1 Halker Singh Evaluation of Headaches MC Clinical Reviews 2024 CA R Secure

DIAGNOSIS, PREVENTION,
AND TREATMENT OF
HEADACHES
FOCUS ON MIGRAINE
Rashmi B. Halker Singh MD FAHS FAAN
Associate Professor of Neurology
Director, Headache Medicine Fellowship Program
Mayo Clinic
Scottsdale, AZ
Clinical Reviews 2024: 35th Annual Family Medicine and

Internal Medicine Update
February 21-24, 2024
©2021
©2021
MayoMayo
Foundation
Foundation
for Medical
for Medical
Education
Education
and Research
and Research
| WF57138-1
| slide-1
Advisory Board: Pfizer
Editorial services: Current Neurology and
Neuroscience Reports (Section editor/Headache);
Headache Journal (Deputy Editor, Online & Social
Disclosures Media Editor)
Board of Directors: American Headache Society (no
compensation)
Royalties: Oxford University Press
• Identify pearls to taking a good headache history
• Explore how to optimize acute migraine
treatment and manage medication overuse
Goals and headache
Objectives • Discuss key considerations to new migraine
therapies and how to choose between options
Deven is a 38-year-old high school teacher with severe headaches
Recalls headaches in college, would sometimes miss class
Recently pain is worse, over the counter medications aren’t helping
Describes pain as across the front of his head, starts dull and builds to
throbbing, nausea when severe
Part 1: Deven’s Bad Headaches Are Migraine

Distinguish Primary from Secondary
Headache Disorders
Red Flags in Headache: “SNOOP4”
Notes
S Systemic symptoms, signs, disease Fever, weight loss,
malignancy
N Neurologic symptoms, signs Papilledema, sensory,

motor, diplopia, bulbar
O Onset
m
Tensidad
xima
in en
X
Abrupt / thunderclap
minute
O Older New headache after age
0
Loss of pain free periods
P Pattern change
Precipitation Valsalva, exertion
Orthostatic
Postural
Pregnancy and postpartum
Dodick Adv Stud Med. 2003
Adapted from Dodick DW. Semin Neurol 2010
Migraine Is..
Real
• Not “just a headache”: neurological, sensory, autonomic, vestibular,
cognitive, and gastrointestinal symptoms
• Chronic neurologic disease involving disordered sensory processing,
influenced by genetics and the environment
Common
• > 47 million Americans
• 10% of school-age children
• 7% have chronic migraine (>15 headache days/month)
Disabling
• Leading cause of years lived with disability in people under the age of 50
worldwide
• Peak prevalence during working years 25-55 years of age
Burch et al Headache 2021

GBD 2016, Lancet 2017
Migraine Is Often Misdiagnosed
Inaccurate
diagnoses
received by
migraine
patients
>
-
3hus
deberigdeeneration
% Misdiagnosis
Lipton RB, et al. Headache. 2001;41:638-645.

The prevalence and impact of migraine and severe headache in
the United States: Updated age, sex, and socioeconomic-specific
estimates from government health surveys
Insurance Status Employment Status

18% are uninsured 38% are unemployed
SOCIAL
DETERMINANTS
Social Contributors to
OF HEALTH Headache Disparities
IMPACTING
MIGRAINE Education Level Income Level
34% have high school 42% are poor or near poor
diploma or below
Redrawn from: Burch et al Headache 2021

Headache: The Journal of Head and Face Pain, Volume: 61, Issue: 1, Pages: 60-68, First published: 21 December 2020, DOI: (10.1111/head.14024)
©2022 Mayo Foundation for Medical Education and Research | WF1137758-9

So how do we ICHD-3: 1.1 Migraine ID-Migraine
A. At least 5 attacks
make the B. Headache lasts 4-72 hours • P – photophobia
diagnosis of C. 2 of the following 4:
A. Unilateral location
• Does light bother you when you
have a headache?
migraine? B. Pulsating quality • I – impairment

• Do you feel impaired or avoid
C. Moderate or severe activities when you have a
intensity headache?
D. Aggravation by or causing
avoidance of routine • N – nausea
physical activity • Do you have nausea when you
have a headache?
D. At least 1 of the following:
A. Nausea and/or vomiting
B. Photophobia and
phonophobia
E. Not better accounted for by 2/3 symptoms = 93% PPV
another ICHD-3 diagnosis
3/3 symptoms = 98% PPV
Cephalalgia 2018.
Lipton RB et al. Neurology 2003.
The Trouble
with Numbers
Patient Says Doctor Hears Patient means
4 migraines 4 days of migraine 4 episodes of 3 day each
attack
It’s all Cluster migraines ?? Please stop

Googling.
Several migraine attacks or days
in a row
about Migraine Migraine Migraine with aura, not ”the

other headaches” (migraine
without aura)
the
words! Semantics matter.
Asthma : Asthma Attack :: Migraine : Migraine Attack
Language reflects the experience of a chronic neurologic disease
Parikh SK, Young WB. 2019 Feb 9;23(1):8.

• How many migraine attacks do you have in a
month? 4
• How long does the episode last for? 2 days
Ask-Tell-Ask • Any other types of headache? No
Dialogue • How many days per week/month are you
completely headache free ~5 d/week
• 4 migraine attacks per month, each lasting 2
days = 8 headache days per month
Deven has episodic migraine

Make the diagnosis
Anthony M. Clin Neurol Neurosurg 94(4):297-301, 1992 my.clevelandclinic.org/health/diseases/5005-migraine-headaches

We’ve diagnosed Deven with He has never been given How do we help him?
migraine! prescription medication in the past
Part 2: Optimizing Acute Migraine Treatment

Now What?
What else do we want to know What do we prescribe?

about his attacks?
Guidelines Level A Level B
All triptans Anti-emetics: IV
Guidelines
Acute DHE NS Metoclopramide &
Prochlorperazine
migraine
Acute NSAIDs: Diclofenac, aspirin,
naproxen, ibuprofen
Anti-dopamine: IV
treatment
Migraine Acetaminophen/aspirin/caffeine
Chlorpromazine &
Droperidol IV
Ergots: IM/IV DHE
Treatment non-incapacitating attacks) NSAIDS: Ketorolac
DHE, dihydroergotamine; NS, nasal spray; NSAID, non-steroidal

anti-inflammatory drug; IV, intravenous; IM, intramuscular
Marmura MJ. Headache 2015

Next Generation Oral
Acute Treatments
FDA approved for acute treatment
• Gepants
• Ubrogepant 50mg or 100mg during attack, repeat once as needed
• Rimegepant 75mg orally disintegrating tablet (ODT) once during
attack
• Zavegepant 10mg nasal spray, once during attack
• Ditans
• Lasmiditan 50mg, 100mg, 200mg once during attack
Consider in those who have (any of below)

• Found 2 triptans ineffective/had side effects
• Contraindications to standard therapy
Dodick DW. NEJM 2019; Lipton RB. JAMA 2019; Lipton RB. NEJM 2019;
Croop R. Lancet. 2019; Kuca B. Neurology 2018; Goadsby PJ. Brain 2019;
Digre K Headache 2018; Ailani J Headache 2021
Troubleshooting triptans – first-line for acute
treatment!
Increasing
Headache Inconsistent
Partial response: No response: need/needing to use
recurrence: response:
more often:
• Take a second dose • Take a second dose • After 2 adequate • Incresae the dose • Establish use limits
• Treat early • Increase the dose trials, try another • Take early • Add prevention
• Combine with given medication (or a • Switch to non-oral
NSAID different triptan) formulation
• Add prevention
Decision Making
How to
• Speed of onset of attack (fast onset
select the may benefit from non-oral route)
right option • Severity of attack (migraine specific)
• Associated gastrointestinal symptoms
for your (non-oral route of administration)
patient
How to • Response to generic options

(ineffective/side effects)
choose new • Contraindications
treatments (Cardiovascular/Safety concerns/Age)
Ubrogepant works in pre-headache prodrome/aura before pain
my.clevelandclinic.org/health/diseases/5005-migraine-headaches
Gepants Can be Used Early with Excellent Tolerability
Pre-Headache Treatment with Ubrogepant1
Absence of Moderate to Severe Headache Pain • Evaluated a set of migraine patients who could reliably
Within 24 Hours After Dosing predict the onset of migraine pain within 1-6h
100
• PRIMARY ENDPOINT
• Absence of headache pain of moderate to severe
80
2.1x more likely to avoid headache pain* †
intensity within 24 hours after taking ubrogepant100 mg
during the pre-headache phase (1-6 hours prior to
% of Patients
60
46%* onset of headache
40 • N-477
29%
20
(121/423) (190/418)
0
Placebo Ubrogepant
UBRELVY 100 mg
Odds ratio 2.09 (95% CI, 1.63-2.69)
*P<0.0001 vs placebo. †Odds ratio (95% CI) is based on a generalized mixed model with treatment group and treatment period as categorical fixed
effects.
CI=confidence interval.
1. Dodick DW et al Lancet 2023; 402: 2307–16.
Evaluation of Migraine Acute Treatment Efficacy
Migraine ACT: A score of <2 suggests need for a switch
Dowson AJ et al. Cur Med Res Opin. 2004;20:1125-1135.

Tepper SJ et al. Headache Care. 2005;2:27-31
Migraine Treatment Optimization Questionnaire (MTOQ-6)

Serrano et al. Headache 2015;55:502-518.
Part 3: Frequent Attacks of Migraine
• Over the last 2 years, Deven has seen a gradual worsening of

migraine and is now having 34 attacks per month
• His triptan is not consistently effective and ends up missing
work about once per month
• He has been using ibuprofen most days to ward off attacks as
well
Ask about attack duration and frequency
• Ask about # of migraine days/week (or
month)
• Ask about # of headache days/week
(or month)
• Ask how many days per week/month
they are completely headache free
• Ask about any days that are
unaccounted for – the numbers
should all add up!
• Devin has 3-4 migraine attacks per
month, but about 25 headache days
per month and 6 completely
headache free days/month = he has
chronic migraine!
Beyond attack duration and frequency
• What if Devin’s headache
calendar looked like this?
• What additional questions
should we ask him to determine
if he would benefit from
preventive treatment?
• HIT-6/MIDAS/MSQ-R
Important to also consider attack-related disability..
Prevention HEADACHE DEGREE OF

should be… DAYS/MONTH DISABILITY*
None
Offered Some
Severe
4 or 5 None
Considered 3 Some
2 Moderate
Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society. The American Headache
Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache. 2021
Jul;61(7):1021-1039. doi: 10.1111/head.14153. Epub 2021 Jun 23. PMID: 34160823.
Disability by frequency
Lipton et al. Overcome. Headache 2022

Migraine-Associated Disability
• Interictal burden is the 30
26.0
impairment between migraine 25
attacks
Respondents (%)
20
• Anxiety about the next attack
14.8
• Avoidance: fear of making plans 15
10.6
• Persistence of symptoms 10
• Total migraine burden = ictal + 5

interictal burden
0
• Both are targets of preventive Interictal anxiety Interictal Not free of all
treatment avoidance symptoms
Lampl C et al. J Headache Pain. 2016;17:9.

Bryson J et al. Neurology. 2010;16:254–261 .
Language Updates
• No longer recommend using the term “migraines”
• Proper terminology is “migraine,” “migraine attacks,” or
“chronic migraine”
• Reasoning: migraine is a singular neurological disorder with
multiple attacks, and has disability associated both within
attacks and outside of attacks (ictal + interictal burden)
Robbins et al Headache 2020

Robbins et al Neurology 2020
AHS CONSENSUS STATEMENT: UPDATE ON
INTEGRATING NEW MIGRAINE TREATMENTS INTO
CLINICAL PRACTICE*
Established Efficacyb Probably Effectivec
Oral Parenteral Oral Parenteral
Candesartan Eptinezumab Amitriptyline OnabotulinumtoxinA + CGRP mAbe,f
Divalproex sodium Erenumab Atenolol
Frovatriptand Fremanezumab Lisinopril
Metoprolol Galcanezumab Memantine
Propranolol OnabotulinumtoxinAe Nadolol
Timolol Venlafaxine
Topiramate Atogepant
Rimegepant
Valproate sodium
CGRP, calcitonin gene-related peptide; mAb, monoclonal antibody
*The decision to prescribe preventive therapy in women who are pregnant or of childbearing age should be based on the needs of individual
patients and available safety data.
bTwo or more Class I trials based on American Academy of Neurology evidence classification
cOne Class I or 2 Class II trials based on American Academy of Neurology evidence classification
dShort-term prevention of menstrual-related migraine; evaluated and rejected by the FDA for this indication
ePrevention of chronic migraine
fOne Class IV trial based on American Academy of Neurology evidence classification
Ailani et al. Headache 2021
©2021 Mayo Foundation for Medical Education and Research | slide-31

Disease-specific preventive treatments: CGRP
mAbs
Erenumab Galcanezuamb Fremanezuamb Eptinezuamb
CGRP target Receptor Peptide Peptide Peptide
Ab type Fully human Humanized Fully humanized Humanized
Indication EM, CM
EM, CM EM, CM EM, CM
approved eCH
Formulation SQ SQ SQ IV
Frequency Monthly Monthly Monthly, Quarterly Quarterly
240mg loading 225mg (monthly) or 100mg, 300mg
dose, 120mg 675mg (quarterly)
Dosing 70mg, 140mg maintenance dose
(300mg monthly
dose for eCH)
EM, episodic migraine; CM, chronic migraine; eCH, episodic cluster headache
Dodick DW. Cephalalgia. 2019
In women, all CGRP mAbs should be discontinued at least 5 months prior to attempting pregnancy. Ailani J et al Headache 2021
INDIVIDUALIZING THE CHOICE OF TREATMENT WITH GEPANTS
Ubrogepant 50mg, 100mg (acute) Zavegepant 10mg NS (acute) Rimegepant 75mg orally
•For patients who might want the option of a •For patients who prefer a non-oral option, have disintegrating tablet (acute and
second dose within 24 hours early nausea/vomiting, fast time to peak pain preventive)
•Shown to be effective when taken during •For patients who want the convenience of an
prodrome phase oral dissolving tablet for acute treatment
spranasal •For patients with episodic migraine who want

to try CGRP preventive therapy, but want to try
something with a shorter half-life than mAbs
Atogepant 10mg, 30mg, 60mg

(preventive)
•For patients with episodic migraine who want
to try CGRP preventive therapy, but want to try
something with a shorter half-life than mAbs
VanderPluym J, Halker Singh R, et al. JAMA 2021

Ailani J et al. Headache 2021
Urtecho M et al Headache 2023
Ailani J et al JAMA 2021
Croop R et al Headache 2022

MOH: UPDATES IN UNDERSTANDING
FROM THE MOTS TRIAL
• Methods: 720 participants with migraine & MOH
randomized to 1) preventive treatment only or 2)
preventive treatment & switching to alternative
acute treatment (max 2 days/week)
• Primary outcome: Migraine preventive
medication without switching of the overused
medication was not inferior to preventive
medication with switching for moderate-to-
severe headache day frequency during weeks 9-
12
• Secondary outcome: Switching group had
reduced their consumption of medication by 52%
(vs 32% in the non-switching group) at weeks 9-
12
• Conclusion: For patients with CM and
medication overuse, the efficacy of starting or
optimizing preventive medication is not MOH, medication-overuse headaches; MOTS, Medication Overuse
dependent on whether patients first reduce their Treatment Strategy; CM, chronic migraine; SD, standard deviation
use of acute medication
Schwedt et al. Neurology 2022;98:e1409-e1421
16319 Records identified through database 185 Additional records identified
and clinical trial registries through other sources
16504 Title and abstract screened
14456 Title and abstract excluded
2048 Full-text articles assessed for eligibility
1597 Full-text articles excluded

540 Intervention not of interest
413 Type of publication not of interest
186 Outcome not of interest
167 Not published in English
121 Not appropriate study design
• Use of triptans, NSAIDs, 83 Duplicate study

78 Population not of interest
9 Comparator not of interest
acetaminophen, DHE, CGRP 315 Systematic reviews and clinical trials

from clinical trial registries used to
antagonists, lasmiditan, & some non- identify additional studiesb
160 Completed relevant trials identified
drug treatments were associated with from clinical trial registries

90 Relevant systematic review/
meta-analysis (other than triptans
improved pain and function and NSAIDs)

36 Relevant ongoing clinical trials
from clinical trial registries
29 Relevant trials from clinical trial
• The evidence for opioids in the acute registries with unclear status
treatment of migraine is limited 115 Randomized clinical trials other than 15 Systematic reviews included for
Triptans and NSAIDs (121 articles) triptans and NSAIDs
Redrawn from: JAMA. 2021;325(23):2357-2369. doi:10.1001/jama.2021.7939

e ee
a
de estudiando
de
tobado
Discuss pearls to recognizing Ask about headache free days!
migraine & chronic migraine
Discuss key considerations to new Consider a gepant in patients who

have tried at least 2 triptans
migraine therapies & how to Consider a non-oral option in
choose between options patients with early nausea/vomiting
Summary
Ask about attack frequency, acute
Identify candidates for migraine medication use
prevention Consider attack-related disability
Discuss updates in the

management of acute medication Starting preventive therapy is most
overuse / medication overuse important!
headache
EVALUATION AND
MANAGEMENT OF
INITIAL AND
RECURRENT TIA
IN THE PRIMARY CARE SETTING
Courtney Hrdlicka, MD
Clinical Reviews 2024: 35th Annual Family Medicine and
Internal Medicine Update
February 21-24, 2024
©2021
©2021
MayoMayo
Foundation
Foundation
for Medical
for Medical
Education
Education
and Research
and Research
| WF57138-1
| slide-1
DISCLOSURE OF RELEVANT FINANCIAL

RELATIONSHIP(S) WITH INELIGIBLE COMPANIES
• Nothing to disclose
REFERENCES TO OFF-LABEL USAGE(S)

OF PHARMACEUTICALS OR INSTRUMENTS
• Nothing to disclose
2
• 1. Identify the appropriate work‐up when a patient presents to
primary care complaining of transient ischemic attack (TIA)
LEARNING symptoms
OBJECTIVES • 2. Determine the appropriate medical management strategies for
patients with recurrent TIAs
WHAT IS A TRANSIENT ISCHEMIC ATTACK?

IT’S COMPLICATED…
• Transient ischemic attack vs stroke – What’s the difference?

• 24 hours of symptoms?
• Infarction on MRI?
• Does it matter?
4
• Three common categories of transient neurologic symptoms:

• Stroke (or any kind of cerebrovascular ischemia, transient ischemic attacks included)
• Seizure
• Migraine (or other kinds of cortical spreading depression)
• Migraine aura
• Late life migraine accompaniment
• Amyloid spells, aka transient focal neurologic episodes (TFNEs)

• How to differentiate?
6
• How to differentiate:


• Abrupt onset, but can wax and wane
• Seizure
• Spread over seconds
• Migraine aura
• Spread over minutes
8

• Abrupt onset, but can wax and wane
• Negative symptoms
• Seizure
• Spread over seconds
• Positive or negative symptoms
• Migraine aura
• Spread over minutes
• Positive or negative symptoms

• Uncertainty and misdiagnosis are common!
10
TRANSIENT ISCHEMIC ATTACK WORKUP
11
TRANSIENT ISCHEMIC ATTACK WORKUP
• Magnetic resonance imaging (MRI) or computerized tomography (CT) head without contrast.
• Vessel imaging
• Transthoracic echocardiogram (TTE)
• Electrocardiogram (ECG)
• Labs:
• Complete blood count (CBC), Complete metabolic panel (CMP)
• Lipid panel
• Hemoglobin A1c
• Thyroid stimulating hormone (TSH)
• Why? Hypothyroidism contributing to hypertension, hyperlipidemia, and coagulation
disorders. Hyperthyroidism as a risk factor for atrial fibrillation
• Extended cardiac telemetry
• 30 day duration to evaluate for atrial fibrillation
• Ensure it is extended telemetry, not a symptom triggered/event monitor.
12
TRANSIENT ISCHEMIC ATTACK MANAGEMENT
ANTITHROMBOTICS
13

ANTITHROMBOTICS
•Anticoagulation • Antiplatelet
14
ANTITHROMBOTICS
• Assuming there is no known indication for anticoagulation (e.g. atrial fibrillation; deep vein
thrombosis or pulmonary embolism; mechanical valve…), antiplatelet therapy is indicated.
• You generally do NOT need both anticoagulation and antiplatelet therapy (large artery
atherosclerosis + an indication for anticoagulation is sometimes an exception)
15
Short-Term Dual Antiplatelet Therapy (DAPT)

After High-Risk Transient Ischemic Attack or Minor Stroke
• Three major randomized controlled trials1, 2, 3 have shown benefit of temporary dual antiplatelet
therapy after high-risk transient ischemic attack or minor stroke.
1. Wang Y, Wang Y, Zhao X, et al. Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack. N Engl J Med 2013;369:11-19
2. Johnston SC, Easton JD, Ferrant M, et al. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N Engl J Med 2018:379:215-25
3. Johnston SC, Amarenco P, Denison H, et al. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. N Engl J Med 2020;393:207-17©2020 MFMER | 3969547-16
16
Short-Term Dual Antiplatelet
Therapy
After High-Risk Transient Ischemic Attack or
Minor Stroke
Background: Therefore:
• Daily recurrent stroke risk is highest in the first • Benefit of DAPT outweighs risk early
days/weeks after a TIA or stroke and decreases after TIA or stroke, but there is an
relatively quickly inflection point at which risk starts to
outweigh benefit.
• Daily bleeding risk an any antithrombotic therapy is
• Hence, short- but not long-term
stable over time after a TIA or stroke.
DAPT has benefit1
• Cumulative bleeding risk increases linearly
1. Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the Prevention of Stroke in Patients
With Stroke and Transient Ischemic Attack: A Guideline from the American Heart Association/American
Stroke Association. Stroke 2021;52:e364-e467. DOI:10.1161/STR.0000000000000375 ©2020 MFMER | 3969547-17
17
Short-Term Dual Antiplatelet Therapy

• Why not in moderate or severe strokes?

e
i
noof
P ries
el
go
Transformaciogi
de
©2020 MFMER | 3969547-18
18
Short-Term Dual
Antiplatelet Therapy
After High-Risk Transient Ischemic Attack
or Minor Stroke
• Why not in moderate or severe strokes?

• Higher risk of hemorrhagic transformation
©2020 MFMER | 3969547-19
19
Short-Term Dual Antiplatelet Therapy *Control for all three trials was placebo plus aspirin
^Aspirin 162 x 5 days followed by 81 daily
After High-Risk Transient Ischemic Attack or Minor Stroke recommended
CHANCE1 POINT2 THALES3

Intervention Timing Study drug started <24 hrs Randomized <12 hrs from Randomized <24 hrs from
from symptom discovery stroke onset symptom discovery (wake-ups
<24h from last known well time)
Intervention* aspirin 75 daily (+/- load) + aspirin 50-325 daily^
(+/- load) aspirin 75-100mg (300-
clopidogrel 75 daily (300 + clopidogrel 75 daily (600 325mg load) + ticagrelor
load) -> clopidogrel load) -> ASA monotherapy 90mg bid (180mg load)
monotherapy to finish 90d
Duration of dual 21 days 90 days 30 days
antiplatelet therapy
Primary Outcome New stroke (ischemic or Composite of ischemic stroke, Composite of stroke
hemorrhagic) at 90 days myocardial infarction or (ischemic or hemorrhagic) or
ischemic vascular death at 90 all-cause mortality at day 30
days
3. Johnston SC, Amarenco P, Denison H, et al. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. N Engl J Med 2020;393:207-17 ©2020 MFMER | 3969547-20
20
Short-Term Dual Antiplatelet Therapy
CHANCE1 POINT2 THALES3
Primary Outcome Aspirin DAPT ARR Aspirin DAPT ARR Aspirin DAPT ARR
Result 11.7% 8.2% 3.5% 6.5% 5% 1.5% 6.6% 5.5% 1.1%
p<0.001 p=0.02 p=0.02
Major Aspirin DAPT ARI Aspirin DAPT ARI Aspirin DAPT ARI
Hemorrhage 0.2% 0.2% 0 0.4% 0.9% 0.5% 0.1% 0.5% 0.4%
Rates
p=0.94 p=0.02 p=0.001
Trial discontinued early due to

excess hemorrhage in DAPT
group
3. Johnston SC, Amarenco P, Denison H, et al. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. N Engl J Med 2020;393:207-17 ©2020 MFMER | 3969547-21
21
When to stop Dual

Antiplatelet Therapy ?
or Minor Stroke
• A meta-analysis1 of CHANCE2, POINT3 and
a prior small trial from 20074 showed:
• The vast majority of stroke risk reduction
occurs in the first 10 days (absolute risk
reduction 2%, odds ratio 0.64 [95%
confidence interval 0.55-0.76])
• Essentially no benefit days 22-90 (odds
ratio 1.47 [95% confidence interval 0.84-
2.56])
1. Hao Q, Tampi M, O’Donnell M, et al. Clopidogrel plus aspirin versus aspirin alone for acute
minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-
analysis. BMJ 2018;363:k5108
2. Wang Y, Wang Y, Zhao X, et al. Clopidogrel with Aspirin in Acute Minor Stroke or Transient
Ischemic Attack. N Engl J Med 2013;369:11-19
3. Johnston SC, Easton JD, Ferrant M, et al. Clopidogrel and Aspirin in Acute Ischemic Stroke
and High-Risk TIA. N Engl J Med 2018:379:215-25
4. Kennedy J, Hill MD, Ryckborst KJ, et al. Fast assessment of stroke and transient ischaemic
attack to prevent early recurrence (FASTER): a randomized controlled pilot trial. Lancet Neurol Figure from: Hao Q, Tampi M, O’Donnell M, et al. Clopidogrel plus aspirin versus aspirin
alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic
2007;6:961-9 review and meta-analysis. BMJ 2018;363:k5108 ©2020 MFMER | 3969547-22
22
When to stop Dual
Antiplatelet Therapy ?
or Minor Stroke
• A meta-analysis1 of CHANCE2, POINT3 and
a prior small trial from 20074 showed:
• The vast majority of stroke risk reduction
occurs in the first 10 days (absolute risk
reduction 2%, odds ratio 0.64 [95%
confidence interval 0.55-0.76])
• Essentially no benefit days 22-90 (odds
ratio 1.47 [95% confidence interval 0.84-
2.56])
• Following this, 21-day duration of DAPT was
widely adopted by stroke neurologists.
1. Hao Q, Tampi M, O’Donnell M, et al. Clopidogrel plus aspirin versus aspirin alone for acute
minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-
analysis. BMJ 2018;363:k5108
2. Wang Y, Wang Y, Zhao X, et al. Clopidogrel with Aspirin in Acute Minor Stroke or Transient
Ischemic Attack. N Engl J Med 2013;369:11-19
3. Johnston SC, Easton JD, Ferrant M, et al. Clopidogrel and Aspirin in Acute Ischemic Stroke
and High-Risk TIA. N Engl J Med 2018:379:215-25
4. Kennedy J, Hill MD, Ryckborst KJ, et al. Fast assessment of stroke and transient ischaemic
attack to prevent early recurrence (FASTER): a randomized controlled pilot trial. Lancet Neurol Figure from: Hao Q, Tampi M, O’Donnell M, et al. Clopidogrel plus aspirin versus aspirin
alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic
2007;6:961-9 review and meta-analysis. BMJ 2018;363:k5108 ©2020 MFMER | 3969547-23
23

LIPID LOWERING THERAPY
24
Lipid Lowering
For Secondary Stroke Prevention
• Practice-changing study published in 2020: Treat Stroke to Target1
• 2860 patients from France and Korea within 3 months of atherosclerotic stroke -or- any stroke +
history of coronary artery disease
• Randomized to low density lipoprotein (LDL) targets 50-70 vs 90-110

• Providers able to use any lipid-lowering therapy to achieve/maintain these goals.
• Primary outcome: Composite of major cardiovascular events (MCVE)
1. Amarenco P, Kim JS, Labreuche J, et al. A comparison of two LDL cholesterol targets after ischemic stroke. NEJM. 2020;382:9-19
©2020 MFMER | 3969547-25
25
Lipid Lowering – Treat Stroke to Target definitiva

For Secondary Stroke Prevention
After median follow-up 3.5 years1:

importa
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o-70
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End Point Lower Higher Absolute Risk Hazard Ratio (95%

Target Target Difference Confidence Interval)
Major Cardiovascular 8.5% 10.9% -2.4% 0.78 (0.61-0.98), p=0.04
Events
Ischemic Stroke 5.7% 7.0% -1.3%
Nonfatal Acute 1.0% 1.6% -0.6%
Coronary Syndrome
Intracranial 1.3% 0.9% +0.4%
Hemorrhage
Amarenco P, Kim JS, Labreuche J, et al. A comparison of two LDL cholesterol targets after ischemic stroke. NEJM. 2020;382:9-19
©2020 MFMER | 3969547-26
26
RECURRENT TRANSIENT ISCHEMIC ATTACK
WORKUP
Same symptoms as previous event: Different symptoms than previous event:
27

WORKUP

• Think harder about vascular lesions
• Stuttering lacunar infarcts – short time
interval, need admission.
• Reconsider your diagnosis
• Seizure?
• Cortical spreading depression?
• Consider Neurology referral if available
28
WORKUP

• Think harder about vascular lesions • Repeat the full workup
• Vessels
• Stuttering lacunar infarcts – short time
interval, need admission. • Echocardiogram
• Labs can be deferred if previously
• Reconsider your diagnosis checked within the last few months.
• Seizure?
• Cortical spreading depression?
29

TREATMENT
• Aspirin “failure”
30
WHAT TO DO: ASPIRIN “FAILURE”
• 2021 American Heart Association Get with

the Guidelines Stroke Registry study
• 100,016 stroke patients from 1734
hospitals 2012-2017 who had been
taking aspirin at the time of the stroke
Lusk JB, Xu H, Peterson ED, et al. Antithrombotic Therapy for Stroke

Prevention in Patients With Ischemic Stroke With Aspirin Treatment Failure.
Stroke. 2021 Dec;52(12):e777-e781. doi:
10.1161/STROKEAHA.121.034622. Epub 2021 Oct 27. PMID: 34702067;
PMCID: PMC8608737.
31

WHAT TO DO: ASPIRIN “FAILURE”
• 2021 American Heart Association Get with

the Guidelines Stroke Registry study1
• 100,016 stroke patients from 1734
hospitals 2012-2017 who had been
taking aspirin at the time of the stroke
• Don’t anticoagulate for recurrent stroke

unless you have a definite indication*
1. Lusk JB, Xu H, Peterson ED, et al. Antithrombotic Therapy for Stroke

Prevention in Patients With Ischemic Stroke With Aspirin Treatment
Failure. Stroke. 2021 Dec;52(12):e777-e781. doi:
10.1161/STROKEAHA.121.034622. Epub 2021 Oct 27. PMID:
34702067; PMCID: PMC8608737.
32
TREATMENT
• Aspirin “failure”
• DOAC “failure”
33

WHAT TO DO: DIRECT ORAL ANTICOAGULANT “FAILURE”
• 2023 Canadian administrative database

study1
• 985 patients with atrial fibrillation-related
stroke despite a direct oral anticoagulant
(DOAC).
• Followed for median 1.75 years
1. Duong E, Lin M, Hodgson M, et al. Choice of Oral Anticoagulant:

Outcomes in Atrial Fibrillation Patients Post-Stroke Despite Direct Oral
Anticoagulant Use. CJC Open. 2023 May 8;5(8):603-610. doi:
10.1016/j.cjco.2023.05.001. PMID: 37720181; PMCID: PMC10502439.
34

study1 • Result:
• 985 patients with atrial fibrillation-related • 63% stayed on the same DOAC
stroke despite a direct oral anticoagulant • 8% same DOAC, different dose
(DOAC).
• 16% switched to a different DOAC
• 5% switched to warfarin
• 7% didn’t fill an anticoagulant
prescription

35


study1 • Result:
• 985 patients with atrial fibrillation-related • 63% stayed on the same DOAC
stroke despite a direct oral anticoagulant • 8% same DOAC, different dose
(DOAC).
• 16% switched to a different DOAC
• 5% switched to warfarin
• 7% didn’t fill an anticoagulant
prescription
• Rates of recurrent stroke or transient
ischemic attack recurrence did not differ
between the prescribing patterns.

36
WHAT DO I DO?
Shared decision making, but I err toward continuing the same antithrombotic.
37
WHEN SHOULD YOU REFER YOUR PATIENT TO

THE EMERGENCY DEPARTMENT?
38
• Persistent deficit that started within the past few days
• Recent (i.e. a few days) transient ischemic attack when you can’t arrange the workup (imaging,
echocardiogram, labs) to be done in the next few days as an outpatient.
• Very recent (i.e. a day or two) transient ischemic attack with high ABCD2 score
39
Short-Term DAPT - ABCD2 Score1,2

After High-Risk TIA or Minor Stroke
0 points 1 point 2 points

Age <60 ≥ 60
Initial BP <140/90 ≥ 140/90
Clinical Other symptoms Speech disturbance Unilateral weakness
Duration <10 min 10-59 min ≥ 60 min
History of Diabetes No Yes
• 0-3 points: Low risk with 2-day stroke risk 1.0%2

• 4-5 points: Moderate risk with 2-day stroke risk 4.1%2
• 6-7 points: High risk with 2-day stroke risk 8.1%2
1. Rothwell PM, Giles MF, Flossman E, et al. A simple score (ABCD) to identify individuals at high early risk of stroke after
transient ischaemic attack. Lancet 2005;366:29-36
2. Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after
transient ischemic attack. Lancet 2007;369:283-92 ©2020 MFMER | 3969547-40
40
41

• Recent (maybe up to about a week or so?) transient ischemic attack localizing to the vascular
territory of a carotid artery with >50% stenosis
• Surgical evaluation still needed but may be appropriate as an outpatient if patient is
presenting later.
• Recurrent transient ischemic attack a short interval (i.e. a few weeks) after the first transient
ischemic attack.
• Recurrence of the same symptoms or different symptoms should both be admitted.
42
RESOURCES FOR WORKUP AND MANAGEMENT
OF TRANSIENT ISCHEMIC ATTACKS
GUIDELINES
43
RESOURCES FOR WORKUP AND MANAGEMENT

OF TRANSIENT ISCHEMIC ATTACKS
GUIDELINES
• 2021 American Heart Association “Guideline for the Prevention of Stroke in Patients with
Stroke and Transient Ischemic Attack”1
• 2022 American Academy of Neurology “Stroke Prevention in Symptomatic Large Artery
Intracranial Atherosclerosis Practice Advisory”2
• 2023 Scientific Statement from the American Heart Association titled: “Aggressive LDL-C
Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke”3
1. Kleindorfer DO, Towfighi A, Chaturvedi S,et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the
American Heart Association/American Stroke Association. Stroke. 2021 Jul;52(7):e364-e467. doi: 10.1161/STR.0000000000000375. Epub 2021 May 24. Erratum in:
Stroke. 2021 Jul;52(7):e483-e484. PMID: 34024117.
2. Turan TN, Zaidat OO, Gronseth GS, et al. Stroke Prevention in Symptomatic Large Artery Intracranial Atherosclerosis Practice Advisory: Report of the AAN Guideline
Subcommittee. Neurology. 2022 Mar 22;98(12):486-498. doi: 10.1212/WNL.0000000000200030. PMID: 35314513; PMCID: PMC8967328.
3. Goldstein LB, Toth PP, Dearborn-Tomazos JL, et al; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular
and Stroke Nursing; Council on Peripheral Vascular Disease; and Stroke Council. Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and
Hemorrhagic Stroke: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol. 2023 Oct;43(10):e404-e442. doi:
10.1161/ATV.0000000000000164. Epub 2023 Sep 14. PMID: 37706297.
44
RESOURCES FOR
WORKUP AND
MANAGEMENT OF
TRANSIENT ISCHEMIC
ATTACKS
AMERICAN HEART ASSOCIATION
GUIDELINES
What workup to do?
1. Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J,et al. 2021
Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic
Attack: A Guideline From the American Heart Association/American Stroke
Association. Stroke. 2021 Jul;52(7):e364-e467. doi:
10.1161/STR.0000000000000375. Epub 2021 May 24. Erratum in: Stroke. 2021
Jul;52(7):e483-e484. PMID: 34024117.
45
RESOURCES FOR
WORKUP AND
MANAGEMENT OF
TRANSIENT ISCHEMIC
ATTACKS
GUIDELINES
What to do about extracranial vertebral artery

stenosis, do they need to see Neurosurgery?
Jul;52(7):e483-e484. PMID: 34024117.
46
RESOURCES FOR
WORKUP AND
MANAGEMENT OF
TRANSIENT ISCHEMIC
ATTACKS
GUIDELINES
What to do about a patent foramen ovale?
Jul;52(7):e483-e484. PMID: 34024117.
47
QUESTIONS
& DISCUSSION
48
THANK YOU FOR JOINING US IN THIS COURSE
Rochester, Minnesota Phoenix, Arizona Jacksonville, Florida
49
71% of patients
consult their primary care practitioner for migraine.
That’s why it’s essential that you have access to accurate, timely information on migraine
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Learn more and explore

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DIAGNOSIS, PREVENTION,

Clinical Reviews 2024: 35th Annual Family Medicine and

Part 1: Deven’s Bad Headaches Are Migraine

N Neurologic symptoms, signs Papilledema, sensory,

Burch et al Headache 2021

Lipton RB, et al. Headache. 2001;41:638-645.

Insurance Status Employment Status

Redrawn from: Burch et al Headache 2021

©2022 Mayo Foundation for Medical Education and Research | WF1137758-9

migraine? B. Pulsating quality • I – impairment

It’s all Cluster migraines ?? Please stop

about Migraine Migraine Migraine with aura, not ”the

Parikh SK, Young WB. 2019 Feb 9;23(1):8.

Deven has episodic migraine

Anthony M. Clin Neurol Neurosurg 94(4):297-301, 1992 my.clevelandclinic.org/health/diseases/5005-migraine-headaches

Part 2: Optimizing Acute Migraine Treatment

What else do we want to know What do we prescribe?

DHE, dihydroergotamine; NS, nasal spray; NSAID, non-steroidal

Marmura MJ. Headache 2015

Consider in those who have (any of below)

How to • Response to generic options

Dowson AJ et al. Cur Med Res Opin. 2004;20:1125-1135.

Migraine Treatment Optimization Questionnaire (MTOQ-6)

• Over the last 2 years, Deven has seen a gradual worsening of

Prevention HEADACHE DEGREE OF

Lipton et al. Overcome. Headache 2022

• Total migraine burden = ictal + 5

Lampl C et al. J Headache Pain. 2016;17:9.

Robbins et al Headache 2020

©2021 Mayo Foundation for Medical Education and Research | slide-31

spranasal •For patients with episodic migraine who want

Atogepant 10mg, 30mg, 60mg

VanderPluym J, Halker Singh R, et al. JAMA 2021

©2021 Mayo Foundation for Medical Education and Research | slide-33

16504 Title and abstract screened

14456 Title and abstract excluded

2048 Full-text articles assessed for eligibility

1597 Full-text articles excluded

• Use of triptans, NSAIDs, 83 Duplicate study

acetaminophen, DHE, CGRP 315 Systematic reviews and clinical trials

drug treatments were associated with from clinical trial registries

improved pain and function and NSAIDs)

Redrawn from: JAMA. 2021;325(23):2357-2369. doi:10.1001/jama.2021.7939

©2022 Mayo Foundation for Medical Education and Research | WF1137758-35

Discuss key considerations to new Consider a gepant in patients who

Discuss updates in the

DISCLOSURE OF RELEVANT FINANCIAL

REFERENCES TO OFF-LABEL USAGE(S)

©2021 Mayo Foundation for Medical Education and Research | WF57138-2

©2021 Mayo Foundation for Medical Education and Research | WF57138-3

WHAT IS A TRANSIENT ISCHEMIC ATTACK?

• Transient ischemic attack vs stroke – What’s the difference?

©2021 Mayo Foundation for Medical Education and Research | WF57138-4

• Three common categories of transient neurologic symptoms:

©2021 Mayo Foundation for Medical Education and Research | WF57138-5

WHAT IS A TRANSIENT ISCHEMIC ATTACK?

©2021 Mayo Foundation for Medical Education and Research | WF57138-6

©2021 Mayo Foundation for Medical Education and Research | WF57138-7

WHAT IS A TRANSIENT ISCHEMIC ATTACK?

• Three common categories of transient neurologic symptoms:

©2021 Mayo Foundation for Medical Education and Research | WF57138-8

• Three common categories of transient neurologic symptoms:

©2021 Mayo Foundation for Medical Education and Research | WF57138-9

WHAT IS A TRANSIENT ISCHEMIC ATTACK?