ic6 - antithrombotics in AMI and AIS (focus on antiplatelets) Flashcards
classify the types of coronary vascular diseases
cerebrovascular disease: carotid artery disease, cerebrovascular accident, TIA
coronary heart disease/ ischemic heart disease: stable angina, acute coronary syndrome
peripheral artery disease
differentiate between stable angina and acute coronary syndrome
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
how to diagnose acute coronary syndrome (ACS)
look at: clinical setting sx and vital signs, ECG, troponin change within 1-3h
what is an angioplasty
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
what are the approaches for stent insertion
radial approach and femoral approach
where are the possible sites for stent insertion
right coronary artery (RCA), circumflex artery (LCx), left anterior descending artery (LAD), obtuse marginal branch (OM1,2), diagonal branch (D1,2)
what are the parts of a stent
stent platform, polymer coating/ embedded drug
what are the types of stents that can be used and examples
- bare metal stents (BMS)
- first gen drug eluting stent (DES) - paclitaxel (taxus) or sirolimus (cypher)
- second gen DES - everolimus, zotarolimus
- third gen - various technologies like polymer free and carrier free
what is the advantage second gen DES have over first gen
second gen DES were thought to be less thrombogenic
what drug is typically given for angioplasty and why
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
compare the difference between in stent thrombosis and in stent restenosis
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
compare the difference between various imagings
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)
what are the types of stroke and its respective pathogenesis
- ischemic stroke which is due to a blocked artery (blood clot blocks blood flow in an artery within the brain)
- 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)
what are the etiologies of stroke and what criteria is used to classify them
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
what is the scoring system used to assess stroke (and list its components)
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)
what is the significance of the scoring systems and what constitutes as a mini stroke
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
what is dysarthria
muscles you use for speech are weak or you have difficulty controlling them
using what scoring system and above what score indicates high risk for TIA
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]
what is the tx algorithm for stroke
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
describe the journey of an MI pt
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
what are the specific recommendations to note under stroke guidelines
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
list examples of antiplatelets
aspirin, clopidogrel, ticagrelor, eptifibatide
what class of drugs are clopidogrel and ticagrelor
P2Y12 inhibitors
are P2Y12 inhibitors given as loading doses
PO P2Y12 inhibitors are usually loaded when initiating
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)
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
compare between aspirin, clopidogrel, dipyridamole, ticagrelor and eptifibatide their route, dose, concerns and quirks
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
what are the things to note for follow up and monitoring for antiPLT given for AIS
- duration of antiPLT: aspirin given lifelong, P2Y12i given as per indication
- monitoring: bleeding and FBC (and dyspnea if given ticagrelor)
- counselling: thrombogenicity of cardiac stents, adherence to DAPT, duration of DAPT, when to stop antiPLT for invasive procedures
how to choose which P2Y12i for which group of pts
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
what is the tx algorithm for ACS with PCI
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
what is the tx algorithm for PCI for stable ischemic heart disease or CCS
DAPT tx is 6m then A lifelong monotx after
how do you assess the bleeding risk after PCI and what is indicative of high risk bleeding
using PRECISE-DAPT scoring
if score >25 means high risk bleeding
if high risk bleeding, stop P2Y12i after 3m and continue A
what are the major and minor criterias of PRECISE-DAPT scoring
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
what are the allele types for 2C19
*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
what is the recommended antiPLT if there is *2 or *3 allele present
use ticagrelor
what are CV risk factors
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)
