Name:
A 68-Year-Old Man with Weakness
Description:
A 68-Year-Old Man with Weakness
Thumbnail URL:
https://cadmoremediastorage.blob.core.windows.net/82c154b2-9ba0-4092-89b0-1660e8ee243c/thumbnails/82c154b2-9ba0-4092-89b0-1660e8ee243c.jpg?sv=2019-02-02&sr=c&sig=jYmyuyvxV4hrvfomIpG%2BIcuLz%2FCoEehlBAPLJ3P2i4Q%3D&st=2024-05-04T00%3A19%3A52Z&se=2024-05-04T04%3A24%3A52Z&sp=r
Duration:
T00H11M37S
Embed URL:
https://stream.cadmore.media/player/82c154b2-9ba0-4092-89b0-1660e8ee243c
Content URL:
https://cadmoreoriginalmedia.blob.core.windows.net/82c154b2-9ba0-4092-89b0-1660e8ee243c/18892538.mp3?sv=2019-02-02&sr=c&sig=n%2FpAMSI%2FJ%2F8HGCjSOq67Sct2O4eQcX5oH8Selapr2sc%3D&st=2024-05-04T00%3A19%3A53Z&se=2024-05-04T02%3A24%3A53Z&sp=r
Upload Date:
2022-02-28T00:00:00.0000000
Transcript:
Language: EN.
Segment:0 .
[upbeat intro music]
DR. HANDY: Hi, welcome to Harrison's Podclass where we discuss important concepts in internal medicine. I'm Cathy Handy.
DR. WIENER: And I'm Charlie Wiener, and we're coming to you from the Johns Hopkins School of Medicine. Welcome to episode 65, a 68-year-old man with weakness. Here's the case, Cathy. A 68-year-old man presents to the emergency room with right-sided face, arm and leg weakness that began abruptly about one hour prior to arrival. The patient was brought in by his wife who can give a good history. The patient is awake and alert, he clearly understands questions but has trouble answering because he can't find the right words and has dysarthria.
DR. WIENER: His physical examination confirms a dense hemiparesis of the right face, the right arm and the right leg with decreased sensation in all. His reflexes on the right are diminished, but on the left are normal. In addition, there is a gaze preference to the left.
DR. HANDY: Based on this alone, this patient should be immediately evaluated for ischemic stroke. The pneumonic to remember for warning signs of stroke is FAST or F for face drooping, A for arm weakness, S for speech difficulty and T time to call 911. And this patient has those.
DR. WIENER: How would you characterize his aphasia?
DR. HANDY: It sounds like a classic Broca's aphasia which is a fluent aphasia with difficulty finding words but intact comprehension. This can be very frustrating to patients who experience it.
DR. WIENER: Okay. Let's get back to your initial thought because our clinicians were thinking the same. An emergent non-contrast head CT showed no evidence of intracranial hemorrhage or edema but there was only mild loss of gray-white matter differentiation diffusely. So the team is thinking of administering intravenous recombinant tissue plasminogen activator or tPA for this patient.
DR. HANDY: Yeah, I would agree with that assessment. The National Institute of Neurological Disorders and Stroke or NINDS had a study, the rtPA stroke study that showed a clear benefit for IV tPA in selected patients with acute stroke. This study used IV tPA versus placebo in ischemic stroke within 3 hours of onset of symptoms. One half of the patients were treated within 90 minutes and symptomatic intracranial hemorrhage occurred in 6.4% of patients on the tPA arm and 0.6% on placebo.
DR. HANDY: In the tPA group, there was a significant 12% absolute increase in the number of patients who only had minimal disability.
DR. WIENER: Okay. That's pretty impressive. But what about mortality and morbidity? You mentioned a much higher risk of intracranial hemorrhage.
DR. HANDY: In that study, there was a non-significant 4% reduction in mortality in the tPA group. So despite an increased incidence of symptomatic intracranial hemorrhage, treatment with IV tPA within 3 hours of the onset of ischemic stroke, overall improves clinical outcomes.
DR. WIENER: Okay. But is that the final answer? What about things like age and timing?
DR. HANDY: Yes, so it does get a bit more complicated. So three subsequent trials of IV tPA did not confirm the benefits of that initial study, perhaps because of the dose of tPA used or the timing of its delivery and then variations in the sample size. When data from all randomized IV tPA trials were combined however, efficacy was confirmed in the less than 3 hour time window and the efficacy likely extended to 4.5 and possibly even 6 hours.
DR. HANDY: Based on these combined results, the ECASS III study explored the safety and efficacy of tPA in the 3 to 4.5 hour time window.
DR. WIENER: And what did that study show?
DR. HANDY: Unlike the original NINDS study that I mentioned, patients who were over the age of 80 and diabetic patients with a previous stroke were excluded. In this 821 patient randomized study, efficacy was again confirmed, although the treatment effect was less robust beyond 3 hours than in the 0 to 3 hour time window. In the tPA group, 52% of patients achieved a good outcome at 90 days, and that's in comparison to 45% of patients in the placebo group.
DR. HANDY: The symptomatic intracranial hemorrhage rate was 2.4% in the tPA group and 0.2% in the placebo group. So based on these data, tPA is approved in the 3 to 4.5 hour time window in Europe and Canada but it's still only approved for 0 to 3 hours in the United States.
DR. WIENER: Wow. That's pretty complicated. But at the end of the day, would you give tPA to this patient?
DR. HANDY: I first need to make sure he doesn't have any contraindications to using the drug. So can you tell me more about that?
DR. WIENER: Yeah, so the patient's initial blood pressure on presentation in the emergency room is 220/140 and despite treatment with IV antihypertensive remains at 195/120. On further review of the patient's medical history, he has had a prior embolic stroke affecting the posterior circulation 12 months ago. He also has a history of colon cancer that was diagnosed three months ago when he presented with a lower GI bleed that required a transfusion.
DR. WIENER: He successfully underwent a left hemicolectomy of a stage 1 adenocarcinoma approximately three months ago.
DR. HANDY: Okay. So there's a lot of information here and this isn't going to be a simple decision.
DR. WIENER: Okay. Let's get onto the question because I think it's going to delve into some of these matters. The question asks, which of the following factors is a contraindication to the use of IV tPA in this patient? And the options are A. age greater than 65; B. blood pressure greater than 185/110; C. gastrointestinal bleed within the past three months; D. major surgery within the past three months; E. a prior embolic stroke; or F. none of these is a contraindication.
DR. HANDY: Well, let me go over the contraindications for tPA administration. So they are a sustained blood pressure over 185/110 despite treatment, a bleeding diathesis, a recent head injury or intracerebral hemorrhage, major surgery in the preceding 14 days, gastrointestinal bleeding in the preceding 21 days, or a recent myocardial infarction. So for this patient, he does have sustained hypertension despite treatment, so that would be the contraindication to administering tPA, and that would make the answer B.
DR. WIENER: And for the rest of the options?
DR. HANDY: Well, the other major thing that came up in his past history is his GI bleed in the setting of a colon cancer three months ago, but that's outside of the time period that would be considered a contraindication for tPA and he's had successful surgery. The prior embolic CVA that he's had is not a contraindication.
DR. WIENER: And I'm assuming that the persistent hypertension, the contraindication there is because it increases your risk of intracerebral hemorrhage?
DR. HANDY: Yes, that's right.
DR. WIENER: Okay. Well while we're talking about ischemic stroke, let's continue to discuss treatment. This is a two-part question. This patient did not get tPA because of his hypertension, as you articulated. The next question asks, which of the following antiplatelet agents has been proven effective in the acute treatment of ischemic stroke? And the options are A. aspirin; B. clopidogrel; C. dipyridamole; D. prasugrel; or E. ticagrelor.
DR. HANDY: So aspirin is the only antiplatelet agent that has been proven effective for the treatment of acute ischemic stroke. Two large trials, the IST and the CAST trial found that the use of aspirin within 48 hours of stroke onset reduced both stroke recurrence risk and mortality minimally. So in the first study, the IST trial, there were 19,435 patients. Those allocated to aspirin 300 mg per day had slightly fewer deaths within 14 days, significantly fewer recurrent ischemic strokes, no excess risk of hemorrhagic strokes, and a trend towards a reduction in death or dependence at six months.
DR. HANDY: In the CAST trial, 21,106 patients with ischemic stroke received 160 mg per day of aspirin or a placebo for up to four weeks. There were very small reductions in the aspirin group in early mortality, recurrent ischemic strokes and dependency at discharge or death. These trials demonstrate that the use of aspirin in the treatment of acute ischemic stroke is safe and produces a small net benefit.
DR. HANDY: For every 1,000 acute strokes treated with aspirin, about nine deaths or non-fatal stroke recurrences will be prevented in the first few weeks, and about 13 fewer patients will be dead or dependent at six months.
DR. WIENER: So it's important to distinguish that these trials were really only in acute strokes. This has nothing to do with secondary prevention of stroke.
DR. HANDY: That's exactly right.
DR. WIENER: And the effects of the aspirin were not nearly the size of effects you're talking about in the tPA. Are there any other agents that are used at all for patients who've had strokes?
DR. HANDY: The short term combination of clopidogrel with aspirin may be effective in preventing second stroke, but a number of trials did not show a benefit of clopidogrel in combination with aspirin for the treatment of acute stroke. A trial of over 5,000 Chinese patients enrolled within 24 hours of TIA or minor ischemic stroke found that the clopidogrel-aspirin regimen was superior to aspirin alone with the 90 day stroke risk decreased from 11 to 8% and no increase in major hemorrhage.
DR. HANDY: This benefit was limited to those not carrying the CYP2C19 polymorphism associated with clopidogrel hypometabolism. A similar trial of short term use of the combination of ticagrelor and aspirin in patients with mild non-cardioembolic stroke or TIA showed the risk of recurrent stroke or death within 30 days was significantly lower than with aspirin alone, making this combination an option for those patients who do not tolerate or are resistant to the effects of clopidogrel.
DR. WIENER: And what about dipyridamole?
DR. HANDY: So that's erratically absorbed depending on stomach pH but a newer formulation combines timed release dipyridamole with aspirin and has better oral bioavailability. The ESPS-2 study showed efficacy of both drugs in preventing stroke and a significantly better risk reduction when the two agents were combined. The open-label ESPRIT trial confirmed the ESPS-2 results. After three and a half years of follow-up, 13% of patients on aspirin and dipyridamole and 16% of patients on aspirin alone met the primary outcome of death from all vascular causes.
DR. HANDY: So the combination is approved for the prevention of stroke.
DR. WIENER: And why don't you use prasugrel?
DR. HANDY: There's a black box warning on prasugrel to not use it in patients with a history of TIA or stroke. So that would not be indicated here. That comes from a post hoc analysis of the TRITON-TIMI 38 data, where there was not a benefit, and even a harm to giving prasugrel in patients with a history of stroke or TIA. So it's not used in that scenario.
DR. WIENER: Okay. So the teaching points here are that in a patient with an acute ischemic stroke generally less than 4.5 hours an intravenous infusion of tPA is beneficial in terms of morbidity and recovered function. In patients with a contraindication to tPA, aspirin, possibly combined with another antiplatelet medication may also improve outcomes, although the magnitude of the improvement is not nearly that to the degree of tPA.
DR. HANDY: And if you want to learn more about this, you can check out the Harrison's chapter on ischemic stroke. [outro music] [Mr. Shanahan] This is Jim Shanahan, publisher at McGraw Hill. Harrison's Podclass is brought to you by McGraw Hill's Access Medicine, the online medical resource that delivers the latest trusted content from the best minds in medicine. Go to accessmedicine.com to learn more.