Author + information
- Received July 8, 2010
- Revision received September 30, 2010
- Accepted October 6, 2010
- Published online January 18, 2011.
- Martin B. Leon⁎ (, )
- Nicolo Piazza,
- Eugenia Nikolsky,
- Eugene H. Blackstone,
- Donald E. Cutlip,
- Arie Pieter Kappetein,
- Mitchell W. Krucoff,
- Michael Mack,
- Roxana Mehran,
- Craig Miller,
- Marie-angéle Morel,
- John Petersen,
- Jeffrey J. Popma,
- Johanna J.M. Takkenberg,
- Alec Vahanian,
- Gerrit-Anne van Es,
- Pascal Vranckx,
- John G. Webb,
- Stephan Windecker and
- Patrick W. Serruys
- ↵⁎Reprint requests and correspondence:
Dr. Martin B. Leon, Columbia University Medical Center, Center for Interventional Vascular Therapy, 173 Fort Washington Avenue, Heart Center, 2nd Floor, New York, New York 10032
Objectives To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health.
Background Transcatheter aortic valve implantation may provide a worthwhile less invasive treatment in many patients with severe aortic stenosis and since its introduction to the medical community in 2002, there has been an explosive growth in procedures. The integration of TAVI into daily clinical practice should be guided by academic activities, which requires a harmonized and structured process for data collection, interpretation, and reporting during well-conducted clinical trials.
Methods and Results The Valve Academic Research Consortium established an independent collaboration between Academic Research organizations and specialty societies (cardiology and cardiac surgery) in the USA and Europe. Two meetings, in San Francisco, California (September 2009) and in Amsterdam, the Netherlands (December 2009), including key physician experts, and representatives from the U.S. Food and Drug Administration (FDA) and device manufacturers, were focused on creating consistent endpoint definitions and consensus recommendations for implementation in TAVI clinical research programs. Important considerations in developing endpoint definitions included: 1) respect for the historical legacy of surgical valve guidelines; 2) identification of pathophysiological mechanisms associated with clinical events; 3) emphasis on clinical relevance. Consensus criteria were developed for the following endpoints: mortality, myocardial infarction, stroke, bleeding, acute kidney injury, vascular complications, and prosthetic valve performance. Composite endpoints for TAVI safety and effectiveness were also recommended.
Conclusions Although consensus criteria will invariably include certain arbitrary features, an organized multidisciplinary process to develop specific definitions for TAVI clinical research should provide consistency across studies that can facilitate the evaluation of this new important catheter-based therapy. The broadly based consensus endpoint definitions described in this document may be useful for regulatory and clinical trial purposes.
The Valve Academic Research Consortium (VARC) consists of representatives from several independent Academic Research Organizations, several Surgery and Cardiology Societies, members of the U.S. Food and Drug Administration, and several independent experts (Appendices 1 and 2). Grants were provided to the ARC Board including representatives of The Cardiovascular Research Foundation, Cardialysis, Duke Clinical Research Institute and Harvard Clinical Research Institute to cover the costs of travel, meeting rooms, and lodging for academic attendees at the San Francisco and Amsterdam meetings by Edwards Lifesciences and Medtronic Corporation. All funds not utilized for the aforementioned travel-related purposes have been returned to the sponsors. Funding was provided by Cardialysis BV on behalf of the Valve Academic Research Consortium. The VARC meetings involved members of the Interventional Cardiology Devices Branch, of the Office of Device Evaluation, Center for Devices and Radiological Health, USFDA. The opinions or assertions herein are the private views of the authors and are not to be construed as reflecting the views of the FDA. This article is copublished in the European Heart Journal.
- Received July 8, 2010.
- Revision received September 30, 2010.
- Accepted October 6, 2010.
- American College of Cardiology Foundation
- Principles for Selecting and Defining Clinical Endpoints for Transcatheter Aortic Valve Implantation Investigations: General Considerations
- Proposed Safety and Efficacy Endpoints
- Prosthetic Valve Performance
- Prosthetic Valve ‘Associated’ Complications
- Clinical Benefit Endpoints
- Therapy-Specific Endpoints
- Clinically Relevant Composite Endpoints
- Appendix 1 Valve Academic Research Consortium Contributing Groups
- Appendix 2 Valve Academic Research Consortium participants
- Appendix 3 Minimum data collection and endpoint requirements after TAVI