Stroke Prevention and Acute Treatment - Jeffrey Saver, MD | UCLAMDChat

Aug 26, 2023

Stroke Prevention and Acute Treatment - Jeffrey Saver, MD | UCLAMDChat

UCLA neurologist Jeffrey Saver, MD tackles stroke, the leading cause of death and disability in the US. Dr. Saver will discuss lifestyle, medication and procedure treatments to prevent stroke and to reverse stroke injury once it starts. Learn more about the warning signs of a possible stroke and newly approved treatments available to patients.

Content

7.44 -> Hello everyone!

11.24 -> And welcome to the webinar today on stroke prevention and acute stroke treatment. I'm Dr. Jeffrey Saver. I'm the Director of the

19.05 -> Comprehensive Stroke and Vascular Neurology Program at the Ronald Reagan UCLA Medical Center,

24.96 -> and it's my great pleasure to speak with you today about how to prevent and treat this all-too-common problem.

33.15 -> As I give the talk today, please know that you have the ability to submit questions on Twitter using

41.19 -> #UCLAMDChat or by

43.559 -> comment on Facebook, and we'll try to answer some of them at the end. In

48.449 -> the course of the talk today, I'll be

51.51 -> giving an overview of stroke, talking about how to prevent stroke, talking about currently available

58.14 -> treatments for acute stroke, and then also talking about a new study

63.409 -> we're doing in the Los Angeles area of a

67.14 -> potential agent to treat stroke, the fast TSE stroke trial.

72.72 -> I'm speaking on behalf of all of my colleagues here at the UCLA

78.659 -> Comprehensive Stroke Center, which is one of the leading places in the world for the care of patients with neurovascular disease.

88.2 -> So let's begin with an overview of stroke. What is a stroke? Now, first of all, how common is it? It is the

96.539 -> leading cause of serious

98.999 -> disability in adults in the United States, and it is the fifth leading cause of death in the United States.

105.42 -> Moreover, it's the second leading cause of death worldwide and the second leading cause of death here in the County of Los Angeles.

113.549 -> So, more than 140,000 Americans will die from stroke this year, and nearly

119.399 -> 800,000 Americans will have a stroke this year.

122.579 -> There are more than 5 million people alive in the US who have survived a stroke, and

128.19 -> one in six people will have a stroke in their lifetime, a very common condition, and it is characterized by

135.87 -> Injury to the brain from blockage or rupture of a blood vessel.

140.94 -> There are two broad types of stroke. The first is

145.01 -> blockage of a blood vessel. That accounts for 80% of strokes, 4 out of 5,

149.849 -> where an area of the brain does not, again, get nutrients and oxygen because of a blockage, and

157.439 -> there's hemorrhagic stroke, bleeding stroke, which accounts for 20%,

162.03 -> 1 out of 5 strokes, due to a rupture of a blood vessel,

166.379 -> letting blood go into or around the brain.

173.4 -> The brain depends on a continuous supply of blood delivering oxygen,

180.72 -> glucose, nutrients, and carrying away waste products away from the brain.

186.48 -> And if something goes wrong with this

189.93 -> circulation system to the brain, then the brain will be injured, and as mentioned,

194.879 -> the two main types are having a blockage in a blood vessel,

199.2 -> cutting off oxygen and nutrients to an area, leading the cells to be injured, or

205.2 -> having a rupture of a blood vessel, causing bleeding into the brain. Ischemic or hemorrhagic stroke.

213.9 -> What are the signs that a stroke might be occurring and that you need to call the 9-1-1

220.44 -> system right away to be treated?

224.069 -> Stroke can cause many different symptoms because whatever the brain does can go wrong in a stroke.

229.139 -> But there are three common symptoms that we educate the public to be aware of, and they're captured in this mnemonic,

237.629 -> FAST. Face, Arm, Speech, Time.

242.519 -> FAST. F stands for drooping of the face on one side. A

250.079 -> stands for arm weakness on one side.

253.889 -> Speech difficulty is trouble speaking, slurred speech, or

258.599 -> incorrect speech, and if you have any of those symptoms, then it's T, time

264.389 -> to call 9-1-1 because it might represent a stroke taking place.

270.96 -> What is the outcome of stroke besides its sometimes leading to

276.06 -> fatal outcomes? It can cause

278.6 -> major permanent deficits and disabilities for patients. Two weeks after a stroke, nearly

285.6 -> 4 out of 5 people will have weakness on one side of the body. 3 out of 4 will have trouble walking.

291.75 -> 1 in 3 will have trouble speaking. 1 in 5, trouble with their vision.

297.349 -> Nearly half of patients will have depression, and

300.72 -> over half of patients will need help in everyday living.

306.419 -> Long term--six months after stroke,

309.9 -> nearly a third of patients will have passed away, and among the survivors nearly a third will require daily assistance,

317.34 -> including help with walking. 1 out of 6 people will be permanently in a skilled nursing facility, and

324.78 -> 3/4 of people who had a stroke would not be able to return to work or full

329.729 -> daily activities. So, this is a condition we all want to avoid.

336.18 -> Now, who is at increased risk for stroke?

340.77 -> Communities at and people at increased risk include older individuals.

345.69 -> 2/3 of all strokes occur in people over the age of 65. Stroke can also occur in childhood and

354.03 -> adolescence, in midlife, it's very common there, but it's especially common in older individuals.

360.419 -> African Americans have higher rates of stroke and more severe strokes than other ethnic groups, and

366.81 -> Hispanics have higher rates of stroke than non-Hispanics.

371.219 -> Individuals who had a prior stroke have a very increased risk--tenfold increased risk, and here in Los Angeles in

378.479 -> general, there's a geographic increased risk with higher rates than in surrounding counties.

385.77 -> Well, what can you do to reduce this risk and to prevent stroke? And here are some of the

393.3 -> modifiable and non-modifiable risk factors.

396.9 -> Non-modifiable risk factors, we've already mentioned age--can't do very much about that.

402.449 -> Gender--there are more strokes at any particular age in men, but more women overall have strokes because they live longer.

409.74 -> The race, ethnic groups we've talked about, and heredity--if you've had a

415.47 -> parent who had a stroke, your risk of stroke is about 1 1/2-fold increase, but the good news is there are many

421.83 -> modifiable risk factors for stroke. These include medical conditions that can be treated if they've been diagnosed--high blood pressure,

429.54 -> having the abnormal heart rhythm of atrial fibrillation,

432.96 -> having diabetes mellitus,

435.57 -> having a blockage in the carotid artery or carotid stenosis,

438.93 -> all of those are highly treatable risk factors for stroke that, if well controlled, can

444.93 -> prevent stroke, and then there are behaviors that are vessel healthy.

452.46 -> Cigarette smoking, heavy alcohol use, physical inactivity--

457.32 -> damages blood vessels, causes heart attacks and strokes, and by avoiding those behaviors,

462.26 -> you can reduce your risk, and the good news is that overall,

467.22 -> stroke is highly preventable.

469.62 -> 90% of all strokes can be prevented just by

474.45 -> taking care of these simple health promoting activities--

478.68 -> having regular physical activity,

480.96 -> having a diet that is not high in salt or fats, not smoking, not having too much alcohol,

489.3 -> controlling cholesterol levels and blood pressure,

493.47 -> avoiding being overweight, and

496.71 -> with these simple measures, you can reduce your risk of stroke

502.68 -> dramatically by 90%.

505.23 -> Now, in addition to general risk factor management,

508.37 -> there are a few specific treatments helpful for people who have particular

512.16 -> conditions. If you have a cholesterol plaque buildup, atherosclerosis,

517.32 -> cholesterol plaque buildup in an artery going to the brain, either in the neck or in the

524.07 -> intracranial head arteries, then

526.74 -> cholesterol-lowering medicines can be helpful, and

529.83 -> aspirin and other antiplatelet medicines to keep clots from forming on the

534.72 -> abnormal plaque surface can be helpful.

537.03 -> If you have a narrowing from a plaque in the carotid artery in the neck, then procedures can be done

544.88 -> to reopen that artery and remove or reduce the narrowing, either by doing a surgery--carotid endarterectomy,

553.29 -> to open the artery and take the plaque out, or a procedure--carotid angioplasty and stenosis, where the

562.17 -> interventionist put a wire in an artery in the leg and advance it to the neck, and from the inside,

567.42 -> expand a balloon and put in a stent to hold the artery open, and those can reduce stroke risk.

572.36 -> And then if you have the abnormal heart rhythm of atrial fibrillation, a

577.65 -> different class of anticlotting medicines--the

580.71 -> anticoagulant medicines are very good at keeping clots from forming

584.34 -> in the heart in patients who have atrial fibrillation and breaking off and travelling to the brain.

591.3 -> So, in summary,

593.01 -> here are key take-home messages for you to prevent stroke.

597.3 -> Do aerobic activity 20-60 minutes every day,

600.74 -> even if it's just simple walking. Eat a diet low in saturated fats, rich in vegetables. Don't smoke, don't drink alcohol to excess,

609.33 -> control blood pressure, cholesterol, and diabetes, and take anticlotting medicines if you have atrial fibrillation.

617.31 -> Now, let's turn to how we treat an acute stroke. If

621.57 -> prevention hasn't worked and a stroke is happening,

624.6 -> and I'm going to focus on the most common type of stroke, the ischemic

628.68 -> blockage stroke, which accounts for more than 4 out of 5 strokes--and

633.66 -> when blood flow is cut off to a region of the brain,

638.25 -> unfortunately, injury starts happening very quickly. Every minute that goes by

643.41 -> before we're able to restore blood flow, two million more nerve cells are lost.

648.87 -> So, time lost is brain lost in acute stroke.

652.92 -> We have some standard supportive treatments we do for all stroke patients.

658.89 -> Avoiding having the body temperature get too high, giving oxygen if the oxygen is too low, and

667.05 -> giving fluids to maintain the patient's

671.52 -> usual blood pressure and hydration status. That helps a little bit.

676.41 -> But the most important and effective treatments are to reopen the blocked artery and

682.18 -> restore blood flow to the threatened brain before the injury has fully injured that part of the brain, and we have a few

689.53 -> minutes to hours in which to do that. There are two main

694.33 -> treatments to reopen blocked arteries. One is to give a drug, Tissue Plasminogen

699.91 -> Activator, TPA, that dissolves the blockage. It's kind of like a Drano for

706 -> blockages in the arteries, and the other is to put up a device

711.19 -> with a wire, again, through an artery in the leg and advance it into the head and grab the clot and

717.79 -> pull it out, fish it out with a

720.64 -> state retriever device or a suction device. So that's kind of Roto-Rooter, to open the blocked artery, and

729.61 -> these treatments are very time important.

733.51 -> Every 8 minutes that goes by, one less patient benefits from the clot dissolving

739.3 -> medicine. Every 4 minutes that goes by, one less patient

743.59 -> benefits from the artery

746.86 -> reopening retriever device, so we tell patients you have to get to the hospital as soon as possible.

753.01 -> These treatments are best and most effective when used in the first 1-3 hours after onset.

759.28 -> They can help some patients as late as 24 hours after onset,

764.2 -> if the patient happens to have a slowly evolving stroke, but not all patients do, so

769.56 -> it is important to get to the hospital as quickly as possible if you're having any of the stroke symptoms.

776.5 -> However, these current treatments we're only able to use in about 1 in 10 patients,

782.98 -> for a variety of reasons. Patients have contraindications to the drug, arrived too late, have too mild strokes, or other reasons.

790.44 -> So our current treatments are only available for 1 in 10, and 9 in 10 patients have no specific therapies,

797.26 -> which is why we need to develop additional treatments, and

802.54 -> that is the reason that we've undertaken this PHAST-TSC trial.

809.98 -> The purpose this trial is to find out if a

814.23 -> agent called trans sodium crocentinate, TFC,

819.12 -> injected into the vein by paramedics in the ambulance in acute stroke patients in the first two hours will improve the outcome of

827.19 -> acute stroke patients. Now, in general, drugs for stroke are

832.98 -> two types that are being developed. One has already worked. That's the clot dissolving

838.92 -> class of drugs like TPA, which reopens the blocked artery.

844.38 -> But to give that drug,

846.54 -> we can't give that in the ambulance because that drug is only for the blockage stroke. It makes those patients better,

852.829 -> but it hurts the bleeding stroke. It makes those patients worse.

855.86 -> So, we can't give TPA until after we've done a CAT scan or MRI scan in the hospital.

862.199 -> The other class of drugs that are being developed are neuroprotective drugs. They

867.66 -> allow nerve cells to tolerate low blood flow longer. They block the molecular

873.69 -> paths of injury when cells are not getting enough oxygen.

877.769 -> Those agents can be given in the standard ambulance because

882.959 -> they should be safe and possibly helpful for both the blockage and bleeding type of stroke.

891.6 -> Trans sodium crocentinate, TSC, is one of those types of agents. It's a molecule in the carotenoid family, which is the

900.029 -> type of molecules that make carrots orange, and it is an oxygen diffusion enhancer.

906.47 -> it increases the passage of oxygen into the

910.35 -> cells of the body, and that's been shown to help reduce stroke size in

916.62 -> animal and preclinical models of stroke. And this agent has also been found safe in

922.949 -> early studies in humans for other non-stroke conditions.

928.41 -> Therefore, we're testing it now in this PHAST-TSC study,

931.92 -> which is a study of 160 patients traveling in ambulances

937.259 -> to hospitals. Like all studies, the only way we can tell if the drug works is to compare it with

944.01 -> an inactive substance in a blinded way, so half the patients will be getting active TSC, and half will be getting placebo

951.6 -> saltwater. We're doing this here in Los Angeles and in central Virginia at

957.97 -> 23 hospitals, 20 here in Los Angeles. It's funded by Diffusion Pharmaceuticals, a

964.72 -> company in Virginia. Here in Los Angeles,

967.68 -> we're training 1,000 paramedics in the study who will be enrolling in 15 EMS provider agencies and 80

975.85 -> ambulances bringing patients to this consortium of 20 stroke centers in the County of Los Angeles that have come together to do this study.

986.05 -> Who qualifies for enrollment in the study? Patients who have weakness on one side of the body, are between age 40 and 95,

994.21 -> whose symptoms started within the last two hours

997.57 -> but beyond 15 minutes ago.

1000.42 -> What will happen if you qualify and are put in the study?

1003.84 -> You'll receive all standard treatments for stroke, and you'll be randomly assigned to also receive the TSC

1011.73 -> agent or placebo in a one-time injection in the ambulance.

1016.2 -> Then you will undergo brief 5-minute exams during--

1021.84 -> on arrival and at 24 hours, 2 days, and 4 days in the hospital, and then brief follow-up, phone and in-person

1029.76 -> visits 1 month and 3 months after the stroke to see the final evolution of the stroke after this treatment.

1039.3 -> What are the potential risks of this agent?

1041.51 -> Well, the agent's been developed with FDA oversight and tested in a variety of medical conditions, and at the dose employed in this study,

1049.32 -> no serious side effects have been detected.

1052.98 -> At the dose in this study, there are

1056.1 -> non-serious, uncommon side effects reported. Less than 3% of patients have had some skin or vein

1063.06 -> irritation at the site of injection, and even fewer have reported a

1067.23 -> transient warm feeling in the legs. And at much higher doses than we're doing in this study,

1072.18 -> some patients have reported some transient yellow color to the vision.

1077.22 -> What are the potential benefits of being in this study? Well, based on the experience with this drug in animals and patients with similar disorders,

1085.26 -> researchers believe that this agent may be helpful to subjects in

1090.42 -> improving their outcome from stroke with reduced brain injury and better

1095.04 -> ability to care for themselves. Of course, if patients receive the inactive placebo, they would not receive direct benefit from being in the study.

1103.29 -> How will patients be enrolled in this study? Well, if a

1108.48 -> patient's having a stroke, if you're having a stroke and you're still able to think for yourself,

1112.44 -> then we'll ask you if you would like to be in the study,

1115.89 -> and if there's a doctor able to speak with you directly in the ambulance by

1125.34 -> telemedicine, the doctor will speak with you and go through a full informed consent.

1132.51 -> If you're not able to think for yourself because the stroke has altered your language or ability to think for yourself,

1140.43 -> then the doctor will try to speak with a legally authorized

1145.14 -> representative, a family member or other person who's empowered to make decisions for you, and

1152.43 -> if that type of person is not with you but there's someone else with you who knows you well,

1157.32 -> then we'll speak with that person, and

1161.58 -> also, if we can't speak to you by video, the doctor can't directly interact with you,

1166.94 -> then the paramedics will briefly tell you or the decision-maker

1171.51 -> about the study, and

1173.64 -> a brief affirmative response from you will let us get the study started.

1181.41 -> Now, if you're not able to make decisions

1184.41 -> for yourself, and there's no one with you

1186.98 -> who knows you well, we don't know enough about your history to safely put you in the study,

1192.51 -> so you won't be put in the study.

1195.54 -> You'll get standard treatment for your stroke.

1199.23 -> Now, if you know ahead of time, you don't want to participate in the study, that's fine.

1205.26 -> Let us know, and we provide an armband that--a

1208.92 -> wristband that people can wear to know that if they have a stroke, they don't want to be in the study.

1215.55 -> To do this type of study, where we enroll patients in the ambulance including after only

1221.4 -> brief discussion about the study, because of the emergency setting, the FDA has us go through a process of community

1229.5 -> consultation and public disclosure, and

1232.26 -> we get input from community leaders about the study, and we also have press releases and flyers and public meetings

1240.27 -> to let everyone know the study is being undertaken.

1244.83 -> This stroke clearly qualifies as an emergency condition for this type of enrollment

1253.23 -> process, under the exception from fully informed consent process

1257.28 -> because it is a severe, fatal, and often disabling condition.

1261.86 -> It needs to be treated very quickly, and prior treatments have not worked because they were started too late.

1267.86 -> And so the FDA has authorized this type of enrollment process for this PHAST-TSC trial.

1274.73 -> So we're very hopeful that with this study, we may be able to add to the ways to treat patients with stroke.

1282.09 -> But let me come back here at the end by reminding everyone

1286.02 -> the best way to treat a stroke is to keep it from happening in the first place, and as we discussed at the beginning,

1292.44 -> 90% of all strokes can be prevented by

1295.8 -> good control of risk factors and a healthy lifestyle. And we do have treatments for the more severe strokes

1301.86 -> if you get to the hospital early, so if you have any of the warning signs of a stroke, the Face, Arm, Speech signs

1309.15 -> taught, it's T, time to call 911 and get to the hospital quickly, so we can treat you. And

1316.53 -> we've had some questions come in over Twitter and Facebook,

1320.06 -> and so let me take a look at at those and talk about

1327 -> them, answer a couple of them.

1330.72 -> One question is

1332.55 -> "What drugs do we use for

1335.13 -> thrombolytic and blood thinners?" So, thrombolytic drugs are the clot dissolving drugs, and right now the only

1341.82 -> approved thrombolytic drug for stroke is Tissue Plasminogen

1346.059 -> Activator. There's another drug called Tenecteplase, which is a little easier to give, and there are some early studies

1354.34 -> suggesting it may be as good as Tissue Plasminogen

1358.45 -> Activator, and we and others are doing further studies to see if that

1363.13 -> could be a more effective way to treat patients. But right now, the standard is Tissue Plasminogen

1369.49 -> Activator. For the blood thinners, so the

1372.16 -> anticoagulant medicines, those are more in the prevention, not the acute side, and there's this new classes of drugs,

1378.87 -> the NOACs, the novel oral anticoagulant drugs

1384.82 -> like apixaban and dabigatran, that have

1388.84 -> now emerged, that have advantages over the old warfarin type of drug,

1394.54 -> which had a lot of food interactions and required a lot of blood tests to monitor. And so, we are

1401.29 -> preferentially, for most patients with atrial fibrillation,

1403.96 -> to prevent stroke, using these new NOAC medications.

1408.49 -> "How can people help the patient while waiting for paramedics to arrive with an acute stroke?" And

1415.179 -> first let me say, you know, it's important to call 9-1-1 when you're having stroke symptoms. Don't try to reach your doctor or

1422.89 -> neurologist. That wastes time trying to make a connection. Call 9-1-1, and we've trained all the paramedics in Los Angeles

1429.04 -> to recognize stroke in patients, and when they recognize stroke, they bring the patients to the nearest certified stroke center.

1436.29 -> So you can be sure, if you call 9-1-1, that you're going to be brought to a hospital

1440.53 -> that is an appropriate place to treat the acute stroke.

1444.88 -> People ask whether they should give a patient aspirin while they're waiting

1448.69 -> if they're having a stroke, and the answer to that is no because

1452.5 -> the aspirin might help the most common type of stroke, the blockage ischemic stroke,

1457.98 -> it could make the less common type of stroke, the bleeding stroke, worse, and without a CAT scan,

1463.38 -> we don't know which type of stroke is taking place. So,

1466.929 -> best not to give that,

1469.12 -> just to have the patient

1472.21 -> lie down and stay with them until help comes, and

1477.38 -> "Can high cholesterol cause a stroke?"

1480.65 -> And the answer is yes, high cholesterol is a risk factor for atherosclerotic plaque,

1487.7 -> cholesterol plaques, to build up in the arteries, and

1494.75 -> 1 out of 2 strokes, 50% of ischemic strokes, are due to plaque buildup in large or small arteries.

1502.37 -> So, eating a healthy diet that keeps cholesterol down and taking cholesterol-lowering medicines if

1508.31 -> necessary can help to prevent stroke.

1511.55 -> So with that, I will thank you all for joining us today,

1517.06 -> and I hope you found this information on on stroke prevention, acute treatment, and this new PHAST-TSC

1524.63 -> study illuminating and helpful, and thanks very much for being part of the webinar.

Source: https://www.youtube.com/watch?v=pDfB0s2oyIw