Lecture 11,12,13 ACS

Question 1

What are risk factors for ACS?

Answer 1

Nonmodifiable: increasing age, male sex (55-64 years old, vs women 65-74 years), FHx of premature CAD

Lifestyle: smoking, diet, weight, physical inactivity, excessive alcohol use

Med Conditions: HTN, DM, dyslipidemia

Question 2

What is the general pathophysiology of ACS?

Answer 2

plaque forms in coronary artery ⇒ increasing flow limiting stenosis ⇒ stable angina

plaque can rupture ⇒ temporary thrombus ⇒ unstable angina

plaque rupture ⇒ permanent thrombus ⇒ MI

possible death

Question 3

What actually is a ‘plaque’ in ACS, specifically when starting out forming?

Answer 3

has a thin fibrous cap, inflammation contributes to thinning/weakening of fibrous cap, larger cholesterol necrotic core, vulnerable to rupture

usually non-obstructive (<70% of luminal diameter)

Question 4

What happens when a plaque ruptures and clot forms?

Answer 4

rupture exposes lipid core to circulating platelets and coagulation fx

platelet adhesion, activation, aggregation ⇒ formation of platelet plug (platelets dominate in arterial thrombosis)

clotting cascade activation ⇒ formation of fibrin meshwork within and on top of platelet plug

thrombus formation abruptly reduces blood flow and O2 supply = ischemia ⇒ infarction ⇒ necrosis and cell death

Question 5

How does ventricular remodelling occur after an MI, and what systems are involved?

Answer 5

SNS: acutely will increases contractility, HR, and peripheral resistance

over time it will desensitize and downregulate Beta1 receptors = impairment of contractility and cardiac output, ventricular hypertrophy

RAAS: acutely will slow stimulation - Na+ and H2O retention, peripheral vasoconstriction

over time ventricular hypertrophy, myocardial fibrosis, scarring ⇒ impairment of ventricular contraction and elasticity ⇒ thinning of left ventricular wall and development of dilated cardiomyopathy

Question 6

What are common clinical presentations of ACS?

Answer 6

Chest Pain or Discomfort: abrupt persisting for 10 min or longer, squeezing, pressure, crushing, tightness, discomfort rather than pain

not tender

NTG ineffective at eliminating pain

Location: central, sub/retrosternal

radiation - neck, jaw, shoulders, one or both arms, back, epigastrium

Associated Sx: lightheaded, syncope, fatigue, weakness, dyspnea, palpitations, N/V, indigestion, diaphoresis

Atypical Sx: elderly, women, and pt with DM may present with sx not typical

Question 7

What is involved in diagnosis of an MI/ACS?

Answer 7

ECG: may show presence of ST elevation, absence of ST elevation with other ischemic ECG changes - ST segment depression, T-wave inversion

Cardiac Troponin (cTn): detects myocardial injury, highly sensitive, not specific to plaque rupture

to diagnose MI ⇒ at least one + cTn + sx or hx, ischemic ECG changes, imaging evidence of new loss of myocardium

Question 8

What types of ACS are there?

Answer 8

ST-segment elevation myocardial infarction (STEMI) - total occlusion of infarct related artery resulting in necrosis

Non-ST segment elevation myocardial infarction (NSTEMI) - partial occlusion of infarct related artery resulting in necrosis

Unstable Angina (UA) - myocardial ischemia at rest or on minimal exertion in absence of acute cardiomyocyte injury/necrosis

Non-ST elevation ACS (NSTE-ACS) - combo of NSTEMI + UA

Question 9

What is the algorithm for the evaluation and initial management of ACS?

Answer 9

Clinical Suspicion of ACS ⇒ perform 12-lead ECG, ST-segment monitoring, serial cTn levels ⇒ ASA 162-325 mg (chew and swallow) AND/OR NTG spray (up to 3 doses) AND/OR morphine IV prn for refractory pain AND/OR oxygen (if O2 saturation <90%) ⇒ either ST-segment evaluation ACS or Non-ST segment ⇒ if ST-segment ⇒ initiate reperfusion tx - primary PCI, fibrinolysis

if Non-ST segment ⇒ risk stratify - low risk, intermediate-high risk ⇒ for both ⇒ parenteral anticoagulant (UFH, enoxaparin, fondaparinux), ASA 162-325 mg if not already given, P2Y12 inhibitor loading dose

Question 10

How is risk stratification looked at for both STEMI and NSTE/ACS?

Answer 10

STEMI - highest short-term risk of death, consider for emergent reperfusion tx

NSTE-ACS - risk scoring tools are used to assess risk of major cardiac AEs, includes TIMI risk score, GRACE risk score, HEART score

Question 11

What is the difference between reperfusion and revascularization?

Answer 11

Reperfusion: restoration of blood flow within the infarct-related artery in the setting of STEMI, involves PCI and/or fibrinolysis

Revascularization: restoration of the blood flow to the heart when the coronary arteries are blocked or narrowed by atherosclerosis, involves PCI, CABG

Question 12

What are the differences between primary PCI and fibrinolysis regarding their reperfusion abilities for STEMIs?

Answer 12

Primary PCI: performed in a facility able to perform it, is mechanical reperfusion - addition of stent

Fibrinolysis: can be started pre-hospital or ER admin, is pharmacological reperfusion - plasminogen activators are used as clot busters, they increase the conversion of plasminogen to plasmin which binds to fibrin and breaks the strands restoring blood flow

Question 13

How is NSTE-ACS revascularization strategy formed?→dependent on risk

Answer 13

recurrent ischemic event: determined by interaction between pt pre-event status and impact of acute event AND bleeding: increased by intensive antithrombotic tx and invasive management

if they are considered No-Low risk ⇒ ischemia driven approach: no planned PCI

if they are intermediate-high risk ⇒ early invasive approach: diagnostic angiography within 24 hours with intent to perform revascularization if appropriate

Question 14

What is a stent thrombosis, and types?

Answer 14

is the thrombotic occlusion of a coronary stent (may result in ACS)

Acute: within 24 hours after stent insertion - rare complication of procedure

Subacute: within weeks or months after stent insertion - largely preventable with antiplatelet tx ⇒ premature antiplatelet tx discontinuation is biggest independent predictor for this

Question 15

What is in-stent restenosis (ISR), and ways to combat it?

Answer 15

it is a gradual narrowing of the stent lumen due to neointimal proliferation - not a complication but an exaggerated response to vascular injury, results in angina sx, principle cause of lack of long-term clinical success

Drug Eluting Stents (DES): incorporate zotarolimus, everolimus, etc with a time-released polymer ⇒ inhibits neointimal hyperplasia with locally delivered antiproliferative and anti-inflammatory agent reducing risk of this, delay in re-endothelialization lengthens period of risk for subacute stent thrombosis

Question 16

What does the treatment course for ACS look like?

Answer 16

Vulnerable Plaque ⇒ inflammation contributes, larger cholesterol necrotic core ⇒ statins

Plaque Rupture and Clot Formation ⇒ platelet adhesion, activation, and aggregation

clotting cascade activation ⇒ antithrombotics (anticoagulation and DAPT)

Ventricular Remodeling after MI ⇒ SNS chronic hyperactivity, RAAS chronic hyperactivity ⇒ BBs and RAASis

Question 17

What are short term goals for ACS and what drugs are involved?

Answer 17

TEMI: rapid reperfusion to limit infarct size and reduce mortality, initiation of reperfusion strategy, maintain arterial patency ⇒ antithrombotics,, prevent death and other complications, relieve ischemic chest discomfort ⇒ BBs and nitrates

NSTE-ACS: prevent progression of thrombus to occlusion and subsequent infarct expansion, prevent plaque thromboembolization ⇒ antithrombotics

prevent death and other complications, relieve ischemic chest discomfort ⇒ BBs and nitrates

Question 18

What are long term goals for ACS and what drugs are involved?

Answer 18

STEMI and NSTE-ACS: prevent MACEs, prevent recurrent infarction, limit adverse ventricular remodeling, optimize long-term measures to reduce CV risk ⇒ DAPT, statins, BBs, RAASis

Question 19

How is parenteral anticoagulation for ACS managed?

Answer 19

it is used as reperfusion strategy for STEMI and revascularization strategy for ACS but stopped prior to discharge from hospital

uses UFH - Factor Xa and thrombin inhibitor, Enoxaparin - Factor Xa inhibitor, Fondaparinux - Factor Xa inhibitor

Question 20

ASA use for tx in ACS (Role, Dose, PK, interactions, Contra, AE)

Answer 20

Role: all pt with ACS without contra, indefinite tx in most pt with no indication for anticoagulation

Dose: loading dose 162-325 mg PO once (chewed and swallowed), then 81 mg PO QD

PK: onset in <30 min if chewed, <60 min (non-enteric coated), 3-4 hours (enteric coated)

Intx: with other agents that increase bleed risk, NSAIDs prevent it from binding COX-1 which suppress its antiplatelet effects increasing bleed risk

Contra: hypersensitivity,, AE: bleeding, hypersensitivity, dyspepsia, ulcers

Question 21

Clopidogrel use for tx in ACS (Trial, MOA, Dose/PK, Contra, Intx, AE)

Answer 21

Trial: CURE and COMMIT trials

MOA: thienopyridine type prodrug (CYP2C19) that is an irreversible inhibitor of P2Y12

Dose: loading dose 300-600 mg (PCI) PO once, then 75 mg PO QD,, PK: Onset ⇒ 75 mg is 3-5 days, 300 mg is 6-8 hours, 600 mg is 2-3 hours

Contra: active bleeding, severe hepatic impairment

Intx: bioactivated by CYP2C19, inhibitors of this enzyme decrease the active drug levels and inducers increase the active drug levels,, AE: bleeding, rash (up to 6%, pruritic maculopapular)

Question 22

Ticagrelor use for tx in ACS (Trial, MOA, Dose/PK, Contra, Intx, AE)

Answer 22

Trial: PLATO trial

MOA: non-thienopyridine drug that is a reversible inhibitor of P2Y12

Dose: loading dose 180 mg PO once, then 90 mg PO BID

PK: 90 mg in 2-3 days, 180 mg in 1 hour (more potent platelet inhibition)

Contra: active bleeding, severe hepatic impairment, strong CYP3A4 inhibitors/inducers, hx of intracranial hemorrhage

Intx: metabolized by CYP3A4, inhibitors of the enzyme increase levels and vice versa

AE: bleeding, dyspnea (around 14%, happens early), ventricular pauses, increase in uric acid and creatinine

Question 23

How should PPIs and clopidogrel be managed together?

Answer 23

if the patient is in need of a PPI then one that minimally inhibits CYP2C19 like pantoprazole be considered rather than ones like omeprazole and esomeprazole, as the PPIs decrease risk of upper GI bleeding by at least 50% due to interaction

Question 24

Regarding patients who receive PCI in ACS, what is the recommended antiplatelet tx and why?

Answer 24

DAPT with ASA 81 mg QD with either ticagrelor 90 mg BID or prasugrel 10 mg QD over clopidogrel 75 mg QD

greater emphasis on reduction of major CV events and stent thrombosis vs increase in bleeding complications (with clopidogrel) ⇒ can use clopidogrel if patient ineligible for ticagrelor or prasugrel

Question 25

What is the duration of DAPT dependent on in ACS, and how is it affected with DES usage?

Answer 25

refers to the duration of P2Y12 tx,, is dependent on ⇒ the indication for PCI: whether ACS or elective, and the individualized ischemic and bleed risk of the patient regarding DES: the duration of therapy weighs the risk of subacute stent thrombosis/ischemic events against the risk of bleeding

Question 26

What patient factors might warrant a shorter duration of DAPT?

Answer 26

High Bleeding Risk ⇒ active cancer, >/= 75, stroke, bleeding diathesis, previous bleeding or transfusion, planned surgery receiving DAPT, recent trauma or surgery, NSAID or steroid usage, other oral anticoagulant usage, anemia, thrombocytopenia, renal disease, liver disease

Question 27

When might shorter duration DAPT be indicated for usage in ACS?

Answer 27

se for 1-3 months rather than 6-12 months with maintenance single antiplatelet tx in pt undergoing PCI for ACS or elective if ⇒ they are at a high bleeding risk AND don't have any ischemic or bleeding events in the first month should also avoid NSAIDs and use PPIs for pt at risk of GI bleeds,, consider single antiplatelet tx with P2Y12 inhibitor rather than ASA must consider risk of stent thrombosis when contemplating short duration as it may not be suitable for pt undergoing complex PCI with hx of stent thrombosis

Question 28

What patient factors might warrant a longer duration of DAPT?

Answer 28

three lesions/vessels treated/stents deployed >/= 60 mm stent length, bifurcation with 2 stents, CABG, use of atherectomy, CTO PCI, left main PCI

Question 29

When might longer duration DAPT be indicated for usage in ACS?

Answer 29

xtended beyond 1 year (up to 3 years) in pt who ⇒ tolerates 1 year of DAPT without major bleeding event AND aren't at high risk of bleeding pt with clinical features for increased ischemic risk or complex PCI may derive greater + from extended duration should still perform an ongoing assessment of bleeding and ischemic risk at least annually

Question 30

What are some predictors of premature clopidogrel discontinuation?

Answer 30

older pt, less likely to have completed high school, less likely to be married, more likely to avoid health care due to cost, pre-existing CVD, anemia at presentation less likely to have been given discharge instructions regarding meds, less likely to have been referred to cardiac rehab

Question 31

How should statins be used in ACS patients (Indication, initiation, dose, follow-up)?

Answer 31

Indication: should be used in ALL ACS pt without contra,, reduces mortality, recurrent MI, stroke, and need for coronary revascularization Initiation: draw lipid panel within first 24 hours of ACS presentation ⇒ initiate high intensity tx ASAP after hospital admission once pt stable Dose: maximally tolerated dose even those with 'normal' LDL-C ⇒ atorvastatin 80 mg, rosuvastatin 40 mg if intolerant may consider moderate intensity or lower doses of high-intensity Follow-Up: repeat lipid panel in 6-8 weeks to assess for additional lipid-lowering tx

Question 32

For ACS patients, what does the tx regimen look like if they were already taking statins before their ACS?

Answer 32

if they are LLT naive irrespective of LDL ⇒ initiate high intensity high dose if they are on low intensity low dose irrespective of LDL ⇒ change to high intensity high dose if they are on highest tolerated statin already ⇒ is there LDL <1.8? ⇒ if yes then no change needed, if no then add ezetimibe if they are on highest tolerated statin and ezetimibe ⇒ is there LDL <1.8? ⇒ if yes then no change needed, if no then add PCSK9i

Question 33

How should BBs be used in ACS patients (Indication, initiation, dose, AE, length of tx)?

Answer 33

Indication: should be used in ALL ACS pt without contra reduces risk of mortality, MI, angina, and arrythmias Initiation: initiate oral within first 24 hours of presentation UNLESS ⇒ signs of HF, risk for shock or evidence of low cardiac output state, contra (ex. high grade AV heart block, active asthma) Dose: bisoprolol 2.5 mg QD working up to 10 mg QD if possible metoprolol 12.5-25 mg BID working up to 100 mg BID if possible carvedilol 3.125-6.25 mg BID working up to 25 mg BID if possible AE: HF, cardiogenic shock, hypotension, bradycardia Length: if LVEF 40%, low risk and no other indications for one then 1-3 years

Question 34

ow should ACEi/ARBs be used in ACS patients (Indication, initiation, dose, AE, follow-up, length of tx)?

Answer 34

Indication: reasonable for ALL pt after ACS without contra in STEMI ⇒ all pt with anterior location, HF, or LVEF /= 10 mg QD Perindopril 2-4 mg QD work up to 8 mg QD Ramipril 2.5 mg BID work up to 5 mg BID, Valsartan 20 mg BID work up to 160 mg BID AE: hypotension, renal dysfunction, hyperkalemia, dry cough Follow-Up: SCr and K+ in 1-2 weeks following initiation or titration, then every 3-6 months as indicated Length: indefinite, especially if LVEF

Question 35

How should aldosterone antagonists be used in ACS patients (Indication, initiation, dose, AE, follow-up, length of tx)?

Answer 35

Indication: used in pt post-MI already on ACEi + BB ⇒ with LVEF

Question 36

How should NTG be used in ACS patients?

Answer 36

all pt should be prescribed and instructed on appropriate use of this to relieve acute anginal sx PRN ⇒ 0.3 mg tabs/0.4 mg SL spray every 5 minutes up to 3 doses PRN for chest pain

Question 37

How should colchicine be used in ACS patients?

Answer 37

low dose 0.5 mg QD may be considered particularly if other risk fx are insufficiently controlled or if recurrent CVD events occur under optimal tx