Lecture 11,12,13 ACS Flashcards
What are risk factors for ACS?
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
What is the general pathophysiology of ACS?
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
What actually is a ‘plaque’ in ACS, specifically when starting out forming?
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)
What happens when a plaque ruptures and clot forms?
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
How does ventricular remodelling occur after an MI, and what systems are involved?
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
What are common clinical presentations of ACS?
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
What is involved in diagnosis of an MI/ACS?
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
What types of ACS are there?
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
What is the algorithm for the evaluation and initial management of ACS?
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
How is risk stratification looked at for both STEMI and NSTE/ACS?
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
What is the difference between reperfusion and revascularization?
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
What are the differences between primary PCI and fibrinolysis regarding their reperfusion abilities for STEMIs?
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
How is NSTE-ACS revascularization strategy formed?→dependent on risk
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
What is a stent thrombosis, and types?
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
What is in-stent restenosis (ISR), and ways to combat it?
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
What does the treatment course for ACS look like?
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
What are short term goals for ACS and what drugs are involved?
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
What are long term goals for ACS and what drugs are involved?
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
How is parenteral anticoagulation for ACS managed?
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
ASA use for tx in ACS (Role, Dose, PK, interactions, Contra, AE)
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
Clopidogrel use for tx in ACS (Trial, MOA, Dose/PK, Contra, Intx, AE)
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)
Ticagrelor use for tx in ACS (Trial, MOA, Dose/PK, Contra, Intx, AE)
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
How should PPIs and clopidogrel be managed together?
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
Regarding patients who receive PCI in ACS, what is the recommended antiplatelet tx and why?
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
What is the duration of DAPT dependent on in ACS, and how is it affected with DES usage?
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
What patient factors might warrant a shorter duration of DAPT?
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
When might shorter duration DAPT be indicated for usage in ACS?
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
What patient factors might warrant a longer duration of DAPT?
three lesions/vessels treated/stents deployed
> /= 60 mm stent length, bifurcation with 2 stents, CABG, use of atherectomy, CTO PCI, left main PCI
When might longer duration DAPT be indicated for usage in ACS?
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
What are some predictors of premature clopidogrel discontinuation?
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
How should statins be used in ACS patients (Indication, initiation, dose, follow-up)?
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
For ACS patients, what does the tx regimen look like if they were already taking statins before their ACS?
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
How should BBs be used in ACS patients (Indication, initiation, dose, AE, length of tx)?
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% then indefinite, if LVEF >40%, low risk and no other indications for one then 1-3 years
ow should ACEi/ARBs be used in ACS patients (Indication, initiation, dose, AE, follow-up, length of tx)?
Indication: reasonable for ALL pt after ACS without contra
in STEMI ⇒ all pt with anterior location, HF, or LVEF </=40%
in NSTE-ACS ⇒ all pt with LVEF </=40% and those with HTN, DM or stable CKD
reduces mortality, fatal and nonfatal major CV events
Initiation: STEMI ⇒ within first 24 hours to all with anterior location, HF, or LVEF </=40% unless contra
NSTE-ACS ⇒ early initiation within 48 hours of presentation improves survival at 30 days
Dose: enalapril 2.5-5 mg BID work up to 10-20 mg BID
Lisinopril 2.5-5 mg QD work up to >/= 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 </=40%, HTN, DM, or CKD
How should aldosterone antagonists be used in ACS patients (Indication, initiation, dose, AE, follow-up, length of tx)?
Indication: used in pt post-MI already on ACEi + BB ⇒ with LVEF </=40% AND either ex HF or DM AND without renal dysfunction or hyperkalemia
reduces risk of all-cause and CV mortality and improves LVEF
Initiation: within first 14 days following MI, early initiation <7 days sig reduced rates of all-cause mortality, sudden cardiac death, and CV mortality/hospitalization,, Dose: spironolactone 12.5-25 mg QD work up to 25-50 mg QD
Eplerenone 12.5-25 mg QD work up to 50 mg QD
AE: hyperkalemia and renal dysfunction, spironolactone ⇒ gyno, mastodynia, ED, menstrual irregularities
Follow-Up: SCr and K+ in 3 days and 1 week after start or titration, then monthly x 3 months, then every 3 months after,, Length: indefinite if LVEF </=40%
How should NTG be used in ACS patients?
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
How should colchicine be used in ACS patients?
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
