Acute Coronary Syndrome (ACS)

what is the leading cause of death in the US?

cardiovascular disease (CVD)

what is acute coronary syndrome (ACS)?

a form of coronary heart disease (CHD)

- includes: unstable angina (UA), ST-elevation myocardial infarction (STEMI), & non-STEMI

- represent an imbalance between myocardial O2 supply/demand

what is chronic stable angina caused by?

stable plaques

- occluding >70% of a major coronary artery or >50% of the left main coronary artery

what is plaque rupture?

when the fibrous cap of a plaque bursts open

how does a clot form on top of the ruptured plaque?

- platelet aggregation/adhesion

- activation of clotting cascade

- fibrin & platelet clot forms

- physiological factors: collagen, ADP, TXA2, GP 2b/3a receptors, fibrinogen, fibrin, coagulation cascade, thrombin factor IIa, & others

- subsequently, a clot forms on top of the ruptured plaque

what is unstable angina (UA)?

ischemia is not severe enough to produce myocardial necrosis or release of biomarkers

- EKG: similar to non-STEMI

- clots: partially occlude coronary artery or may only transiently occlude the artery

what is a non-STEMI?

myocardial injury is limited to the subendocardial myocardium w/ less extensive damage as compared to STEMI

- EKG: possibly no changes, or ST depression or T wave inversions w/o Q waves

- clots: partially occlude the coronary artery

what is a STEMI?

myocardial necrosis transects the thickness of the myocardial wall

- tends to involve a higher level of coagulation cascade

- EKG: ST segment elevation >/= 1 mm in 2 contiguous leads or >/= 2mm in V2 or V3, or new LBBB

- total occlusion of coronary artery

what should you discuss w/ all pts who have a diagnosis of CHD?

- typical & atypical sx of ACS

- when to call 911 (do not wait &/or try to drive yourself to the ER)

ACS classic sx include:

midline anterior diffuse chest discomfort

- at rest or provoked by activity that increase cardiac O2 demand

- gradual onset

- lasts > 20 mins

- may:

*radiate (shoulder, arms &/or back or jaw)

*be assoc. w/ diaphoresis or N/V

ACS atypical sx include:

- dyspnea

- weakness

- N/V

- epigastric pain or discomfort

- palpitations

- syncope w/o chest pain

- cardiac arrest

key features of a ______________ can identify & risk stratify a patient w/ ACS

12-lead EKG

what should be obtained & interpreted w/i 10 mins of presentation to the ED?

12-lead EKG

- compare w/ past EKGs

- repeat q 5-10 min if nondiagnostic (1st is usually nondiagnostic)

who provides the treatment guidelines for STEMI, non-STEMI, & percutaneous coronary intervention (PCI)?

american heart association (AHA) & american college of cardiology foundation (ACCF)

what does the general treatment of ACS include?

- hospital admission

- O2

- continuous EKG monitoring

- frequent vitals

- bed rest for 12 hrs (if hemodynamically unstable)

- avoid valsalva maneuver

- adequate pain relief

- revascularization w/ PCI or CABG is usually necessary

- pharmacotherapy

how can the valsalva maneuver be avoided in ACS patients?

prescribe stool softeners routinely

what does pharmacotherapy of ACS include?

- antiplatelets/anticoagulants (possibly fibrinolytics)

- nitrates

- BBs

- ACE-Is

- K+ sparing diuretics

- morphine

- statins

what are the desired outcome in ACS tx?

- early restoration of blood flow to prevent infarct expansion or prevent complete occlusion & MI

- prevention of:

*death

*life threatening ventricular arrhythmias

*other MI complications

*coronary artery reocclusion

- relief of ischemic chest discomfort

- resolution of ST segment & T wave changes on EKG

w/ a STEMI, what is the goal door to needle (fibrinolytics) time?

< 30 mins

w/ a STEMI, what is the goal door to balloon (PCI) time?

< 90 mins

for all ACS, what is the goal door to EKG time?

< 10 mins

as long as w/o contraindications, all ACS patients should receive what meds upon arrival?

aspirin & an ADP-inhibitor

- should also be given SL NTG & O2

as long as w/o contraindications, what should all ACS patients be prescribed at discharge?

- aspirin

- high intensity statin

- BB

- smoking cessation

at discharge, ACS pts w/ EF < 40% w/o contraindications, should also be prescribed an ____________

ACE or ARB

pts should also receive a ________ assessment prior to discharge

LVEF

- bc CHF protocol may also need to be followed if it comes back low enough

PCI (at experienced centers) open _____ of occluded arteries

~90%

fibrinolytics open ____ of occluded arteries

~60%

which has better outcomes if done at experienced centers?

a. PCI

b. fibrinolytics

a. PCI

- due to lower bleeding, stroke, & reocclusion risk

1 multiple choice option

what can be done if PCI is not available on site?

rapid transfer to a PCI center

- as long as door to balloon time (including transport time) is < 120 min

what should be done if PCI is not available w/i 120 mins of 1st medical contact?

treat w/ fibrinolytics

- as long as sx < 12 hrs & no contraindications

STEMI presentation < 3 hrs after sx onset:

highest chance of benefit, substantial myocardial salvage & mortality reduction if treated quickly

when are the mortality benefits of fibrinolytics the highest?

in those presenting < 3 hrs after sx onset

- however, PCI is still preferred (if initiated w/i 120 mins)

STEMI presentation 3-12 hrs after sx onset:

mortality curve plateaus

- fibrinolytics = PCI

- PCI still preferred (if it can be done w/i 120 mins)

STEMI presentation 12-36 hrs after sx onset:

reperfusion benefits are weaker

- some pts may benefit from PCI

- fibrinolytics are NOT beneficial

- may be symptomatic (evidence of continuing ischemia, severe HF, hemodynamic or electrical instability) or asymptomatic (arteriography shows partial or total occlusion w/ low or no collateral flow)

when are fibrinolytics not beneficial or recommended?

if 12-36 hrs after sx onset

what is recommended as an early reperfusion treatment for patients w/ non-STEMI at an elevated risk of death, UA, or MI (including those w/ high risk score, refractory angina, ADHF, other sx of cardiogenic shock, or arrhythmias)?

PCI or CABG

what will patients receive during PCI?

- 2b/3a inhibitors

- aspirin

- ADP inhibitor

- IV anticoagulant

what should all pts that have undergone PCI receive indefinitely?

low-dose aspirin

- + an ADP inhibitor (clopidogrel, prasugrel, ticagrelor) x 1 yr (if drug eluting stent)

STOP ________ therapy in those presenting w/ ACS & provide pt education upon discharge

NSAID

- acetaminophen is okay

what are the initial labs for ACS?

- cardiac biomarkers (troponin)

- CBC

- PT/INR

- aPTT

- electrolytes

- magnesium

- BUN

- SCr

- BG

- lipid

fibrinolytics (thrombolytics)

- PLASE

alteplase (Activase)

reteplase (Retavase)

tenecteplase (TNKase)

all 3 fibrinolytics have similar ________

efficacy

what is a limitation of alteplase (Activase)?

more difficult to administer due to short t1/2

what is an advantage of reteplase (Retavase)?

easier to administer

which fibrinolytic has less non-cerebral bleeding risk & blood transfusions?

tenecteplase (TNKase)

what is an advantage of tenecteplase (TNKase)?

easier to administer in & out of the hospital

- less bleeding risk/blood transfusions

which fibrinolytic is often the DOC in the US?

tenecteplase (TNKase)

all patients that are given a fibrinolytic are also give an _________________________________ to prevent reocclusion

injectable anticoagulant

why is alteplase sometimes called tPA?

bc it was the 1st tissue plasminogen activator on the market

- but tPA also refers to an entire class of drugs

why should tenecteplase not be abbreviated as TNK?

bc it can be confused w/ tPA

- leading to errors

what is the MOA of the fibrinolytics?

"clot busters"

- convert plasminogen into plasmin (a proteolytic enzyme that digests the fibrin meshwork that holds clots together)

are fibrinolytics indicated in non-STEMI?

NO; only STEMI if PCI unavailable (w/i 120 mins)

1 multiple choice option

when are fibrinolytics recommended for STEMI?

in patients presenting w/i 12 hrs of sx & unable to receive PCI w/i 120 mins

are patients presenting w/ STEMI sx for > 12 hrs candidates for fibrinolytics?

NO

1 multiple choice option

are fibrinolytics recommended for use in non-STEMI or UA?

NO; there is not a persistent clot present, so the bleeding risk does not outweigh the benefit

what are the absolute contraindications of fibrinolytics?

* know these, & that all others listed in notes = relative

- active internal bleeding (not included menses)

- previous intracranial hemorrhage at any time

- ischemic stroke w/i 3 months

- known cerebral neoplasm

- suspected aortic dissection

- active bleeding or known bleeding diathesis

- significant closed head or facial trauma w/i 3 months

what are the AEs of fibrinolytics?

- intracranial hemorrhage (0.7-5%)

- reocclusion

- reinfarction

- bleeding

what is the MOA of aspirin?

irreversibly inhibits COX

- which prevents conversion of arachidonic acid to TXA2

what is thromboxane A2 (TXA2)?

a powerful vasoconstrictor & stimulator of platelet aggregation

what is the onset of antiplatelet action w/ aspirin?

very fast

- w/i 30-60 mins

how should aspirin be given for faster onset?

chewed & swallow

- do NOT use enteric coated

- adult 325 mg or chewable baby (4 tabs of 81 mg) can be used

if oral aspirin is not feasible, what should be used?

rectal suppository

what are the possible AEs of aspirin?

- hypersensitivity reactions

- upset stomach/GI discomfort

- GI ulcers

- excessive bleeding (@ any site, due to antiplatelet effects)

is cardiac dose aspirin associated w/ as many of the classic NSAID ADRs (such as, increased BP, fluid retention, or renal impairment)?

NO

1 multiple choice option

what can help alleviate the GI discomfort assoc. w/ aspirin?

take w/ food or use enteric coated

risk of GI ulcers/bleeding w/ aspirin increases w/:

- age

- dose

- duration of therapy

- combination w/ other NSAIDs

does food or enteric coating have any effect on reducing incidence of GI bleeding w/ aspirin?

no

1 multiple choice option

if GI bleeding does occur w/ aspirin, what can be done?

- reduce dose to 81 mg/day

- add PPI

- if above are ineffective, change to ADP inhibitor (if appropriate) & test for h. pylori

cardiac dose aspirin ___________ has been associated w/ an increased risk of clots

withdrawal

1 multiple choice option

_______ may block the antiplatelet benefits of aspirin

NSAIDs

how can you avoid other NSAIDs blocking the antiplatelet effects of aspirin?

administer plain aspirin at least 1 hr before other NSAIDs, so it can bind to platelets first

will taking enteric coated aspirin at least 1 hr before other NSAIDs provide any benefit?

NO

1 multiple choice option

risk of serious bleeding is 20% higher w/ _______________________________ vs. aspirin alone

combo clopidogrel + aspirin

what are the ACS guidelines for use of aspirin in all ACS pts?

325 mg chew & swallow

- followed by 81 mg/day indefinitely thereafter (ACCP recommends 81-100 mg/day)

- if unable to tolerate aspirin, sub an ADP inhibitor indefinitely thereafter

- add PPI if GI bleeding present

what are the ACS guidelines for use of aspirin in ACS pts undergoing PCI?

325 mg chew & swallow

- followed by 81 mg/day indefinitely thereafter (ACCP recommends 81 mg/day)

- dual antiplatelet therapy w/ ADP inhibitor x 1 yr (depending on type of stent placed)

- add PPI if GI bleeding present

if co-administering w/ ticagrelor, do NOT exceed ________ aspirin daily

100 mg

ADP-inhibitors (P2Y12 receptor blockers)

- GREL or - GRELOR

clopidogrel (Plavix) po

prasugrel (Effient) po

ticagrelor (Brillinta) po

cangrelor (Kengreal) IV

which is the only ADP inhibitor that can be given IV?

cangrelor (Kangreal)

- onset: rapid (15 min)

- t1/2: short (<1 hr)

what are the possible AEs of ADP inhibitors?

- minor & major bleeding

- GI disturbance/abdominal pain (take w/ food)

- diarrhea

- rash

- dizziness

- HA

- thrombotic thrombocytopenic purpura (TTP)

- hypersensitivity reactions

which ADP inhibitor carries the highest risk of bleeding?

ticagrelor (> prasugrel > clopidogrel)

_____________ can cause mild, transient dyspnea in 1/3 of patients during the 1st wk of therapy

ticagrelor

when is prasugrel contraindicated?

prior stroke or TIA

- precaution > 75 y/o or weight < 60 kg

what is the effectiveness of ticagrelor reduced by?

daily aspirin dosages > 100 mg

______________ is a prodrug that must be converted to its active form using CYP2C19 & other p450 enzymes

clopidogrel

what are some potential drug interactions w/ clopidogrel?

- some PPIs

- statins

- azole antifungals

- others

clopidogrel loading dose is 300-600 mg unless the patient is > 75 y/o, then what is given?

75 mg loading dose

what is the black box warning assoc. w/ clopidogrel?

PPIs may decrease efficacy (bc they inhibit CYP2C19)

which PPI has some evidence that it is least likely to cause a problem w/ clopidogrel?

pantoprazole (Protonix)

in addition to aspirin continued indefinitely, what are the ACS guidelines for use of ADP-inhibitors in all ACS (STEMI, non-STEMI, UA) w/ PCI?

ticagrelor or prasugrel LD followed by MD w/ clopidogrel (preferred), ticagrelor, or prasugrel for a minimum of 6 months

- DAPT may be 12-30 months

MD =

maintenance dose

LD =

loading dose

DAPT =

dual antiplatelet therapy

in addition to aspirin continued indefinitely, what are the ACS guidelines for use of ADP-inhibitors in STEMI w/ fibrinolytics?

clopidogrel LD

- long term MD x 1 yr w/ aspirin + ticagrelor or other ADP inhibitor

why is clopidogrel the preferred LD in pts receiving fibrinolytics?

bc others have not been studied & may have an increased bleed risk

in addition to aspirin continued indefinitely, what are the ACS guidelines for use of ADP-inhibitors in STEMI & NO reperfusion therapy, non-STEMI or UA w/o PCI?

ticagrelor LD

- followed by DAPT w/ MD x 1 yr

what does the duration of DAPT w/ a MD depend on?

- type of stent used (bare metal, drug eluting, etc)

- lack of stenting

- bleed vs clot risk

- cardiologist on case

IIb/IIIa (2b/3a) inhibitors

IV antiplatelets

abciximab (ReoPro)

eptifibitide (Integrelin)

tirofiban (Aggrastat)

what is the MOA of 2b/3a inhibitors?

block 2b/3a glycoprotein platelet precursors

- which prevents platelet aggregation by all factors, including: collagen, TXA2, ADP, thrombin, & platelet activating factor

does routine use of a 2b/3a inhibitor w/ fibrinolytics improve outcomes?

NO

1 multiple choice option

do the ACS guidelines recommend use of 2b/3a inhibitors in all ACS w/ PCI that did NOT receive dual oral antiplatelet drugs?

yes

1 multiple choice option