This article is more than 5 years old. Information may no longer be current.
Consensus statement proposes standardized neurologic endpoints for CV trials
Click Here to Manage Email Alerts
The Neurologic Academic Research Consortium, composed of researchers from the United States and Europe, recently published a consensus statement calling for standardization in the definition and assessment of neurologic endpoints in CV clinical trials to enhance the evaluation of neurologic and cognitive benefits and risks.
“The current stroke definitions used in [CV] trials focus on the most extreme, devastating strokes, which are only one component of a spectrum of brain injury that is relevant to patients with [CVD],” Alexandra Lansky, MD, a member of the Neurologic Academic Research Consortium (NeuroARC), told Cardiology Today’s Intervention.
She noted that while more nuanced measures of neurologic injury are standard in the setting of neurology trials of acute stroke, they have not been widely used in cardiovascular trials and were not designed for the particular challenges of CV therapy assessment. “Because trials that combine a neurologist evaluation and sensitive brain imaging have found higher stroke rates than previously reported, as well as frequent subtle neurologic injury and clinically silent cerebral infarction, it is clear that these outcomes require increased attention,” Lansky, professor of medicine in the section of cardiology at Yale School of Medicine, said. “We believe that the proposed endpoints and assessment framework will better characterize the true risks of CV procedures and the benefits of preventive therapies, ultimately leading to more informed clinical decision-making and improved patient outcomes.”
Important highlights
A major goal in drafting the recommendations in the consensus statement was development of new nomenclature to simplify classification into three main types of potential damage to the brain.
According to the new classification, Type 1 is defined as overt injury to the central nervous system (CNS), which is acutely symptomatic. Type 2 is defined as covert CNS injury, which is asymptomatic despite documented damage on brain imaging. Type 3 is defined as neurologic dysfunction without CNS injury, which is acutely symptomatic but without imaging evidence of injury.
“By reclassifying neurologic damage based on the presence or absence of acute symptoms and imaging evidence of injury, we are able to capture the totality of neurologic injury, while maintaining historical consistency with the distinction between symptom-based and tissue-based definitions,” Lansky said.
This approach achieves a major goal of the NeuroARC consensus, which was to integrate existing definitions of neurologic injury and stroke, in particular definitions established by the American Stroke Association and those of the Valve Academic Research Consortium (VARC). “We’re adopting a lot of the recommendations that the ASA put forward,” she said. “They emphasize the importance of tissue-based diagnosis of stroke, and many of our proposed definitions are driven by imaging, particularly when trying to assess neuroprotection devices.” VARC is in the process of drafting a third set of guidelines, according to Lansky, which will likely be more in line with the NeuroARC recommendations, rather than earlier versions which were limited mainly to the most devastating strokes.
Additionally, the consensus statement provides a framework for tailoring the assessments of neurologic injury based on the specific device or procedure being evaluated in the trial, according to Lansky.
To facilitate this process, the NeuroARC group developed three categories. Category 1 involves devices or procedures for which evaluation of neurologic injury is a safety outcome, such as trials involving TAVR or CABG. Category 2 involves evaluation of neurologic injury as an efficacy measure, as is the case with neuroprotection devices. Category 3 includes devices or procedures for which neurologic injury is a combination of safety and efficacy outcomes, such as with left atrial appendage closure devices where implantation of the device may be associated with risk for embolization, but the long-term intent of the device is stroke prevention.
“It’s not one-size-fits-all,” Lansky said. “We’re sensitive to the fact that the methods need to adapt to the benefits and risk of the specific therapy and the goals of each trial. Rather than mandating specific trial designs, we have tried to provide flexible guidance on how to incorporate standard definitions and appropriate assessments into trials while minimizing the burden on sponsors and study sites.”
Lansky said the new emphasis on neurocognitive assessments is an important contribution of the NeuroARC recommendations. “Historically these have not been commonly assessed in clinical trials, but we know that cognitive function is an important predictor of quality of life and functional dependence, and evaluation of these outcomes can complement more traditional clinical and imaging assessments in providing a more complete picture of how these procedures affect patients.”
Implications
Overall, these recommendations are designed to provide a framework to improve assessment and reporting of stroke and other neurologic injury in CV trials, the NeuroARC group concluded.
“The main goal behind NeuroARC is for us to be able to report the full spectrum of neurologic injury associated with cardiac procedures and its clinical implications. This information is vital for an informed benefit-risk analysis of any cardiac procedure and in discussions with our patients,” Lansky said. “Also, importantly, these recommendations will facilitate the evaluation of new approaches to treat or prevent brain injury and improve our understanding of the mechanisms and predictors of these events.”
The consensus statement was published simultaneously in the Journal of the American College of Cardiology and the European Heart Journal. – by Melissa Foster
For more information:
Alexandra Lansky, MD, can be reached at alexandra.lansky@yale.edu.
Disclosure: Lansky reports receiving research grant support from Boston Scientific, Keystone Heart and NeuroSave Inc., and receiving speaker/consultant fees from Keystone Heart. Please see the full statement for a list of the other researchers’ relevant financial disclosures.
Click Here to Manage Email Alerts