Thread by @cardiomet_CE

Watch here TOMORROW for a new accredited, #tweetorial by neurointensivist @stephanamayer on optimizing DAPT and other interventions for secondary stroke prevention after #AIS or #TIA. Earn 0.5 CE/#CME credits: #physicians, #nurses, #pharmacists! #NoMercyOnStroke @svinsociety

@WorldStrokeCampaign @American_Stroke @WorldStrokeOrg @neurocriticalcare
@MainaliShradda @vcurrutiaMD @almuftifawaz @drdangayach @AlexChebl @GhadaMohamedMD @AmeerEHassan @aartisarwal @sheth_kevin @MitchElkind #medtwitter @academiccme #neurotwitter #FOAMed #FOAM #stroketwitter

1) Welcome to a #tweetorial on how to optimize therapy for secondary #stroke prevention. Accredited for 0.50 credits! I am your host @stephanamayer. Be sure to see prior tweetorials in the broader cardiometabolic space and earn more CE/#CME credit at cardiometabolic-ce.com

2) This series is supported by educational grants from AstraZeneca, Bayer, and Chiesi, and is intended for healthcare providers. Faculty disclosures are listed at cardiometabolic-ce.com/disclosures/.

3) Why focus on secondary stroke prevention? Because it is probably the single most important decision you make when discharging a patient who has experienced a stroke. Approximately 23% of strokes are recurrent, and minor strokes often lead to major ones.

4) In one study the 10-year risk of stroke or MI after an initial TIA was 44%!

webmd.com/stroke/news/20…

5) The best current evidence for preventing recurrent stroke comes from the 2021 AHA/ASA Guidelines for Secondary Stroke Prevention. The top 10 take home messages are summarized here:

ahajournals.org/doi/10.1161/ST…

6) Now let's start with a case!

7) Case summary: A 65 y/o woman with history of hypertension, DM2 and hyperlipidemia presents upon awakening with R face and arm weakness and dysarthria. NIHSS score is 3. BP is 185/113 mm Hg, HR is 87 and regular. Glucose is 194 mg/dl. NCCT of the brain is normal.

8) CTA of the head and neck is negative for LVO or cervical ICA stenosis, but the left mid-M1 segment shows moderate focal stenosis c/w ICAD. An MRI has been ordered.

9) Q1: Regarding her diagnostic work-up, which of the following should be completed within the next 48 hours?

10) Here’s the MR.

Q2: Based on her work-up so far, what is the most likely cause of her stroke?
a) Cardioembolism / ESUS
b) Carotid stenosis
c) Small penetrating artery vessel occlusion
d) Arterial dissection

11) Q3: The ECHO shows LVH with no visualized thrombus. Telemetry shows no evidence of A Fib. Her HbA1C is 9.2 %, and her LDL is 120 md/dl. Which of the following goals of therapy is accurate according to the AHA/ASA Guidelines? (P.S. the others are inaccurate)

(Q3)
a) Target BP to <140/90
b) Target HbA1C to <8%
c) Target LDL-C to <70 mg/dl
d) Refrain from any alcohol consumption

12) Q4: Her current medications include aspirin 81 mg daily, atorvastatin 40 mg daily, lisinopril 20 mg daily, and hydrochlorothiazide 25 mg daily. What would be the LEAST reasonable long-term treatment option?

(Q4)
a) Increase the ASA to 325 mg qd
b) Cont ASA 81 mg qd and add clopidogrel 75 mg QD
c) Cont the ASA 81 mg qd and add ticagrelor 90 mg QD
d) Cont ASA 81 mg qd and add apixaban 5 mg BID

13) OK that’s it for today! Come back tomorrow for Part 2 of this tweetorial on Optimizing Secondary Stroke Prevention to learn the answers to questions 1-4! #FOAMed @MedTweetorials #neurotwitter #stroke

14) Welcome back! I am @stephanamayer – denizen of neurocritical care and stroke – and we are back to discuss strategies for optimizing secondary stroke prevention.

15) You have found the web's ONLY source of accredited tweetorials in #cardiometabolic medicine. Welcome #physicians, #nurses, #pharmacists! Welcome #PAs & #NPs! @AshuPJadhav @GreenJournal @guroledip @Ivobach @johanna_ospel @NguyenThanhMD @elghanemmoh @FrontNeurosci @FrontNeurol

16) To recap, you just admitted a 65 y/o F with HTN, DM2, and HL. She has a right pure motor stroke with NIHSS=3 for face + arm weakness and dysarthria. Yesterday's polls? The correct answer to Q1 is d) All of the above.

17) The 2021 AHA/ASA guidelines recommend that ECHO, cardiac monitoring, HbA1C & lipid profile testing all be performed after AIS w/in 48h of admission. But wait! Weren’t we told that lipid panels are inaccurate right after a stroke & that testing should be delayed by 12 weeks?

18) One small study (N=38) made that assertion (Yan B et al, Cerebrovasc Dis 2005;19:234); in some patients total chol was even HIGHER 12w later. So diagnosing high chol or LDL-C levels acutely after stroke is meaningful & warrants immed intervention w/hi-dose statin therapy.

19) Re Q2: What is the most likely cause (or mechanism) of her stroke?
The correct answer is C, small penetrating artery vessel occlusion. The MRI scan shows a classic deep, punctate left basal ganglia infarct. These so-called “lacunar” strokes are caused not by emboli ...

20) ... but by local atherothrombosis that occurs in diseased arterial segments. Platelet-vessel interactions play a huge role in the pathogenesis of these strokes. Hence the main weapon to prevent stroke recurrence from this mechanism is antiplatelet therapy.

21) Let’s review Q3: Which of the following goals of therapy is accurate according to AHA/ASA Guidelines? (P.S. the others are inaccurate)
a) Target BP to <140/90
b) Target HbA1C to <8%
c) Target LDL-C to <70 mg/dl
d) Refrain from any alcohol consumption
The correct answer ...

22) ... is C: Target LDL-C to <70 mg/dl. Why is that? The suggested target BP is <130/70 mm Hg. Target HbA1C is <7%. The recommendation for moderate physical activity for only 10 mins 4x/week.

23) Finally, there is no blanket restriction against all forms of alcohol consumption in the AHA/ASA guidelines. The warning is to refrain from heavy consumption, because it ⬆️ the risk of hemorrhagic stroke. So an occasional glass of wine is probably OK.

Viva la France!

24) Now the answer to Q4: Your patient had a mild completed pure motor stroke with an NIHSS score of 3 on ASA 81 mg daily. What would be the LEAST reasonable long-term treatment option? The answer is D) Cont ASA 81 mg qd and add apixaban 5 mg BID.

25) If fact, there is no effective indication for any combination of anticoagulation and antiplatelet therapy for the prevention of stroke. The risk of bleeding is just too high.

26) The other options: increasing the ASA dose or adding clopidogrel or ticagrelor to ASA for 1-3 mo, are all reasonable. So would be switching to an ASA-dipyridamole combination pill. But--some of these options might be better than others. What do the clinical trials tell us?

27) The two big stroke secondary prevention trials that put dual antiplatelet therapy (#DAPT) on the map were CHANCE (Wang et al, NEJM 2013;369:11) & POINT (Johnston et al, NEJM 2016;375:35). Both est'd that a limited course of clopidogrel added to ASA after minor stroke/TIA ...

28) ... can reduce the risk of recurrent stroke. CHANCE randomized > 5,000 pts with minor stroke or high risk TIA w/in 24h of the index event. The active treatment group received clopidogrel + ASA for 21d, vs ASA alone.

29) The result? More stroke free survival at 90d with DAPT. A 3.5% absolute increase in recurrent stroke with ASA monotherapy.

30) POINT randomized almost 5,000 patients with minor stroke or high risk TIA within 12h of the index event. The active treatment group received clopidogrel + ASA for 30d, vs ASA alone. The result?

31) Less acute ischemic stroke, #MI, or vascular death at 30d: a 1.5% absolute reduction in recurrent stroke with DAPT vs. ASA monotherapy.

32) So going back to our 65 y/o woman with a pure motor stroke and NIHSS of 3, loading with clopidogrel within 24 hours of onset and continuing DAPT for 30 days makes sense and is supported by the evidence. Are there any other alternatives to consider for DAPT?

33) Well, there’s #ticagrelor, an oral, reversible, direct-acting inhibitor of the ADP receptor P2Y12 that has a more rapid onset & ⬆️platelet inhibition than clopidogrel. #Clopidogrel is an irreversible P2Y12 blocker & is actually a prodrug. It needs to be metabolized ...

34) ... into the active form, which can take 2 hours or longer. So it doesn’t start working as fast as ticagrelor. In PLATO (Wallentin et al, NEJM 2009;361:1045) over 18,000 patients with #ACS w/ or w/o STEMI were randomized to ticagrelor vs clopidogrel + ASA.

35) Ticagrelor significantly reduced the rate of death from vascular causes, MI, or stroke (9.8% vs 11.7%) compared to clopidogrel, without an increase in major bleeding. So the cardiologists love ticagrelor.

36) In stroke, the best data for using ticagrelor for DAPT comes from the THALES trial. In this RCT > 11,000 minor stroke or high-risk TIA pts were randomized within 24h to ticagrelor+ASA vs ASA alone. The primary outcome of recurrent stroke or death at 30d occurred ...

37) ... in 5.4% with DAPT, vs 6.9% with ASA monotherapy.

38) Even more intriguing, in a prespecified subgroup analysis, events that localized to a >30% ipsilateral atherostenosis had a much higher recurrent stroke risk overall, and the treatment effect with ticagrelor was even greater: 7.9% vs 10.9%. The upshot?

39) Minor stroke or TIA associated with Intracranial atherosclerotic disease (#ICAD) or ipsilateral athero appears to be the optimal responder group for ticagrelor + ASA.

40) Back to our patient. She had a stroke involving right face and arm weakness and dysarthria, NIHSS score = 3. MRI showed a left BG lacunar infarct. CTA showed a left M1 stenosis corresponding to the location of the occluded vessel.

41) So there’s every reason to treat with DAPT for 30 days. Which combination of therapy would you use?

42) Please answer the poll and join us tomorrow for a wrap up! #FOAMed #NeuroTwitter @TheStrokeAssoc @StrokeAHA_ASA @AmerMalikMD @EladLevyMD @BarrowNeuro @AnneAlexandrov @VSainiMD @drltorres @walinjom @rajeroni @NAsdaghi

43) Welcome back! I am @stephanamayer and we are back to wrap up our #tweetorial on #DAPT in pts with #AIS or high risk #TIA. You have found the web's ONLY source of accredited tweetorials in #cardiometabolic medicine. Welcome #physicians, #nurses, #pharmacists!

44) Some final thoughts about the role of DAPT in secondary stroke prevention. A. The dose of ASA should not exceed 325 mg QD. Higher doses increase the bleeding risk without additional clinical benefit.

45) B. Loss of function polymorphisms in the CYP2c19 gene may impair the conversion of clopidogrel to the active metabolite, leading to reduced responsiveness to clopidogrel in up to 30% of patients. You might want to test for this.

46) Final thoughts. C. DAPT should generally not be used in patients with larger strokes (NIHSS >5) because of the increased risk of hemorrhagic infarction. D. There is no indication for continuing DAPT for >3 months for the secondary prevention of stroke.

47) The majority of the benefit from #DAPT occurs within the 1st week of treatment, whereas DAPT beyond 3 months of stroke onset increases risk without added benefit.

48) So you made it! Free CE/#CME! Special nods to #NoMercyOnStroke @WorldStrokeCampaign @American_Stroke @WorldStrokeOrg @svinsociety @neurocriticalcare @MainaliShradda @vcurrutiaMD @almuftifawaz @drdangayach @AlexChebl @GhadaMohamedMD @AmeerEHassan @aartisarwal @sheth_kevin

49) Now, #physicians, #pharmacists, #nurses: go to cardiometabolic-ce.com/plts11 and claim your credit! I am @stephanamayer. Follow @cardiomet_CE for more accredited tweetorials! #medtwittter #cardiotwitter @MedTweetorials @AAPAorg