must be aimed not only at patients but also at providers.
  • Finally, with respect to cost effectiveness, the Working Group recognized that pharmacogenomic testing would add costs that are easy to assess but would also yield clinical benefits and other types of “value” that are harder to quantify. The Working Group noted that there are no established models to use in this relatively new field, requiring the recruitment of expertise to develop such models. These models will be important to persuade various stakeholders to support the implementation of specific pharmacogenomic applications.


The Working Group identified a set of research and policy priorities designed to facilitate the development and adoption of cardiovascular pharmacogenomics in patient care.

High priority research programs and infrastructure needs identified include:

  1. Research projects targeted to high-need areas, including:
    • Small-to-medium size proof-of-concept clinical studies (i.e., several dozen to several hundred participants) to validate preliminary pharmacogenomics findings from basic science studies or post-hoc analyses of clinical trials.
    • Studies to reap the benefit of genome-wide association study (GWAS) locus discovery by identifying causative genes, DNA variants, and biological mechanisms using cellular and organismal model systems, systems biology approaches, integration with bioinformatics databases, targeted candidate gene resequencing, and other methodologies.
    • The development of inexpensive, rapid, and extremely accurate genotyping and targeted resequencing assays for clinical use, acknowledging that current methods are geared towards research applications rather than clinical use.
  2. A training program to develop young investigators with skills in cardiovascular pharmacogenomics. Such a program could include formal training in clinical pharmacology, genetics, biostatistics, informatics, epidemiology, and clinical trial design.
  3. Promote the inclusion and utilization of DNA collections in clinical trials for pharmacogenomics analyses by:
    • Requiring or incentivizing DNA banking for funded clinical trials.
    • Offering storage for sample collections.
    • Providing funding for studies using DNA collections via the ancillary studies program.
  4. Expert panel meetings and/or conferences to:
    • Periodically evaluate the latest evidence for several cardiovascular pharmacogenomics clinical applications and recommend whether to provide funding for large clinical trials. An example of a clinical application that is a high priority for evaluation is the use of CYP2C19 genotypes to guide clopidogrel therapy.
    • Achieve consensus on the optimal use of DNA collections in pharmacogenomics research.
    • Propose innovative clinical trial designs to test pharmacogenomic strategies, acknowledging that large prospective randomized clinical trials will not always be practical or optimal to test many potential pharmacogenomics applications. An example is to compare outcomes between community practice groups that adopt a pharmacogenomics strategy and groups that maintain the usual practices.
    • Achieve consensus on the “best practices” for the use of biostatistics and cost-effectiveness analyses in pharmacogenomic studies.
    • Propose innovative strategies to promote the widespread adoption of pharmacogenomics clinical applications by cardiovascular providers. An example is the use of information technology to educate providers and to integrate pharmacogenomics into the clinical workflow.
  5. Development of a publicly available database, modeled on the Online Mendelian Inheritance in Man database, that would curate functional and pharmacogenomic data as well as evaluate the evidence related to specific DNA variants.
    • The initial focus would be on cardiovascular pharmacogenomics.
    • Subsequent coordination with multiple NIH institutes and centers as well as partners in academia and industry would expand this database across all specialties.
  6. Inclusion of cardiovascular pharmacogenomics experts on guidelines committees to facilitate the inclusion of pharmacogenomics recommendations in clinical guidelines. Such committees include:
    • American College of Cardiology/American Heart Association Task Force on Practice Guidelines (e.g., clopidogrel pharmacogenomics)
    • National Cholesterol Education Program (e.g., statin pharmacogenomics)
    • Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (e.g., beta-blocker pharmacogenomics)

Publication Plans

The Working Group plans to write a detailed summary of the meeting for publication in an appropriate peer-reviewed journal.

Participating Division and Institute

  • Division of Cardiovascular Sciences, NHLBI


  • Dan M. Roden, MD, Vanderbilt University Medical Center

Working Group Members

  • Michael R. Bristow, MD, PhD, University of Colorado Cardiovascular Institute
  • Timothy A. McCaffrey, PhD, George Washington University Medical Center
  • Kiran Musunuru, MD, PhD, MPH, Massachusetts General Hospital
  • Christopher Newton-Cheh, MD, MPH, Massachusetts General Hospital
  • Jay G. Wohlgemuth, MD, Quest Diagnostics Nichols Institute
  • Issam Zineh, PharmD, U.S. Food and Drug Administration


  • Ahmed A.K. Hasan, MD, PhD
  • Dina N. Paltoo, PhD, MPH
  • Yves D. Rosenberg, MD, MPH
  • Karen L. Ulisney, MSN, CRNP
  • Robin Boineau, MD
  • Paula Einhorn, MD

Staff Contact

Last Updated April 2011

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