Acute Coronary Syndrome Flashcards
Characteristic symptoms of STEMI?
Worsening pain/pressure in chest; may be accompanied by radiation.
Caused by total coronary artery occlusion.
Objective findings of STEMI?
ST-segment elevation > 1mm + positive biomarkers (troponin I or T elevation)
Characteristic symptoms of unstable angina and NSTEMI?
Partial coronary artery occlusion.
Pressure-type chest pain occurring at rest or with minimal exertion.
Pain may present w/ diaphoresis, dyspnea, nausea, abdominal pain, or syncope.
Objective findings for Non-ST Elevation ACS Unstable Angina?
ST-segment depression, T-wave inversion, or transient/non-specific ECG changes
No positive biomarkers for cardiac necrosis (no myocardial injury)
Objective findings for NSTEMI?
ST-segment depression, T-wave inversion, or transient/non-specific ECG changes
Positive biomarkers (troponin I or T elevation) -myocardial injury has occurred
What are the 2 methods to restore patency in infarcted-artery during STEMI?
STEMI requires urgent revascularization with:
1. Percutaneous coronary Intervention (PCI) - preferred
2. Drug therapy via fibrinolytics (Lytic therapy)
When is fibrinolytic therapy indicated in STEMI?
For pts when PCI cannot be done w/i 120 min.
Must give fibrinolytic within 30 min from door-to-needle
Goal of NSTE-ACS treatment?
Prevent total occlusion of artery. Control chest pain and other symptoms
What are the 2 methods to treat NSTE-ACS?
Treat based on risk (TIMI or GRACE scores used to asses risk)
Can treat with:
1. Early invasive strategy (Interventional approach)
- Ischemia-guided strategy (conservative method using medications)
What is early invasive strategy and when is it used in NSTE-ACS?
Early invasive strategy: diagnostic angiography with intent for revascularization.
Indicated for: refractory angina, hemodynamic/electrical instability
Note: Invasive therapy superior to ischemia-guided therapy (lower rates of recurrent UA, hospitalization, MI and death) in those with risk features:
1. Age >70 yo,
2. Previous MI/revascularization,
3. ST deviation,
4. HF, LVEF <40%,
5. High TIMI or GRACE scores,
6. Elevated troponins,
7.Diabetes.
Who is Early invasive therapy in NSTE-ACS NOT indicated for?
Not for serious comorbidities/CIs to procedures (ex. hepatic, renal, pulmonary failure, cancer)
Risk outweighs benefit of revascularization
Who can receive ischemia-guided therapy in NSTE-ACS?
- Low risk score (TIMI 0 or 1, GRACE <109)
- Acute chest pain with low chance of ACS + troponin negative (preferred for low-risk women)
List initial anti-ischemic and analgesic therapies for Acute coronary syndrome? (MONA-B). Give dosing, if possible.
M- morphine (or other narcotic analgesic)
*Morphine 1-5 mg IV Q5-30 min
* Pro: analgesia, decreased pain-induced sympathetic/adrenergic tone, slows absorption of antiplt therapy
O- Oxygen
* Consider if SaO2 <90%, respiratory distress, or high-risk features of hypoxemia
*Pro: attenuate anginal pain secondary to tissue hypoxia
*Giving supp. O2 w/o depressed SaO2 associated w/ increased morbidity and mortality
N- Nitroglycerin
*NTG spray or SL tab (0.3-0.4 mg) Q5min up to 3 doses to relieve acute chest pain
*Call 911 if pain not relieved after 1 dose
*Use IV NTG w/i 48hrs for persistent ischemic chest pain, HF, HTN
*Dose: IV NTG 5-10 mcg/min; titrate to chest pain relief or max 200 mcg/min
*Facilitates coronary vasodilation; may help in severe cardiogenic pulmonary edema
A- Aspirin
*Aspirin chewable 162-325 mg x 1 dose
*If aspirin allergy: clopidogrel
*Pro: MORTALITY REDUCING TX, inhibits plt activation
B- Beta-blocker
*Pro: decrease myocardial ischemia, reinfarction, and frequency of dysrhythmias; increase long-term survival
*Start w/i 24 hrs in pts w/o signs of HF or other contraindications to B-blockade (PR interval > 0.24 sec, 2nd/3rd degree heart block, active asthma, reactive airway disease)
*Continue in NSTE-ACS pts w/ normal LV function
* In stabilized HFrEF, use metoprolol succ, bisoprolol, carvedilol
* IV B-blocker may harm pts w/ risk factors for shock (Age >70 yo, HR >110 bpm, SBP <120 mmHg)
When is nitroglycerin contraindicated in ACS?
- Sildenafil or vardenafil use w/i 24 hours
- Tadalafil use w/i 48 hrs
- SBP <90 mmHg or >30mmHg below baseline
- HR <50 bpm
- HR >100 bpm in absence of symptomatic HF
- Right ventricular infarction
Which combination of therapy classes should be initiated in all pts w/ NSTEMI and NSTE-ACS?
All pts should get antiplatelet and anticoagulant therapy - Mainstay of ACS management
-Aspirin + P2Y12 receptor antagonists (+/- GP 2b/3a inhibitors in some pts)
List allowed antiplatelet strategies for NSTE-ACS Ischemia-guided treatment?
- Aspirin +
- Clopidogrel or ticagrelor +/-
- GP 2b/3a inhibitor
List allowed antiplatelet strategies for NSTE-ACS Invasive treatment?
- Aspirin +
- Clopidogrel or ticagrelor or prasugrel +/-
- GP 2b/3a inhibitor
When can ticagrelor and prasugrel be used over clopidogrel in early invasive NSTE-ACS?
For low bleeding risk pts
List allowed antiplatelet strategies for STEMI going to primary PCI?
- Aspirin +
- Clopidogrel or ticagrelor or prasugrel +/-
- GP 2b/3a inhibitor
List allowed antiplatelet strategies for STEMI + fibrinolytic treatment? What fibrinolytics can be used?
- Aspirin +
- Clopidogrel +/-
*Pre-PCI after fibrinolytic: 300 mg LD w/i 24hr of event; 600 mg if >24hr after tx - GP 2b/3a inhibitor
Fibrinolytics
1. Alteplase
2. Reteplase
3. Tenecteplase
When is GP 2b/3a inhibitor used for ACS management?
In pts w/ high-risk features (ex. elevated troponin) not adequately pre-treated w/ clopidogrel or ticagrelor
Length of therapy for patients receiving DAPT after-ACS?
At least 12 months for all pts getting aspirin + P2Y12 inhibitor
Doses of aspirin for pts w/ initial ACS presentation, undergoing PCI, after ACS?
Class I rec: all pts get aspirin
Initial presentation: 162-325 mg
Undergoing PCI: 81- 325 mg
After ACS: 81 mg administered indefinitely
How is choice for oral P2Y12 inhibitor choice made?
Class I rec: all pts get P2Y12 inhibitor
Choice of P2Y12 made based on ischemia-guided vs. early invasive treatment.
Which P2Y12 inhibitors are preferred in ischemia-guided therapy?
Clopidogrel
Ticagrelor
Which P2Y12 inhibitors are preferred in early invasive therapy?
Clopidogrel
Ticagrelor
Prasugrel
When is prasugrel contraindicated for use?
- History TIA or stroke
What is a drug-drug interaction consideration that affects the efficacy of ticagrelor?
Efficacy decreased in higher doses of aspirin (dose >300 mg daily) vs. lower doses (doses <100 mg daily)
When is ticagrelor chosen over clopidogrel in NSTE-ACS or STEMI?
Pts treated w/ early invasive strategy or coronary stenting
When is prasugrel chosen over clopidogrel in NSTE-ACS or STEMI?
Pts undergoing PCI who are not at high bleeding risk complications and have no history of TIA/stroke
*NOTE: ISAR-REACT 5 trial: prasugrel superior to ticagrelor in reducing ischemic endpoints w/o increasing bleeding risk in ACS pts undergoing PCI
Dosing of P2Y12 inhibitors given before PCI?
- Clopidogrel 600mg LD, 75mg daily
- Prasugrel 60mg LD, 10mg daily
- Ticagrelor 180mg LD, 90mg BID
From ACC/AHA and NSTE-ACS guideline recs
Dosing of P2Y12 inhibitors for NSTE-ACS pts treated w/ early invasive or ischemia-guided therapy?
- Clopidogrel 600mg LD, 75mg daily
- Ticagrelor 180mg LD, 90mg BID
When is the maintenance dose of prasugrel decreased?
Prasugrel 5mg used if:
* Weight <60 kg
* Age >/= 75yo
Which P2Y12 inhibitor is vs. is NOT a pro-drug and have reversible/irreversible platelet binding?
Clopidogrel, prasugrel
* Prodrug
*Irreversible platelet binding
Ticagrelor
*Not prodrug
*Reversible, non-competitive binding
Which P2Y12 inhibitor has drug-drug interactions w/ CYP 2C19?
Clopidogrel
Box warning: 2C19 genetic polymorphism
PPIs inhibit 2C19 (avoid using clopidogrel + esomeprazole/omeprazole)
Discuss relevant drugs interactions with ticagrelor.
- Strong 3A4 inhibitors increase TIC concentrations
- Strong 3A4 inducers decrease TIC concentrations (do not exceed simvastatin or lovastatin 40mg)
- Limit aspirin to <100mg daily
- Monitor digoxin concentrations
- Monitor in asthma and bradycardia
Discuss relevant drugs interactions with prasugrel.
No clinically significant drug interactions
What are the surgery hold times for P2Y12 inhibitors?
Clopidogrel, ticagrelor- 5 days
*Emergency CABG: hold at least 24hrs to minimize bleed risk
Prasugrel - 7 days
Contraindications for individual P2Y12 inhibitors?
- Clopidogrel
- Active bleeding (NOTE: clopidogrel has less bleeding risk PRA and TIC with standard dosing)
- Prasugrel
- Active bleed, TIA, CVA (cardiovascular accident)
- Ticagrelor
*Active bleed, ICH, severe hepatic disease
Potential use for cangrelor?
Cangrelor- IV P2Y12 inhibitor w/ rapid onset and offset
Used in PCI only for those who can’t get oral P2Y12
Potential use: bridge therapy after stopping oral P2Y12 inhibitors in high-risk pts undergoing CABG
Note: onset of clopidogrel, prasugrel is delayed when co-administered w/ cangrelor; cangrelor may preferentially bind P2Y12 and prevents irreversible inhibition w/ CLO and PRA’s active metabolites. Therefore, don’t give CLO or PRA until after stopping cangrelor infusion.
Cangrelor dose?
Dose: 30 mcg/kg bolus, 4 mcg/kg/min
Eptifibatide (Integrilin) dosing in ACS with or without PCI?
PCI: 180 mcg/kg IV bolus x 1 (10 min apart), 2 mg/kg/min started after 1st bolus dose for 18-24 hrs
*Double bolus in STEMI and NSTE-ACS PCI
Without PCI: single dose bolus above; uncertain benefit in pts adequately treated w/ P2Y12 inhibitor
Renally dose adjust:
*CrCl <50 mL/min: reduce dose by 50%
* CI: hemodialysis
Tirofiban (Aggrastat) dosing in ACS with or without PCI?
PCI: 25 mcg/kg IV over 3 min; 0.15 mcg/kg for 15 hour
Renally dose adjust:
*CrCl <60 mL/min: reduce dose by 50%
Benefit of adding GP 2b/3a inhibitor to aspirin?
Benefits those w/ high-risk features (elevated biomarkers, diabetes, undergoing revascularization) and inadequate pre-treatment w/ CLO or TIC
Can UFH + GP 2b/3a be used together?
Class 2a rec, 2014 NSTE-ACS guideline
It is reasonable to give GP 2b/3a Inhibitors to high-risk pts w/ NSTE-ACS treated w/ UFH and adequately pre-treated w/ CLO or TIC.
GP 2b/3a inhibs should be used in combo with heparin (either UFH or LMWH) or used provisionally w/ bivalirudin.
What are common adverse effects of GP 2b/3a inhibitors? (List 3)
- Bleeding (1.4%-10.6%)
- Renally dose adjust (eptifibatide, tirofiban are small molecules) to decrease bleed risk
- Thrombocytopenia (monitor Hgb/Hct)
*Giving w/ UFH doesn’t increase thrombocytopenia risk
What is the role of anticoagulant use in ACS?
Anticoagulant should be given to ALL pts w/ ACS in addition to antiplatelet therapy.
*Reason: reduce risk of intracoronary and catheter thrombus formation
*Anticoagulants typically used in the procedural setting
Anticoagulants increase bleeding risk (must monitor)
List available options of anticoagulants for STEMI (PCI).
UFH
Bivalirudin
List available options of anticoagulants for STEMI w/ fibrinolytic therapy.
UFH
Enoxaparin
Fondaparinux
When are fibrinolytics preferred in STEMI treatment? Duration of therapy for anticoagulants?
Fibrinolytics preferred when PCI cannot be done w/i 120min of first medical contact. Goal for fibrinolytic: door-to-needle time <30 min.
Those who get fibrinolytics should be on anticoagulation for at least 48 hrs w/ IV UFH or IV/SQ enoxaparin during hospitalization, up to 8 days (preferred) or IV/SQ fondaparinux during hospitalization, up to 8 days.
List available options of anticoagulants for NSTE-ACS, early invasive strategy.
UFH
Enoxaparin
Bivalirudin
List available options of anticoagulants for NSTE-ACS, ischemia-guided strategy.
UFH
Enoxaparin
Fondaparinux
List monitoring parameters for unfractionated heparin (UFH).
aPTT or ACT, Hgb/Hct, Platelet count
Adjust dose based on activated partial thromboplastin time (aPTT) or activated clotting time (ACT).
What is the dose of UFH in NSTE-ACS?
Bolus 60 un/kg (max 4000 un)
Infuse starting at 12 un/kg/hr (max 1000 un/hr)
Continue for 48 hrs or until PCI
What is an advantage of using UFH in ACS?
UFH is not renally cleared, so can be used safely in renal impairment pts.
List monitoring needs for Enoxaparin and Fondaparinux?
Monitor Hgb, Hct, platelet count
Require SCr to calculate CrCl for dosing
Does not require routine anti-Xa monitoring
Enoxaparin dose for NSTE-ACS?
1 mg/kg SC Q12hr for 24-48 hrs or until PCI or throughout hospitalization (up to 8 days)
Optional: 30 mg IV bolus in ???
Enoxaparin dose in STEMI + PCI?
30 mg IV bolus, then 1 mg/kg SQ Q12hr (NOT TO EXCEED 100 mg on 1st two doses)
If >75yo: omit bolus, then 0.75 mg/kg SQ Q12hr (not to exceed 75mg on 1st two doses)
Enoxaparin dose in ACS for pts w/ CrCl <30 mL/min?
1 mg/kg SQ daily
Clinical pearls for Fondaparinux use (1. class 2. half-life 3. monitoring 4. contraindications)
- Factor Xa inhibitor
- Longest half-life anticoagulant (17 hrs)
- Monitor Hgb, Hct, platelet count
Require SCr to calculate CrCl for dosing
Does not require routine anti-Xa monitoring - Contraindicated in CrCl <30 mL/min
*No increased risk of HIT
*NOT used as the sole anticoagulant during PCI
Advantage of using bivalirudin when other anticoagulants cannot be used in PCI?
Can be used in history of/suspected HIT
Monitoring (labs) needed for bivalirudin?
Monitor SCr (to renally dose adjust), Hgb, Hct, platelets; Note: does not need monitoring for adjustments during PCI
Dosing for bivalirudin during early invasive strategy, PCI, STEMI +/- PCI and for CrCl <30 mL/min.
(1) Early invasive strategy/NSTE-ACS: 0.1-mg/kg LD followed by 0.25 mg/kg per hour (only
in patients with planned PCI), continued until diagnostic angiography or PCI
(2) PCI dosing: 0.75-mg/kg intravenous bolus, 1.75 mg/kg/hour intravenously continued
throughout the procedure (D/C at end of PCI or cont up to 4hrs after procedure); hold UFH 30 min before giving bivalirudin
(3) STEMI +/- PCI: 0.75 mg/kg IV, then 1.75 mg/kg/hr IV
(4) CrCl <30 mL/min: 1 mg/kg/hour or Hemodialysis: 0.25 mg/kg/hour
Can extend duration of infusion for up to 4 hours after procedure for prolonged antiplatelet protection
When is anticoagulant therapy discontinued for PCI?
D/C after PCI unless there is compelling reason to continue
Fondaparinux dosing in NSTE-ACS, STEMI +/- PCI?
NSTE-ACS: 2.5mg SQ daily
STEMI +/- PCI: 2.5mg IVB, then 2.5mg daily
Note: do not use as sole anticoagulant in PCI; must use with enoxaparin or GP 2b/3a + enoxaparin
List recommended anticoagulants when fibrinolytics are used in reperfusion strategy?
UFH
Enoxaparin
Fondaparinux
Alteplase dose in fibrinolytic therapy for pts <67kg vs. >67kg?
- < 67kg: 15mg IVP over 1-2 min, then 0.75 mg/kg IV over 30 min (max 50 mg), then 0.5 mg/kg (max 35 mg) over 60 min
- > 67kg: 15 mg IVP over 1-2 min, then 50 mg over 30 min, then 35mg over 1 hr (max total dose 100mg)
Reteplase dose in fibrinolytic therapy?
10un IVP, repeat 10un IV in 30 min
Tenecteplase dose in fibrinolytic therapy?
<60 kg: 30mg IVP
60-90 kg: 35mg IVP
70-79 kg: 40mg IVP
80-89 kg: 45mg IVP
>90 kg: 50mg IVP (~0.5 mg/kg)
List absolute contraindications for fibrinolytic therapy in ACS (8).
- Prior hemorrhagic stroke
- Ischemic stroke w/i 3 mo
- Intracranial neoplasm, ateriovenous malformation
- Active internal bleeding
- Aortic dissection
- Facial trauma or closed-head trauma in past 3 mo
- Intracranial/instraspinal surgery w/i 2 mo
- Severe uncontrolled HTN (unresponsive to emergency tx)
Duration of DAPT therapy after ACS?
At least 12 months
-DAPT reduces mortality regardless of stent placement
Continue aspirin 81mg indefinitely in ALL pts
Duration of DAPT with ischemia-guided therapy? Available DAPT treatments?
Up to 12 months
Give Aspirin + clopidogrel 75 mg daily OR ticagrelor 90mg daily
Duration of DAPT after PCI treatments? Available DAPT Treatments?
At least 12 months
Aspirin + CLO 75 mg daily, PRA 10mg daily, or TIC 90mg daily
When should early discontinuation of DAPT be considered? Duration?
Consider shorter duration in stable ischemic heart disease who have undergone PCI with ELECTIVE stent place’t
Duration: 6 months for elective PCI
Note: generally shorter duration DAPT for lower ischemic risk and high bleeding risk; longer-duration for higher ischemic risk and lower bleed risk
Give w/ PPI to reduce GI bleed risk in DAPT
When is long-term DAPT, beyond 12mo, a consideration?
When pts are at higher ischemic risk w/ lower bleeding risk
Note: continued DAPT is not associated w/ decreased CV or total mortality
When DAPT is given beyond 12 mo, what is the ticagrelor dose that can be used?
1 year DAPT w/ ticagrelor 90mg BID, then reduce to TIC 60mg BID
Who gets Beta-blockers treatment? Duration to give?
Indicated in all patients unless contraindicated
Initiate w/i first 24 hrs if possible. If not, re-evaluate to start before discharge
Continue for at least 3 yrs when EF >40%
Continue indefinitely for EF <40%
Who gets ACE-i (or ARB) after ACS? Contraindications (List 3)?
Indicated in ALL pts w/ LVEF <40%, HTN, DM, or stable CKD
CI: hypotension, pregnancy, bilateral renal artery stenosis
Who gets lipid-lowering therapy after ACS? When should it be started? What is the goal LDL level/reduction?
Give high-intensity statins to all pts after ACS
Start w/i first 24 hours
Goal: LDL <70 mg/dL
When should non-statin therapy be considered in pts who need lipid-lowering post-ACS?
Consider in high-risk pts when statins have <50% reduction in LDL or in statin-intolerant pts
In high-risk pts start ezetimibe or PCSK9 inhibitors + statin to reduce CV end points
Preferred agents to treat pain after ACS?
Acetaminophen
Non-acetylated salicylates
Tramadol
Narcotics
2nd line: Non-selective NSAIDs (ex. naproxen), IF initial therapy is insufficient
*Monitor: HTN, edema, worsening renal function, or GI bleed
Non-preferred agents for pain management? Why?
Avoid NSAIDs and selective COX-2 inhibitors- D/C at time of presentation bc may be associated w/ increased risk of major CV events.
Antiplatelet recommendations in patients going to CABG.
1. Should aspirin be discontinued?
2. Elective CABG- when should P2Y12 inhibitor be discontinued?
3. Urgent CABG- when should P2Y12 inhibitor be discontinued?
4. Pts referred for CABG- when should GP 2b/3a inhibitors be discontinued?
- No, don’t D/C aspirin. Continue pre-operatively. Aspirin 81 mg -325 mg.
- D/C clopidogrel and ticagrelor 5 days, D/C prasugrel 7 days before CABG
- D/C CLO and TIC for at least 24hrs to reduce risk major bleeding
- D/C Eptifibatide and tirofiban at least 2 hrs pre-surgery
What is the consensus on using triple therapy in A.fib pts undergoing PCI?
Triple therapy: low-dose ASA + P2Y12 inhibitor + anticoagulant- increases bleeding risk; use should be limited to 1-3 months if used beyond hospital discharge
*D/C aspirin at time of discharge or cont. 1-3 mo.s depending on risk
New AF guidelines prefer P2Y12 inhibitor + anticoagulant (DOAC [preferred] or warfarin)
What is the preferred P2Y12 inhibitor in A.fib pts undergoing PCI? When should tx be D/C’d?
Clopidogrel is preferred, but can use TIC in high ischemic/thrombotic and low bleeding risk (AVOID prasugrel)
D/C antiplt therapy at 1 year in most pts
Which direct antithrombin inhibitor is preferred in Age >75yo with ACS?
Bivalirudin»_space;> GP 2b/3a inhibitor + UFH - similar efficacy but less bleed risk
