Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium

Abstract

ObjectivesTo 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.BackgroundTranscatheter 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 resultsThe 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 US 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 (i) respect for the historical legacy of surgical valve guidelines; (ii) identification of pathophysiological mechanisms associated with clinical events; (iii) 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.ConclusionAlthough 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.

Impact of Anesthesia Type on Outcomes of Transcatheter Aortic Valve Implantation (from the Multicenter ADVANCE Study)

“…Death, stroke, myocardial infarction, and reintervention were adjudicated by an independent Clinical Events Committee consisting of TAVI-experienced interventional cardiologists and a cardiac surgeon using the initial Valve Academic Research Consortium definitions. 9 An independent neurologist reviewed the neurological events and provided a summary of each event to the Clinical Events Committee, which used this information along with any other patient source data to adjudicate all neurological events. A core laboratory Comparisons between anesthesia types are based on chi-square or Fisher's exact tests for categorical variables, and t-tests or Wilcoxon tests for continuous variables, as appropriate.…”

1-Year Outcomes After Transcatheter Aortic Valve Replacement With Balloon-Expandable Versus Self-Expandable Valves

“…The devices used int hi sst ud yan dth eT A V Rp r o c e d ur eh av ebe e np r eviously described (12)(13)(14).T h eb a l l o o n -e x p a n d a b l e valve used in this trial (Edwards SAPIEN XT; Edwards Lifesciences, Irvine, California) is a cylindrical cobalt-chromium stent into which 3 leaflets made of bovine pericardium are mounted, whereas the self- STUDY ENDPOINTS. The pre-specified primary endpoint of the CHOICE trial was "device success," as defined by the first Valve Academic Research Consortium (VARC) consensus document (15) and has been previously reported (12).A l lp a t i e n t sw e r e followed-up for at least 1 year and had clinical visits and echocardiographic evaluations at 6 months and 1 year. Pre-specified secondary endpoints included cardiovascular mortality, stroke, repeat hospitalization for heart failure, NewY o r kH e a r tA s STATISTICAL ANALYSIS.…”

Incidence, Predictors and Impact of Severe Periprocedural Bleeding According to VARC-2 Criteria on 1-Year Clinical Outcomes in Patients After Transcatheter Aortic Valve Implantation

“…12,13) The aim of our study was to assess the incidence and predictors of VARC-2 bleeding complications in patients undergoing TAVI and to determine their impact on mid-term prognosis.…”

“…11) To address the issue of heterogeneous reporting of outcomes in patients undergoing TAVI, in 2011 the Valve Academic Research Consortium (VARC) developed a set of unified criteria for standardized definition of clinical endpoints, which were recently updated and published as VARC-2. 12,13) The aim of our study was to assess the incidence and predictors of VARC-2 bleeding complications in patients undergoing TAVI and to determine their impact on mid-term prognosis.…”