Cerebrovascular Disease, Vascular Dementia, Carotid Artery Disease, and CVA: Diagnosis, Prevention, and Treatment



Cerebrovascular Disease, Vascular Dementia, Carotid Artery Disease, and CVA: Diagnosis, Prevention, and Treatment


Alfred S. Callahan III, MD



Cerebrovascular disease or stroke can be separated into ischemic or hemorrhagic with ischemic events predominating often 3:1. Despite the importance of hemorrhagic stroke, this section is devoted to ischemic stroke.


Acute Ischemic Stroke


Rescue

The treatment era of acute ischemic stroke began in December 1995 with the proof of benefit when intravenous thrombolysis was administered within 3 hours of onset (NINDS) in selected subjects.1 Despite the scientific advance peripheral thrombolysis provided, translation of this benefit to stroke populations in the United States was slow. The next step in treatment was the demonstration of benefit in catheter-directed thrombolysis in the middle cerebral artery within 6 hours.2 However, intra-arterial thrombolysis required cath lab availability, which was limited in the late 1990s. Even extension of the peripheral thrombolysis benefit from 3 to 4.5 hours due to the results of ECASS3 did not increase the number of treated patients.3 The next step in treatment had to await the development of stent retrievers for clot extraction. In December 2014, mechanical thrombectomy was shown to provide benefit beyond peripheral thrombolysis (MR CLEAN). And, by February 2015 multiple trials showed benefit with mechanical thrombectomy in the anterior circulation compared with peripheral thrombolysis (REVASCAT, Swift Prime, Extend IA, Escape). With the advent of advanced imaging identification of reversibly ischemic brain, the time window for treatments was extended up to 24 hours in selected cases (Defuse 3, DAWN). At last the tissue clock eclipsed the time clock for identification of those who might benefit from rescue treatment.

With these advancements more emphasis has been placed on systems of care beginning with public recognition of transient ischemic attack (TIA)/stroke, prehospital packaging, and development of comprehensive stroke centers with endovascular treatment expertise. Now more than ever where you go for health care can make a certain difference given rescue’s proven scientific benefit.




Prevention (Primordial/Primary/Secondary)


Risk

With the publication of NASCET in 1991, it was clear that activated carotid plaque with at least 70% stenosis was best managed by surgical removal (carotid endarterectomy). Subjects with 50% to 69% stenosis were the subject of another publication by the NASCET group in 1998. This group with moderate to severe stenosis had subgroups who were benefited with surgical revascularization. But included in the publication was a figure of the original NASCET cohort since 1991.9 The group with severe stenosis had ipsilateral strokes for 3 years, and then for the next 5 years had a stroke rate equal to those who had their carotid plaques removed. Only 25% of the group randomized to medical care had a subsequent stroke, but 75% did not. This graph suggested that despite severe symptomatic stenosis in a large
capacitance precerebral artery active plaques might become stable over time. But, the article did not indicate why or how this might have occurred.

Another example of the change in risk over time can be shown with the placebo groups in peripheral thrombolysis studies of acute ischemic stroke. The initial NINDS publication in 1995 had a placebo death rate of >20%.10 By 2008 (13 years later) in the extended time window study,11 the placebo death rate was 8.2%. When death is less, the relative benefit from treatment is also less against the comparator. Trialists have experienced changing risk when vascular event rates were lower than predicted requiring expansion of their study population to retain statistical power.

The change (decrease) over time in levels of risk has been influenced by the advent of better antihypertensives, intensive lipid-lowering medications, and better access to cath labs for urgent reperfusion. And it may also be that the sickest have fallen first and earlier from the present (Darwinian selection). Historic risk may not be a guide to present or future risks as contemporary treatment(s) may have made a difference.


Stroke Type/Mechanism


Large Vessel Disease/Occlusion


LOW HANGING FRUIT-ATRIAL FIBRILLATION

Atrial fibrillation accounts for about 15% of all acute ischemic strokes and the majority of disabling strokes. As the most common adult arrhythmia ensuring a high prevalence and the left atrial appendage being able to produce large volume clots, it is not surprising that devastating strokes occur since the first two vessels off the aortic arch provide the anterior circulation of the brain.






Figure 30.2 Underuse of oral anticoagulation in atrial fibrillation patients. (Reproduced from Waldo AL, et al. Hospitalized patients with atrial fibrillation and a high risk of stroke are not being provided with adequate anticoagulation. J Am Coll Cardiol. 2005;46:1729-1736, with permission from Elsevier.)

Cardiocerebral embolism is more apt to produce death, hemorrhagic conversion, nursing home placement, dependency than other etiologies of ischemic stroke (Lisbon #24). And because the affected population is older, it is no surprise that women are the majority of patients.

Adjusted dose warfarin has been known since the 1960s to reduce the absolute ischemic stroke rate by 4% and provide for relative risk reduction of 75+%. Despite the known benefit of such treatment, a large untreated population exists worldwide (Figure 30.2). The difficulty of dosing with a narrow therapeutic index agent, interactions with diet requiring careful patient adherence to choice of foods, slow onset of effectiveness, frequent interaction with other medications, high protein binding, and the concern of causing brain hemorrhage have all limited the use of effective treatment with warfarin.

Effective alternatives to adjusted dose warfarin were introduced into clinical practice in 2008 with dabigatran an oral direct thrombin inhibitor. By 2011 the first of the anti-Xa agents was approved for the reduction of risk in atrial fibrillation (rivaroxaban) and by the end of 2012 a second (apixaban) was approved for the same indication. There are currently three anti-Xa agents available. These new classes of agents do not require dietary modification or routine monitoring. They are fully active within 3 hours and have short half-lives. Antidotes to oral direct thrombin inhibitors and anti-Xa agents are now available.

Algorithms to stratify risk in atrial fibrillation have been modified to provide an extra point for female gender and two additional points for age (>65 and >75 years). Using CHA2DS2-VASc helps identify more subjects at risk who would be benefited by oral anticoagulation.12,13

Bleeding algorithms are not as well prospectively validated but are available (Figure 30.3). Bleeding remains the largest safety issue with oral anticoagulation, especially
intracranial hemorrhage. Some of the newer agents have a safety profile improved over warfarin (Aristotle) and have rearranged the landscape or geography of complicating hemorrhage. GI hemorrhage remains the last frontier to be addressed and modified with the newer agents.

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Feb 27, 2020 | Posted by in CARDIOLOGY | Comments Off on Cerebrovascular Disease, Vascular Dementia, Carotid Artery Disease, and CVA: Diagnosis, Prevention, and Treatment
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