| Article Access Statistics|
| Viewed||2716 |
| Printed||25 |
| Emailed||0 |
| PDF Downloaded||33 |
| Comments ||[Add] |
Click on image for details.
|LETTERS TO EDITOR
|Year : 2018 | Volume
| Issue : 2 | Page : 526-528
Commentary: Theranostics for stroke: Precision medicine is about tailoring therapy to the mechanism of ischemia
David S Liebeskind
Neurovascular Imaging Research Core and UCLA Stroke Center, University of California, Los Angeles, CA, USA
|Date of Web Publication||15-Mar-2018|
Dr. David S Liebeskind
Neurovascular Imaging Research Core, 635 Charles E Young Drive South, Suite 225, Los Angeles, CA 90095-7334
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Liebeskind DS. Commentary: Theranostics for stroke: Precision medicine is about tailoring therapy to the mechanism of ischemia. Neurol India 2018;66:526-8
Theranostics is an intuitive, yet nascent concept of precision medicine that aims to provide the right therapy for the right patient at the right time. Malhotra et al., invoke this paradigm in their recent article on the therapeutic strategies for individuals with acute ischemic stroke on apixaban. They underscore the profound advances in stroke prevention for atrial fibrillation in the last decade, including the availability of numerous novel anticoagulants (NOACs) to safely and effectively reduce the devastating impact of cardioembolic stroke. Despite this recent transformation in the management of atrial fibrillation, there remain a wide array of questions that challenge clinicians in the optimal management of stroke when stroke occurs while the patients is on such an anticoagulation. Malhotra et al., provide important considerations and their own recommendations in this scenario, while they raise important questions germane to the emerging development of precision medicine for stroke.
The clinical dilemma posed by Malhotra et al., of an acute ischemic stroke developing while the patient is on apixaban, questions the role of this particular therapy in apparent failure of stroke prevention. The authors astutely suggest that compliance or drug interactions, the mechanism of ischemia and other factors should be considered. They wisely underscore the need to focus on patient-specific factors such as adherence to a proper medication schedule and proper determination of stroke etiology, leveraging a thorough diagnostic evaluation including the use of neuroimaging. Without such a comprehensive strategy, clinicians may simply diagnose “stroke” and have no logical rationale for subsequent stroke prevention approaches. The authors underscore the hemorrhagic risk, yet this concern regarding NOACs has likely been overblown with only marginal focus on the prevention of recurrent disabling events, known to be more devastating than strokes due to other causes. The cited need for reversal agents of such anti-thrombotics is also questionable, as reperfusion may be enhanced with such medications and the additional detrimental effect of NOACs in intracranial hemorrhage may be ill-defined. They outline the evidence for superiority of apixaban, as well as the impact of imaging on determination of stroke etiology and patient-specific factors such as compliance and metabolism that may frequently be overlooked. These considerations are important in the management of stroke, yet they represent only the most superficial aspects of precision medicine in stroke. The authors properly invoke the role of underlying pathophysiology when considering therapies for a given individual and they expand the often narrow concept of precision medicine to be focused around genetic predisposition such as pharmacogenomics while ignoring social or environmental factors such as compliance. The authors touch upon only succinct facts from the recent literature on NOACs and suggest future approaches to resolve current limitations in evidence, yet they also fall prey to the dangers of reductionism that threaten a more holistic perspective in precision medicine.
Theranostics is contingent on the availability of data that relate to the individual in question, and simultaneously, the broader population. Simplistic generalizations from large randomized, controlled trials (RCTs) may not properly address key details such as ischemic pathophysiology or concomitant factors that impact long-term brain health. Even the recent RCTs that catapulted NOACs into the clinic did not comprehensively address influential imaging characterization of stroke etiology, silent infarcts or longitudinal evaluation of brain resilience that may profoundly affect long-term neurological outcomes. The diagnosis of “stroke” may be overly reductionist, similar to the misconception that prescribing apixaban to a patient may not be affected by individual pharmacogenomics or compliance issues. Only 20 years ago, stroke prevention was primitively focused predominantly around anti-thrombotic medications whereas other risk factors such as dyslipidemia or diabetes were often neglected. Even our definitions of hypertension have lagged until recently. Clinicians would routinely advance stroke patients up the rungs on the anti-thrombotic ladder, iteratively switching therapies based on the determination of prior drug failure. In recent years, it has become apparent that medication adherence and pharmacogenomics may impact the effectiveness of antithrombotic agents in stroke prevention. Increasingly routine use of imaging to determine the mechanism of ischemia and concomitant pathology such as carotid stenosis may disclose other factors that are important in developing secondary stroke prevention measures for patients who have an acute ischemic stroke while on apixaban. Limited data or reductionism currently plagues our stroke management strategies when atrial fibrillation is identified. It has become apparent that detection of atrial fibrillation may be drastically improved with novel implantable devices and long-term surveillance techniques. The recent Food and Drug Administration (FDA) approval of mobile health technology for individuals to self-diagnose atrial fibrillation will radically expand the previously reductionist or limited approach to atrial fibrillation determined at the time of hospital admission for stroke. Reductionism is also erroneously enacted when a clinician identifies atrial fibrillation, yet it is not causative in stroke etiology. For example, apixaban is unlikely to address concomitant carotid stenosis as a cause of stroke, despite its role in preventing cardioembolic stroke. The authors should not focus exclusively on apixaban, as there is likely a class effect for an entire array of novel anticoagulants and the authors are thereby committing a reductionist error of identifying such a narrow perspective to anticoagulation. The apparent superiority of apixaban has also not been unequivocally proven by head-to-head trials of NOACs, yet such studies are unlikely to ever occur. Registries are the most likely sources of such important data in the future, where the vast divergence of numerous other important variables will be most fruitful.
The future of precision medicine in stroke and the realization of theranostics critically depends on data, about the individual stroke patient and the larger population. The dilemma posed by Malhotra et al., provides yet one example of the current false simplicity in the complex pathophysiology of ischemic stroke. Clinicians must consider mechanisms of ischemia, concomitant risk factors and the long-term impact of cerebrovascular disease on brain health. The episodic and limited focus on acute ischemic stroke must be considered in light of chronic cerebrovascular disease that imperils brain health on a global level. Our field must transition from the overwhelming reductionist focus on solitary therapies such as apixaban for atrial fibrillation and develop a more sophisticated approach to cerebrovascular disease centered on the foundation of large scale data.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Malhotra K, Ramanathan SR. Acute Ischemic Stroke on Apixaban: What Next? Neurol India 2018;66:525-6. [Full text]
Hinman JD, Rost NS, Leung TW, Montaner J, Muir KW, Brown S, et al
. Principles of precision medicine in stroke. J Neurol Neurosurg Psychiatry 2017;88:54-61.
Liebeskind DS, Feldmann E. Imaging of cerebrovascular disorders: Precision medicine and the collaterome. Ann N
Y Acad Sci 2016;1366:40-8.
Greene JA, Loscalzo J. Putting the patient back together-social medicine, network medicine, and the limits of reductionism. N
Engl J Med 2017;377:2493-2499.
Liebeskind DS. Mapping the collaterome for precision cerebrovascular health: Theranostics in the continuum of stroke and dementia. J Cereb Blood Flow Metab 2017:271678X17711625.