ic6 - antithrombotics in AMI and AIS (focus on antiplatelets)

Question 1

classify the types of coronary vascular diseases

Answer 1

cerebrovascular disease: carotid artery disease, cerebrovascular accident, TIA

coronary heart disease/ ischemic heart disease: stable angina, acute coronary syndrome

peripheral artery disease

Question 2

differentiate between stable angina and acute coronary syndrome

Answer 2

stable angina experiences chest pain on exertion and lasts <20min

acute coronary syndrome experiences chest pain at rest and includes STEMI, NSTEACS, NSTEMI, unstable angina

for ACS, if there is ECG changes within 10mins of presentation, ST elevation -> STEMI vs if no ST elevation -> NSTEACS

for NSTEACS if there is cardiac enzyme changes -> NSTEMI vs if there is no cardiac enzyme canges -> unstable angina

Question 3

how to diagnose acute coronary syndrome (ACS)

Answer 3

look at: clinical setting sx and vital signs, ECG, troponin change within 1-3h

Question 4

what is an angioplasty

Answer 4

using a tiny balloon catheter (may also have a stent) inserted in a blocked blood vessel at radial artery site to help widen it and improve blood flow bc the inflated ballon can compress the plaque and reopen the vessel

Question 5

what are the approaches for stent insertion

Answer 5

radial approach and femoral approach

Question 6

where are the possible sites for stent insertion

Answer 6

right coronary artery (RCA), circumflex artery (LCx), left anterior descending artery (LAD), obtuse marginal branch (OM1,2), diagonal branch (D1,2)

Question 7

what are the parts of a stent

Answer 7

stent platform, polymer coating/ embedded drug

Question 8

what are the types of stents that can be used and examples

Answer 8

1. bare metal stents (BMS)
2. first gen drug eluting stent (DES) - paclitaxel (taxus) or sirolimus (cypher)
3. second gen DES - everolimus, zotarolimus
4. third gen - various technologies like polymer free and carrier free

Question 9

what is the advantage second gen DES have over first gen

Answer 9

second gen DES were thought to be less thrombogenic

Question 10

what drug is typically given for angioplasty and why

Answer 10

immunosuppressants for antiproliferative effects (prevent proliferation of cells which may cause narrowing again)

but will also affect healing bc non specific and injured tissue and place foreign object means body will react to fight and heal thus may form clots again

Question 11

compare the difference between in stent thrombosis and in stent restenosis

Answer 11

IST: thrombus formation, indication for DAPT

ISR: neointimal overproliferation resulting in thickening of arterial walls and decreased arterial lumen space, DES thought to be solution

Question 12

compare the difference between various imagings

Answer 12

CT: uses x ray, takes 5-15mins, contrast may be needed depending on type of tests

MRI: uses magnetic fields and radio freq waves, takes 45mins-2hrs, contrast may be needed depending on type of tests, sees smaller structures (compared to US which sees gross structure aka soft tissues only)

Question 13

what are the types of stroke and its respective pathogenesis

Answer 13

1. ischemic stroke which is due to a blocked artery (blood clot blocks blood flow in an artery within the brain)
2. hemorrhagic stroke which is due to a ruptured artery (blood vessel in brain burst and presses against other tissues which may stop blood flow to other areas)

Question 14

what are the etiologies of stroke and what criteria is used to classify them

Answer 14

using TOAST criteria

large artery atherosclerosis (LAA)
cardioembolic stroke (CE)
small vessel disease (SVD)/ penetrating artery disease (PAD)
stroke of other determined cause
stroke of undertermined cause

Question 15

what is the scoring system used to assess stroke (and list its components)

Answer 15

NIHSS and mNIHSS

NIHSS: list of 15 items

mNIHSS: list of 11 items (omits level of consciousness, facial weakness, limb ataxia and dysarthria) (condenses sensory test choices from three to two responses compared to original NIHSS) (validity and reliability nearly identical to original NIHSS)

Question 16

what is the significance of the scoring systems and what constitutes as a mini stroke

Answer 16

NIHSS and mNIHSS evaluates the effect of acute cerebral infarct on various functions and is tied to eligibility for rtPA

considered mini stroke if score is 0-5

Question 17

what is dysarthria

Answer 17

muscles you use for speech are weak or you have difficulty controlling them

Question 18

using what scoring system and above what score indicates high risk for TIA

Answer 18

using ABCD2 evaluates risk for TIA, score 4 and above indicates high risk for TIA

age: 60 and above [1] below 60 [0]

BP elevation when first assessed after TIA: systolic 140 and above OR diastolic 90 and above [1] systolic below 140 AND diastolic below 90 [0]

clinical features: unilateral weakness [2] isolated speech disturbance [1]

DM: present [1] absent [0]

duration of TIA sx: 60mins and longer [2] 10-59mins [1] below 10mins [0]

Question 19

what is the tx algorithm for stroke

Answer 19

step 1: new onset AIS and not on antithrombotic tx

step 2: determine if eligible for rtPA (eligible if NIHSS or mNIHSS score 0-5 but ineligible if present after 3-4.5h window or too severe)

step 3: [if eligible for rtPA] start on SAPT (aspirin) on 24h within 48h [if not eligible for rtPA] look at if there is minor stroke and assess risk for TIA

step 4: [if minor stroke or high risk TIA] start on DAPT for 21d [if no minor stroke and not high risk TIA] start SAPT asap

step 5: for all assess stroke mechanism using (i) MRI for brain (ii) 24h holter (iii) TTE (iv) US carotids (v) lipid panel, TFTs, HbA1c

step 6: based on stroke mechanism, determine whether it is cardioembolic or not

step 7: [if cardioembolic] stop SAPT as ineffective (and maybe switch to DOAC bc if underlying AF should start OAC) [if non cardioembolic] determine if major severe intracranial arterial stenosis (ICAS)

step 8: [if major severe ICAS] add clopidogrel to aspirin for 90d then life long SAPT [if not major severe ICAS] straight to life long SAPT

step 9: also consider adding atorvastatin 40-80mg OD or rosuvastatin 20-40mg if no absolute c/i

Question 20

describe the journey of an MI pt

Answer 20

on the way to hospital, load aspirin -> at AnE, give thrombolytics (once scan confirm AIS) -> at catheter lab, give UFH bolus and eptifibatide (GPIIb/IIIai) -> in ICU, give DAPT (and OAC as per indication but not to start within 24h of rtPA) -> in general ward, consider risk for VTE due to immobility and thus decide if give LMWH for VTEp within 48h (but after 24h if rtPA given) -> at home, SAPT lifelong while DAPT 21d or 90d

Question 21

what are the specific recommendations to note under stroke guidelines

Answer 21

to not give aspirin, heparin, warfarin and other anticoagulants or antiplatelets within 24h of giving IV rtPA to a pt for tx of AIS

but also DAPT (eg. clopidogrel and aspirin as per in tx algorithm) can be started since benefit noted for those with mechanical thrombectomy and catheter stents

Question 22

list examples of antiplatelets

Answer 22

aspirin, clopidogrel, ticagrelor, eptifibatide

Question 23

what class of drugs are clopidogrel and ticagrelor

Answer 23

P2Y12 inhibitors

Question 24

are P2Y12 inhibitors given as loading doses

Answer 24

PO P2Y12 inhibitors are usually loaded when initiating

Question 25

compare between the P2Y12i (drug class, moa, Tmax, time to peak PLT inhibition, time to PLT aggregation ss, metabolism and half life, elimination, ddi, food effect, ethnic considerations, when to stop for surgery, quirks)

Answer 25

clopidogrel: thienopyridine, irreversible inhibition, 1h, >6h for 300mg LD 2h for 600mg LD, 5-6d, prodrug 2 step activation by 3A4 1A2 2B6 (less from 2C19 and 2C9), 1.9h (50% urine), 2C19 3A P-gp, F unaffected by food, stop for at least 5d, affected by 2C19 and 2C9 polymorphisms

ticagrelor: cyclopentyltriazolopyrimidine, reversible inhibition, 1.5h for parent 2.5h for active metab, 2h, 2d, no biotransformation, 7h for parent 9h for active metab, 2C19 3A4 P-gp 2C9 1A2, unaffected by food, consider japanese, stop for at 2-3d, incr risk of bleeding vs clopidogrel, adenosine s/e (dyspnea and bradycardia), incr SCr, c/i for severe renal impairment

prasugrel: thienopyridine, irreversible inhibition, 30mins, 1-1.5h, 2-4d, 7.4h (70% urine), fasting preferred, consider japanese, incr risk of bleeding vs clopidogrel, caution if >75yo, avoid if hx of stroke/TIA

Question 26

compare between aspirin, clopidogrel, dipyridamole, ticagrelor and eptifibatide their route, dose, concerns and quirks

Answer 26

aspirin: PO, 300mg LD f/b 100mg OM (lifetime), can be used as monotx, concerned with bleeding, usually part of DAPT

clopidogrel: PO, 600mg LD or 300mg LD f/b 75mg OM, can be used as monotx, concerned with bleeding and hypersensitivity, 2C19 polymorphisms LoF results in increase risk of adverse CV and cerebrovascular events

dipyridamole: PO, 25-150mg TDS, concerned with flushing and dizziness and abdominal distress, may be considered as part of DAPT if high risk bleed

ticagrelor: PO 180mg LD f/b 90mg BD up to 12m f/b 60mg BD for extended tx, can be used as monotx, concerned with bleeding and dyspnea and bradycardia, not affected by 2C19 polymorphisms thus > clopidogrel (in most ACS but not CCS) but incr bleeding risk

eptifibatide: IV, double bolus of 180mcg/kg, concerned with short half life and thus need to be infused for 72h, CrCl <50 must dose adjust and is c/i for ESRD

Question 27

what are the things to note for follow up and monitoring for antiPLT given for AIS

Answer 27

1. duration of antiPLT: aspirin given lifelong, P2Y12i given as per indication
2. monitoring: bleeding and FBC (and dyspnea if given ticagrelor)
3. counselling: thrombogenicity of cardiac stents, adherence to DAPT, duration of DAPT, when to stop antiPLT for invasive procedures

Question 28

how to choose which P2Y12i for which group of pts

Answer 28

ACS -> ticagrelor 180mg LD 90mg BD with aspirin

ACS undergoing PCI -> prasugrel 60mg LD 10mg QD with aspirin

stable CAD undergoing stent implant or c/i for ticagrelor and prasugrel -> clopidogrel 600mg LD 75mg QD with aspirin

75yo and younger with NSTEMI recieving thrombolysis -> clopidogrel 300mg LD 75mg QD with aspirin

if coronary anatomy unknown, rec to give P2Y12i

Question 29

what is the tx algorithm for ACS with PCI

Answer 29

step 1: for PCI, give anticoagulant (UFH, LMWH aka enoxaparin, bivalirudin)

step 2: assess bleeding risk to decide antiPLT

step 3: all DAPT for 12m (AwP or AwT or AwC) unless bleeding risk high use AwC for 3m or bleeding risk very high then AwC for 1m

step 4: note A tx lifelong (eventually become monotx) EXCEPT for if bleeding risk very high, C monotx instead of A

Question 30

what is the tx algorithm for PCI for stable ischemic heart disease or CCS

Answer 30

DAPT tx is 6m then A lifelong monotx after

Question 31

how do you assess the bleeding risk after PCI and what is indicative of high risk bleeding

Answer 31

using PRECISE-DAPT scoring

if score >25 means high risk bleeding

if high risk bleeding, stop P2Y12i after 3m and continue A

Question 32

what are the major and minor criterias of PRECISE-DAPT scoring

Answer 32

determined at time of PCI

major: anticipated long term use of OAC, severe or end stage CKD (GFR <30), Hb <11, spontaneous bleeding req hospitalisation or transfusion in past 6m, moderate or severe baseline thrombocytopenia, chronic bleeding diathesis, liver cirrhosis with portal HTN, active malignancy, previous ICH, nondeferrable major surgery on DAPT, recent major surgery or major trauma within 30d before PCI

minor: above age 75, moderate CKD (30-59), Hb 11-12.9 for men 11-11.9 for women, spontaneous bleeding req hospitalisation or transfusion in past 12m, long term use NSAID or steroid

Question 33

what are the allele types for 2C19

Answer 33

*1 is wild type
*2 and *3 is LoF
*17 is GoF
1/17 or 17/17 is ultra rapid metabolisers
1/1 is extensive/ normal metabolisers
1/2 or 1/3 is intermediate metabolisers
2/2 or 2/3 or 3/3 is poor metabolisers

Question 34

what is the recommended antiPLT if there is *2 or *3 allele present

Answer 34

use ticagrelor

Question 35

what are CV risk factors

Answer 35

cholesterol

high BP (maintain <130/80)

adequate physical activity (at least 150mins/w of moderate or at least 75mins/w of vigorous physical activity)

aspirin use (low dose aspirin now reserved for selected high risk pts)

T2DM (control through diet and exercise, metformin as primary tx and SGLT2i or GLP1RA as secondary tx)

diet (intake of veges, fruits, nuts, legumes, fish and whole grains)

tobacco (pharmacotx and behavior interventions to maximise quit rates)