{"version":"1.0.0","segments":[{"startTime":0.471,"endTime":3.2,"body":"[upbeat intro music]"},{"startTime":3.2,"endTime":5.57,"body":"[Dr. Handy] Hi, welcome"},{"startTime":3.2,"endTime":5.57,"body":"to Harrison's Podclass"},{"startTime":5.57,"endTime":8.72,"body":"where we discuss important"},{"startTime":5.57,"endTime":8.72,"body":"concepts in internal medicine."},{"startTime":8.72,"endTime":9.85,"body":"I'm Cathy Handy."},{"startTime":9.85,"endTime":11.641,"body":"[Dr. Wiener] And I'm Charlie"},{"startTime":9.85,"endTime":11.641,"body":"Wiener, and we're coming to you"},{"startTime":11.641,"endTime":15.783,"body":"from the Johns Hopkins School of Medicine."},{"startTime":15.783,"endTime":20.42,"body":"Welcome to episode 65, a"},{"startTime":15.783,"endTime":20.42,"body":"68-year-old man with weakness."},{"startTime":20.42,"endTime":22.0,"body":"Here's the case, Cathy."},{"startTime":22.0,"endTime":24.38,"body":"A 68-year-old man presents"},{"startTime":22.0,"endTime":24.38,"body":"to the emergency room"},{"startTime":24.38,"endTime":27.54,"body":"with right-sided face,"},{"startTime":24.38,"endTime":27.54,"body":"arm and leg weakness"},{"startTime":27.54,"endTime":31.046,"body":"that began abruptly about"},{"startTime":27.54,"endTime":31.046,"body":"one hour prior to arrival."},{"startTime":31.046,"endTime":32.72,"body":"The patient was brought in by his wife"},{"startTime":32.72,"endTime":34.59,"body":"who can give a good history."},{"startTime":34.59,"endTime":36.17,"body":"The patient is awake and alert,"},{"startTime":36.17,"endTime":38.85,"body":"he clearly understands questions"},{"startTime":36.17,"endTime":38.85,"body":"but has trouble answering"},{"startTime":38.85,"endTime":42.34,"body":"because he can't find the"},{"startTime":38.85,"endTime":42.34,"body":"right words and has dysarthria."},{"startTime":42.34,"endTime":46.019,"body":"His physical examination"},{"startTime":42.34,"endTime":46.019,"body":"confirms a dense hemiparesis"},{"startTime":46.019,"endTime":49.83,"body":"of the right face, the"},{"startTime":46.019,"endTime":49.83,"body":"right arm and the right leg"},{"startTime":49.83,"endTime":52.27,"body":"with decreased sensation in all."},{"startTime":52.27,"endTime":54.64,"body":"His reflexes on the right are diminished,"},{"startTime":54.64,"endTime":56.36,"body":"but on the left are normal."},{"startTime":56.36,"endTime":59.3,"body":"In addition, there is a"},{"startTime":56.36,"endTime":59.3,"body":"gaze preference to the left."},{"startTime":59.3,"endTime":60.36,"body":"[Dr. Handy] Based on this alone,"},{"startTime":60.36,"endTime":62.71,"body":"this patient should be"},{"startTime":60.36,"endTime":62.71,"body":"immediately evaluated"},{"startTime":62.71,"endTime":64.27,"body":"for ischemic stroke."},{"startTime":64.27,"endTime":66.96,"body":"The pneumonic to remember"},{"startTime":64.27,"endTime":66.96,"body":"for warning signs of stroke"},{"startTime":66.96,"endTime":70.23,"body":"is FAST or F for face drooping,"},{"startTime":70.23,"endTime":71.95,"body":"A for arm weakness,"},{"startTime":71.95,"endTime":73.97,"body":"S for speech difficulty"},{"startTime":73.97,"endTime":76.58,"body":"and T time to call 911."},{"startTime":76.58,"endTime":78.23,"body":"And this patient has those."},{"startTime":78.23,"endTime":80.52,"body":"[Dr. Wiener] How would you"},{"startTime":78.23,"endTime":80.52,"body":"characterize his aphasia?"},{"startTime":80.52,"endTime":82.82,"body":"[Dr. Handy] It sounds like"},{"startTime":80.52,"endTime":82.82,"body":"a classic Broca's aphasia"},{"startTime":82.82,"endTime":85.84,"body":"which is a fluent aphasia"},{"startTime":82.82,"endTime":85.84,"body":"with difficulty finding words"},{"startTime":85.84,"endTime":87.8,"body":"but intact comprehension."},{"startTime":87.8,"endTime":91.47,"body":"This can be very frustrating"},{"startTime":87.8,"endTime":91.47,"body":"to patients who experience it."},{"startTime":91.47,"endTime":93.17,"body":"[Dr. Wiener] Okay. Let's get"},{"startTime":91.47,"endTime":93.17,"body":"back to your initial thought"},{"startTime":93.17,"endTime":95.72,"body":"because our clinicians"},{"startTime":93.17,"endTime":95.72,"body":"were thinking the same."},{"startTime":95.72,"endTime":99.118,"body":"An emergent non-contrast"},{"startTime":95.72,"endTime":99.118,"body":"head CT showed no evidence"},{"startTime":99.118,"endTime":101.35,"body":"of intracranial hemorrhage or edema"},{"startTime":101.35,"endTime":103.87,"body":"but there was only mild"},{"startTime":101.35,"endTime":103.87,"body":"loss of gray-white matter"},{"startTime":103.87,"endTime":105.97,"body":"differentiation diffusely."},{"startTime":105.97,"endTime":107.97,"body":"So the team is thinking of administering"},{"startTime":107.97,"endTime":110.862,"body":"intravenous recombinant"},{"startTime":107.97,"endTime":110.862,"body":"tissue plasminogen activator"},{"startTime":110.862,"endTime":113.0,"body":"or tPA for this patient."},{"startTime":113.0,"endTime":114.986,"body":"[Dr. Handy] Yeah, I would"},{"startTime":113.0,"endTime":114.986,"body":"agree with that assessment."},{"startTime":114.986,"endTime":118.64,"body":"The National Institute of"},{"startTime":114.986,"endTime":118.64,"body":"Neurological Disorders and Stroke"},{"startTime":118.64,"endTime":122.43,"body":"or NINDS had a study,"},{"startTime":118.64,"endTime":122.43,"body":"the rtPA stroke study"},{"startTime":122.43,"endTime":125.05,"body":"that showed a clear benefit for IV tPA"},{"startTime":125.05,"endTime":127.61,"body":"in selected patients with acute stroke."},{"startTime":127.61,"endTime":131.35,"body":"This study used IV tPA versus"},{"startTime":127.61,"endTime":131.35,"body":"placebo in ischemic stroke"},{"startTime":131.35,"endTime":134.04,"body":"within 3 hours of onset of symptoms."},{"startTime":134.04,"endTime":137.02,"body":"One half of the patients were"},{"startTime":134.04,"endTime":137.02,"body":"treated within 90 minutes"},{"startTime":137.02,"endTime":139.41,"body":"and symptomatic intracranial"},{"startTime":137.02,"endTime":139.41,"body":"hemorrhage occurred"},{"startTime":139.41,"endTime":142.518,"body":"in 6.4% of patients on the tPA arm"},{"startTime":142.518,"endTime":145.293,"body":"and 0.6% on placebo."},{"startTime":145.293,"endTime":146.38,"body":"In the tPA group,"},{"startTime":146.38,"endTime":149.27,"body":"there was a significant"},{"startTime":146.38,"endTime":149.27,"body":"12% absolute increase"},{"startTime":149.27,"endTime":152.61,"body":"in the number of patients who"},{"startTime":149.27,"endTime":152.61,"body":"only had minimal disability."},{"startTime":152.61,"endTime":153.93,"body":"[Dr. Wiener] Okay."},{"startTime":152.61,"endTime":153.93,"body":"That's pretty impressive."},{"startTime":153.93,"endTime":155.69,"body":"But what about mortality and morbidity?"},{"startTime":155.69,"endTime":158.6,"body":"You mentioned a much higher"},{"startTime":155.69,"endTime":158.6,"body":"risk of intracranial hemorrhage."},{"startTime":158.6,"endTime":160.487,"body":"[Dr. Handy] In that study,"},{"startTime":158.6,"endTime":160.487,"body":"there was a non-significant"},{"startTime":160.487,"endTime":163.71,"body":"4% reduction in mortality"},{"startTime":160.487,"endTime":163.71,"body":"in the tPA group."},{"startTime":163.71,"endTime":165.7,"body":"So despite an increased incidence"},{"startTime":165.7,"endTime":167.87,"body":"of symptomatic intracranial hemorrhage,"},{"startTime":167.87,"endTime":171.02,"body":"treatment with IV tPA"},{"startTime":167.87,"endTime":171.02,"body":"within 3 hours of the onset"},{"startTime":171.02,"endTime":174.5,"body":"of ischemic stroke, overall"},{"startTime":171.02,"endTime":174.5,"body":"improves clinical outcomes."},{"startTime":174.5,"endTime":176.14,"body":"[Dr. Wiener] Okay. But"},{"startTime":174.5,"endTime":176.14,"body":"is that the final answer?"},{"startTime":176.14,"endTime":178.455,"body":"What about things like age and timing?"},{"startTime":178.455,"endTime":180.66,"body":"[Dr. Handy] Yes, so it does"},{"startTime":178.455,"endTime":180.66,"body":"get a bit more complicated."},{"startTime":180.66,"endTime":184.07,"body":"So three subsequent trials"},{"startTime":180.66,"endTime":184.07,"body":"of IV tPA did not confirm"},{"startTime":184.07,"endTime":186.05,"body":"the benefits of that initial study,"},{"startTime":186.05,"endTime":188.33,"body":"perhaps because of the dose of tPA used"},{"startTime":188.33,"endTime":189.83,"body":"or the timing of its delivery"},{"startTime":189.83,"endTime":192.61,"body":"and then variations in the sample size."},{"startTime":192.61,"endTime":195.48,"body":"When data from all"},{"startTime":192.61,"endTime":195.48,"body":"randomized IV tPA trials"},{"startTime":195.48,"endTime":198.18,"body":"were combined however,"},{"startTime":195.48,"endTime":198.18,"body":"efficacy was confirmed"},{"startTime":198.18,"endTime":200.43,"body":"in the less than 3 hour time window"},{"startTime":200.43,"endTime":203.2,"body":"and the efficacy likely extended to 4.5"},{"startTime":203.2,"endTime":205.43,"body":"and possibly even 6 hours."},{"startTime":205.43,"endTime":207.08,"body":"Based on these combined results,"},{"startTime":207.08,"endTime":211.37,"body":"the ECASS III study explored"},{"startTime":207.08,"endTime":211.37,"body":"the safety and efficacy of tPA"},{"startTime":211.37,"endTime":214.099,"body":"in the 3 to 4.5 hour time window."},{"startTime":214.099,"endTime":215.662,"body":"[Dr. Wiener] And what did that study show?"},{"startTime":215.662,"endTime":217.723,"body":"[Dr. Handy] Unlike the"},{"startTime":215.662,"endTime":217.723,"body":"original NINDS study that"},{"startTime":217.723,"endTime":220.74,"body":"I mentioned, patients who"},{"startTime":217.723,"endTime":220.74,"body":"were over the age of 80"},{"startTime":220.74,"endTime":224.11,"body":"and diabetic patients with a"},{"startTime":220.74,"endTime":224.11,"body":"previous stroke were excluded."},{"startTime":224.11,"endTime":226.87,"body":"In this 821 patient randomized study,"},{"startTime":226.87,"endTime":228.8,"body":"efficacy was again confirmed,"},{"startTime":228.8,"endTime":231.04,"body":"although the treatment"},{"startTime":228.8,"endTime":231.04,"body":"effect was less robust"},{"startTime":231.04,"endTime":235.002,"body":"beyond 3 hours than in the"},{"startTime":231.04,"endTime":235.002,"body":"0 to 3 hour time window."},{"startTime":235.002,"endTime":236.03,"body":"In the tPA group,"},{"startTime":236.03,"endTime":239.36,"body":"52% of patients achieved"},{"startTime":236.03,"endTime":239.36,"body":"a good outcome at 90 days,"},{"startTime":239.36,"endTime":241.888,"body":"and that's in comparison"},{"startTime":239.36,"endTime":241.888,"body":"to 45% of patients"},{"startTime":241.888,"endTime":243.56,"body":"in the placebo group."},{"startTime":243.56,"endTime":245.62,"body":"The symptomatic"},{"startTime":243.56,"endTime":245.62,"body":"intracranial hemorrhage rate"},{"startTime":245.62,"endTime":247.934,"body":"was 2.4% in the tPA group"},{"startTime":247.934,"endTime":250.775,"body":"and 0.2% in the placebo group."},{"startTime":250.775,"endTime":253.43,"body":"So based on these data, tPA is approved"},{"startTime":253.43,"endTime":255.81,"body":"in the 3 to 4.5 hour time window"},{"startTime":255.81,"endTime":258.112,"body":"in Europe and Canada but"},{"startTime":255.81,"endTime":258.112,"body":"it's still only approved"},{"startTime":258.112,"endTime":260.76,"body":"for 0 to 3 hours in the United States."},{"startTime":260.76,"endTime":262.44,"body":"[Dr. Wiener] Wow. That's"},{"startTime":260.76,"endTime":262.44,"body":"pretty complicated."},{"startTime":262.44,"endTime":264.51,"body":"But at the end of the"},{"startTime":262.44,"endTime":264.51,"body":"day, would you give tPA"},{"startTime":264.51,"endTime":265.5,"body":"to this patient?"},{"startTime":265.5,"endTime":267.12,"body":"[Dr. Handy] I first need to"},{"startTime":265.5,"endTime":267.12,"body":"make sure he doesn't have"},{"startTime":267.12,"endTime":269.59,"body":"any contraindications to using the drug."},{"startTime":269.59,"endTime":271.52,"body":"So can you tell me more about that?"},{"startTime":271.52,"endTime":273.53,"body":"[Dr. Wiener] Yeah, so the"},{"startTime":271.52,"endTime":273.53,"body":"patient's initial blood pressure"},{"startTime":273.53,"endTime":276.68,"body":"on presentation in the"},{"startTime":273.53,"endTime":276.68,"body":"emergency room is 220/140"},{"startTime":276.68,"endTime":279.61,"body":"and despite treatment"},{"startTime":276.68,"endTime":279.61,"body":"with IV antihypertensive"},{"startTime":279.61,"endTime":282.5,"body":"remains at 195/120."},{"startTime":282.5,"endTime":284.87,"body":"On further review of the"},{"startTime":282.5,"endTime":284.87,"body":"patient's medical history,"},{"startTime":284.87,"endTime":287.13,"body":"he has had a prior"},{"startTime":284.87,"endTime":287.13,"body":"embolic stroke affecting"},{"startTime":287.13,"endTime":290.1,"body":"the posterior circulation 12 months ago."},{"startTime":290.1,"endTime":292.11,"body":"He also has a history"},{"startTime":290.1,"endTime":292.11,"body":"of colon cancer that was"},{"startTime":292.11,"endTime":293.71,"body":"diagnosed three months ago"},{"startTime":293.71,"endTime":295.4,"body":"when he presented with a lower GI bleed"},{"startTime":295.4,"endTime":297.23,"body":"that required a transfusion."},{"startTime":297.23,"endTime":300.11,"body":"He successfully underwent"},{"startTime":297.23,"endTime":300.11,"body":"a left hemicolectomy"},{"startTime":300.11,"endTime":302.58,"body":"of a stage 1 adenocarcinoma"},{"startTime":302.58,"endTime":304.66,"body":"approximately three months ago."},{"startTime":304.66,"endTime":306.54,"body":"[Dr. Handy] Okay. So there's"},{"startTime":304.66,"endTime":306.54,"body":"a lot of information here"},{"startTime":306.54,"endTime":308.68,"body":"and this isn't going to"},{"startTime":306.54,"endTime":308.68,"body":"be a simple decision."},{"startTime":308.68,"endTime":310.16,"body":"[Dr. Wiener] Okay. Let's get"},{"startTime":308.68,"endTime":310.16,"body":"onto the question because"},{"startTime":310.16,"endTime":312.69,"body":"I think it's going to delve"},{"startTime":310.16,"endTime":312.69,"body":"into some of these matters."},{"startTime":312.69,"endTime":315.44,"body":"The question asks, which"},{"startTime":312.69,"endTime":315.44,"body":"of the following factors"},{"startTime":315.44,"endTime":320.4,"body":"is a contraindication to the"},{"startTime":315.44,"endTime":320.4,"body":"use of IV tPA in this patient?"},{"startTime":320.4,"endTime":324.64,"body":"And the options are A."},{"startTime":320.4,"endTime":324.64,"body":"age greater than 65;"},{"startTime":324.64,"endTime":328.62,"body":"B. blood pressure greater than 185/110;"},{"startTime":328.62,"endTime":332.79,"body":"C. gastrointestinal bleed"},{"startTime":328.62,"endTime":332.79,"body":"within the past three months;"},{"startTime":332.79,"endTime":336.27,"body":"D. major surgery within"},{"startTime":332.79,"endTime":336.27,"body":"the past three months;"},{"startTime":336.27,"endTime":338.98,"body":"E. a prior embolic stroke;"},{"startTime":338.98,"endTime":342.064,"body":"or F. none of these is a contraindication."},{"startTime":342.064,"endTime":343.93,"body":"[Dr. Handy] Well, let me go"},{"startTime":342.064,"endTime":343.93,"body":"over the contraindications"},{"startTime":343.93,"endTime":345.82,"body":"for tPA administration."},{"startTime":345.82,"endTime":350.18,"body":"So they are a sustained"},{"startTime":345.82,"endTime":350.18,"body":"blood pressure over 185/110"},{"startTime":350.18,"endTime":353.43,"body":"despite treatment, a bleeding diathesis,"},{"startTime":353.43,"endTime":356.65,"body":"a recent head injury or"},{"startTime":353.43,"endTime":356.65,"body":"intracerebral hemorrhage,"},{"startTime":356.65,"endTime":359.98,"body":"major surgery in the preceding 14 days,"},{"startTime":359.98,"endTime":363.03,"body":"gastrointestinal bleeding"},{"startTime":359.98,"endTime":363.03,"body":"in the preceding 21 days,"},{"startTime":363.03,"endTime":365.6,"body":"or a recent myocardial infarction."},{"startTime":365.6,"endTime":366.59,"body":"So for this patient,"},{"startTime":366.59,"endTime":369.66,"body":"he does have sustained"},{"startTime":366.59,"endTime":369.66,"body":"hypertension despite treatment,"},{"startTime":369.66,"endTime":373.16,"body":"so that would be the contraindication"},{"startTime":369.66,"endTime":373.16,"body":"to administering tPA,"},{"startTime":373.16,"endTime":375.047,"body":"and that would make the answer B."},{"startTime":375.047,"endTime":376.86,"body":"[Dr. Wiener] And for"},{"startTime":375.047,"endTime":376.86,"body":"the rest of the options?"},{"startTime":376.86,"endTime":378.24,"body":"[Dr. Handy] Well, the other"},{"startTime":376.86,"endTime":378.24,"body":"major thing that came up"},{"startTime":378.24,"endTime":380.19,"body":"in his past history is his GI bleed"},{"startTime":380.19,"endTime":382.69,"body":"in the setting of a colon"},{"startTime":380.19,"endTime":382.69,"body":"cancer three months ago,"},{"startTime":382.69,"endTime":384.54,"body":"but that's outside of the time period"},{"startTime":384.54,"endTime":387.53,"body":"that would be considered"},{"startTime":384.54,"endTime":387.53,"body":"a contraindication for tPA"},{"startTime":387.53,"endTime":389.62,"body":"and he's had successful surgery."},{"startTime":389.62,"endTime":391.75,"body":"The prior embolic CVA that he's had"},{"startTime":391.75,"endTime":393.73,"body":"is not a contraindication."},{"startTime":393.73,"endTime":395.345,"body":"[Dr. Wiener] And I'm"},{"startTime":393.73,"endTime":395.345,"body":"assuming that the persistent"},{"startTime":395.345,"endTime":397.64,"body":"hypertension, the"},{"startTime":395.345,"endTime":397.64,"body":"contraindication there is because"},{"startTime":397.64,"endTime":399.67,"body":"it increases your risk of"},{"startTime":397.64,"endTime":399.67,"body":"intracerebral hemorrhage?"},{"startTime":399.67,"endTime":401.06,"body":"[Dr. Handy] Yes, that's right."},{"startTime":401.06,"endTime":402.785,"body":"[Dr. Wiener] Okay. Well"},{"startTime":401.06,"endTime":402.785,"body":"while we're talking about"},{"startTime":402.785,"endTime":405.43,"body":"ischemic stroke, let's"},{"startTime":402.785,"endTime":405.43,"body":"continue to discuss treatment."},{"startTime":405.43,"endTime":407.34,"body":"This is a two-part question."},{"startTime":407.34,"endTime":410.2,"body":"This patient did not get tPA"},{"startTime":407.34,"endTime":410.2,"body":"because of his hypertension,"},{"startTime":410.2,"endTime":411.81,"body":"as you articulated."},{"startTime":411.81,"endTime":414.22,"body":"The next question asks,"},{"startTime":411.81,"endTime":414.22,"body":"which of the following"},{"startTime":414.22,"endTime":416.93,"body":"antiplatelet agents has"},{"startTime":414.22,"endTime":416.93,"body":"been proven effective"},{"startTime":416.93,"endTime":419.86,"body":"in the acute treatment of ischemic stroke?"},{"startTime":419.86,"endTime":422.585,"body":"And the options are A. aspirin;"},{"startTime":422.585,"endTime":424.68,"body":"B. clopidogrel;"},{"startTime":424.68,"endTime":426.95,"body":"C. dipyridamole;"},{"startTime":426.95,"endTime":429.381,"body":"D. prasugrel;"},{"startTime":429.381,"endTime":431.773,"body":"or E. ticagrelor."},{"startTime":431.773,"endTime":434.47,"body":"[Dr. Handy] So aspirin is"},{"startTime":431.773,"endTime":434.47,"body":"the only antiplatelet agent"},{"startTime":434.47,"endTime":436.71,"body":"that has been proven"},{"startTime":434.47,"endTime":436.71,"body":"effective for the treatment"},{"startTime":436.71,"endTime":439.03,"body":"of acute ischemic stroke."},{"startTime":439.03,"endTime":442.76,"body":"Two large trials, the"},{"startTime":439.03,"endTime":442.76,"body":"IST and the CAST trial"},{"startTime":442.76,"endTime":445.41,"body":"found that the use of"},{"startTime":442.76,"endTime":445.41,"body":"aspirin within 48 hours"},{"startTime":445.41,"endTime":448.57,"body":"of stroke onset reduced"},{"startTime":445.41,"endTime":448.57,"body":"both stroke recurrence risk"},{"startTime":448.57,"endTime":450.5,"body":"and mortality minimally."},{"startTime":450.5,"endTime":452.61,"body":"So in the first study, the IST trial,"},{"startTime":452.61,"endTime":456.45,"body":"there were 19,435 patients."},{"startTime":456.45,"endTime":459.58,"body":"Those allocated to aspirin 300 mg per day"},{"startTime":459.58,"endTime":462.56,"body":"had slightly fewer deaths within 14 days,"},{"startTime":462.56,"endTime":465.66,"body":"significantly fewer"},{"startTime":462.56,"endTime":465.66,"body":"recurrent ischemic strokes,"},{"startTime":465.66,"endTime":468.15,"body":"no excess risk of hemorrhagic strokes,"},{"startTime":468.15,"endTime":470.11,"body":"and a trend towards a reduction in death"},{"startTime":470.11,"endTime":472.48,"body":"or dependence at six months."},{"startTime":472.48,"endTime":476.69,"body":"In the CAST trial, 21,106"},{"startTime":472.48,"endTime":476.69,"body":"patients with ischemic stroke"},{"startTime":476.69,"endTime":480.33,"body":"received 160 mg per day"},{"startTime":476.69,"endTime":480.33,"body":"of aspirin or a placebo"},{"startTime":480.33,"endTime":482.04,"body":"for up to four weeks."},{"startTime":482.04,"endTime":484.56,"body":"There were very small"},{"startTime":482.04,"endTime":484.56,"body":"reductions in the aspirin group"},{"startTime":484.56,"endTime":487.42,"body":"in early mortality,"},{"startTime":484.56,"endTime":487.42,"body":"recurrent ischemic strokes"},{"startTime":487.42,"endTime":490.21,"body":"and dependency at discharge or death."},{"startTime":490.21,"endTime":492.39,"body":"These trials demonstrate"},{"startTime":490.21,"endTime":492.39,"body":"that the use of aspirin"},{"startTime":492.39,"endTime":494.36,"body":"in the treatment of acute ischemic stroke"},{"startTime":494.36,"endTime":497.38,"body":"is safe and produces a small net benefit."},{"startTime":497.38,"endTime":500.16,"body":"For every 1,000 acute"},{"startTime":497.38,"endTime":500.16,"body":"strokes treated with aspirin,"},{"startTime":500.16,"endTime":502.94,"body":"about nine deaths or"},{"startTime":500.16,"endTime":502.94,"body":"non-fatal stroke recurrences"},{"startTime":502.94,"endTime":505.15,"body":"will be prevented in the first few weeks,"},{"startTime":505.15,"endTime":507.37,"body":"and about 13 fewer patients will be dead"},{"startTime":507.37,"endTime":509.21,"body":"or dependent at six months."},{"startTime":509.21,"endTime":510.696,"body":"[Dr. Wiener] So it's"},{"startTime":509.21,"endTime":510.696,"body":"important to distinguish that"},{"startTime":510.696,"endTime":513.33,"body":"these trials were really"},{"startTime":510.696,"endTime":513.33,"body":"only in acute strokes."},{"startTime":513.33,"endTime":516.13,"body":"This has nothing to do with"},{"startTime":513.33,"endTime":516.13,"body":"secondary prevention of stroke."},{"startTime":516.13,"endTime":517.677,"body":"[Dr. Handy] That's exactly right."},{"startTime":517.677,"endTime":519.95,"body":"[Dr. Wiener] And the effects"},{"startTime":517.677,"endTime":519.95,"body":"of the aspirin were not nearly"},{"startTime":519.95,"endTime":522.53,"body":"the size of effects you're"},{"startTime":519.95,"endTime":522.53,"body":"talking about in the tPA."},{"startTime":522.53,"endTime":524.24,"body":"Are there any other agents"},{"startTime":522.53,"endTime":524.24,"body":"that are used at all"},{"startTime":524.24,"endTime":526.09,"body":"for patients who've had strokes?"},{"startTime":526.09,"endTime":528.381,"body":"[Dr. Handy] The short term"},{"startTime":526.09,"endTime":528.381,"body":"combination of clopidogrel"},{"startTime":528.381,"endTime":531.52,"body":"with aspirin may be effective"},{"startTime":528.381,"endTime":531.52,"body":"in preventing second stroke,"},{"startTime":531.52,"endTime":533.8,"body":"but a number of trials"},{"startTime":531.52,"endTime":533.8,"body":"did not show a benefit"},{"startTime":533.8,"endTime":536.09,"body":"of clopidogrel in combination with aspirin"},{"startTime":536.09,"endTime":538.25,"body":"for the treatment of acute stroke."},{"startTime":538.25,"endTime":541.63,"body":"A trial of over 5,000"},{"startTime":538.25,"endTime":541.63,"body":"Chinese patients enrolled"},{"startTime":541.63,"endTime":544.84,"body":"within 24 hours of TIA"},{"startTime":541.63,"endTime":544.84,"body":"or minor ischemic stroke"},{"startTime":544.84,"endTime":547.67,"body":"found that the clopidogrel-aspirin regimen"},{"startTime":547.67,"endTime":549.7,"body":"was superior to aspirin alone"},{"startTime":549.7,"endTime":554.04,"body":"with the 90 day stroke risk"},{"startTime":549.7,"endTime":554.04,"body":"decreased from 11 to 8%"},{"startTime":554.04,"endTime":556.25,"body":"and no increase in major hemorrhage."},{"startTime":556.25,"endTime":558.47,"body":"This benefit was limited"},{"startTime":556.25,"endTime":558.47,"body":"to those not carrying"},{"startTime":558.47,"endTime":561.42,"body":"the CYP2C19 polymorphism associated"},{"startTime":561.42,"endTime":563.98,"body":"with clopidogrel hypometabolism."},{"startTime":563.98,"endTime":566.8,"body":"A similar trial of short"},{"startTime":563.98,"endTime":566.8,"body":"term use of the combination"},{"startTime":566.8,"endTime":569.05,"body":"of ticagrelor and aspirin in patients"},{"startTime":569.05,"endTime":572.33,"body":"with mild non-cardioembolic stroke or TIA"},{"startTime":572.33,"endTime":574.42,"body":"showed the risk of"},{"startTime":572.33,"endTime":574.42,"body":"recurrent stroke or death"},{"startTime":574.42,"endTime":576.96,"body":"within 30 days was"},{"startTime":574.42,"endTime":576.96,"body":"significantly lower than"},{"startTime":576.96,"endTime":579.18,"body":"with aspirin alone,"},{"startTime":576.96,"endTime":579.18,"body":"making this combination"},{"startTime":579.18,"endTime":581.77,"body":"an option for those"},{"startTime":579.18,"endTime":581.77,"body":"patients who do not tolerate"},{"startTime":581.77,"endTime":584.688,"body":"or are resistant to the"},{"startTime":581.77,"endTime":584.688,"body":"effects of clopidogrel."},{"startTime":584.688,"endTime":586.69,"body":"[Dr. Wiener] And what about dipyridamole?"},{"startTime":586.69,"endTime":588.673,"body":"[Dr. Handy] So that's"},{"startTime":586.69,"endTime":588.673,"body":"erratically absorbed depending on"},{"startTime":588.673,"endTime":592.56,"body":"stomach pH but a newer"},{"startTime":588.673,"endTime":592.56,"body":"formulation combines timed release"},{"startTime":592.56,"endTime":594.53,"body":"dipyridamole with aspirin"},{"startTime":594.53,"endTime":597.21,"body":"and has better oral bioavailability."},{"startTime":597.21,"endTime":600.57,"body":"The ESPS-2 study showed"},{"startTime":597.21,"endTime":600.57,"body":"efficacy of both drugs"},{"startTime":600.57,"endTime":602.74,"body":"in preventing stroke and a significantly"},{"startTime":602.74,"endTime":606.07,"body":"better risk reduction when"},{"startTime":602.74,"endTime":606.07,"body":"the two agents were combined."},{"startTime":606.07,"endTime":610.4,"body":"The open-label ESPRIT trial"},{"startTime":606.07,"endTime":610.4,"body":"confirmed the ESPS-2 results."},{"startTime":610.4,"endTime":612.28,"body":"After three and a half years of follow-up,"},{"startTime":612.28,"endTime":615.82,"body":"13% of patients on"},{"startTime":612.28,"endTime":615.82,"body":"aspirin and dipyridamole"},{"startTime":615.82,"endTime":618.5,"body":"and 16% of patients on aspirin alone"},{"startTime":618.5,"endTime":621.89,"body":"met the primary outcome of"},{"startTime":618.5,"endTime":621.89,"body":"death from all vascular causes."},{"startTime":621.89,"endTime":625.15,"body":"So the combination is approved"},{"startTime":621.89,"endTime":625.15,"body":"for the prevention of stroke."},{"startTime":625.15,"endTime":627.24,"body":"[Dr. Wiener] And why"},{"startTime":625.15,"endTime":627.24,"body":"don't you use prasugrel?"},{"startTime":627.24,"endTime":629.19,"body":"[Dr. Handy] There's a black"},{"startTime":627.24,"endTime":629.19,"body":"box warning on prasugrel"},{"startTime":629.19,"endTime":632.32,"body":"to not use it in patients with"},{"startTime":629.19,"endTime":632.32,"body":"a history of TIA or stroke."},{"startTime":632.32,"endTime":634.41,"body":"So that would not be indicated here."},{"startTime":634.41,"endTime":636.34,"body":"That comes from a post hoc analysis"},{"startTime":636.34,"endTime":638.49,"body":"of the TRITON-TIMI 38 data,"},{"startTime":638.49,"endTime":640.54,"body":"where there was not a"},{"startTime":638.49,"endTime":640.54,"body":"benefit, and even a harm"},{"startTime":640.54,"endTime":642.11,"body":"to giving prasugrel in patients"},{"startTime":642.11,"endTime":644.1,"body":"with a history of stroke or TIA."},{"startTime":644.1,"endTime":646.53,"body":"So it's not used in that scenario."},{"startTime":646.53,"endTime":648.85,"body":"[Dr. Wiener] Okay. So"},{"startTime":646.53,"endTime":648.85,"body":"the teaching points here"},{"startTime":648.85,"endTime":651.67,"body":"are that in a patient with"},{"startTime":648.85,"endTime":651.67,"body":"an acute ischemic stroke"},{"startTime":651.67,"endTime":653.6,"body":"generally less than 4.5 hours"},{"startTime":653.6,"endTime":656.12,"body":"an intravenous infusion"},{"startTime":653.6,"endTime":656.12,"body":"of tPA is beneficial"},{"startTime":656.12,"endTime":659.15,"body":"in terms of morbidity"},{"startTime":656.12,"endTime":659.15,"body":"and recovered function."},{"startTime":659.15,"endTime":661.72,"body":"In patients with a"},{"startTime":659.15,"endTime":661.72,"body":"contraindication to tPA,"},{"startTime":661.72,"endTime":664.7,"body":"aspirin, possibly combined"},{"startTime":661.72,"endTime":664.7,"body":"with another antiplatelet"},{"startTime":664.7,"endTime":667.21,"body":"medication may also improve outcomes,"},{"startTime":667.21,"endTime":670.5,"body":"although the magnitude of the"},{"startTime":667.21,"endTime":670.5,"body":"improvement is not nearly that"},{"startTime":670.5,"endTime":672.51,"body":"to the degree of tPA."},{"startTime":672.51,"endTime":674.04,"body":"[Dr. Handy] And if you want"},{"startTime":672.51,"endTime":674.04,"body":"to learn more about this,"},{"startTime":674.04,"endTime":675.83,"body":"you can check out the Harrison's chapter"},{"startTime":675.83,"endTime":677.051,"body":"on ischemic stroke."},{"startTime":677.051,"endTime":680.24,"body":"[outro music]"},{"startTime":681.49,"endTime":684.36,"body":"[Mr. Shanahan] This is Jim"},{"startTime":681.49,"endTime":684.36,"body":"Shanahan, publisher at McGraw Hill."},{"startTime":684.36,"endTime":685.97,"body":"Harrison's Podclass is brought to you"},{"startTime":685.97,"endTime":687.94,"body":"by McGraw Hill's Access Medicine,"},{"startTime":687.94,"endTime":690.06,"body":"the online medical resource that delivers"},{"startTime":690.06,"endTime":693.27,"body":"the latest trusted content from"},{"startTime":690.06,"endTime":693.27,"body":"the best minds in medicine."},{"startTime":693.27,"endTime":695.823,"body":"Go to accessmedicine.com to learn more."}]}