Acute Coronary Syndromes (Part 2) Flashcards
In the setting of stable exertional ischemic heart disease (SIHD) theres an increase in ? which upsets the ?
Increase in myocardial O2 demand which upsets the balance and causes chest pain
In the setting of ACS and atherosclerosis plaque rupture, there’s an acute drop in ?
Acute drop in myocardial O2 supply which upsets the balance and causes chest pain
ACS : Clinical Signs and Sx’s
- Substernal chest pain
-Describe some characteristics
What other signs are there?
-D,N,D,P
-Sense of?
-P,A,L
-WHat kind of heart sounds?
Dull, 15-30 mins, radiates to arms, jaw or back
Dypsnea, Nausea,Diaphoresis, palpitations
-Sense of impending doom
-Pallor
-Anxiety
-Low grade fever
-4th heart sound
-JVD and 3rd heart sound
Cardiac Biomarker Reference Ranges
- Troponin T Gen 5
- CK
- CK-MB
- Cardiac Index
- < 22 ng/mL
- 0-175 IU/L
- 0-2.8 ng/mL (female)
0-4.8 ng/mL (Male) - 0-2.5% –> [CK-MB/CK activity ]*100
General Tx measures for all STEMI and High/intermediate risk NSTE-ACS Pt’s
Admission to ?
Oxygenation if?
Continuous ___
___ control
Frequent ___
__relief
S__
Hospital
if O2 Sat <90%
multi lead ECG monitoring looking for ischemia and arrhythmias
glycemic
vital sign monitoring
pain
stool softeners
TX : STEMI ED
Beginning with chest pain lasting >= 10 mins, what is the pathway for STEMI diagnosis and treatment options?
If chest pain >= 10 mins, do 12 lead ECG within 10 mins , if ST segment elevation —> in ED give MONA (Morphine, oxygen, NTG SL +/- IV, Aspirin or clopidogrel)
—> Heparin IV, +/- Metoprolol IV
–>. Can give P2Y12 inhib, can give statin (If not in ED give later)
-Start reperfusion therapy PCI or Fibrinolysis
Early Pharmacotherapy : STEMI Morphine
-What’s the dose?
-Indicated for?
-AVOID in which patients?
-Caution because?
-Morphine has DDI with?
1-5 mg IV slow bolus every 5-30 mins PRN
-Indicated for chest pain, anxiety, pulmonary edema
-lethargy, hypotension, bradycardia
-may not be able to tell if pt has relief of chest pain or just being blunted by opioid
-clopidogrel
Early Pharmacotherapy : STEMI OXYGEN
Dose?
Indicated for O2 saturation under?
Other uses?
2-4 LPM by nasal cannula
-O2 sat < 90%
-HF
-Dyspnea
Early Pharmacotherapy : STEMI NITROGLYCERIN
-Decreases incidence of __ while using nitrates during?
-What’s the NTG sublingual dose?
-What can be used if pain not controlled? Dose of this?
-What’s an early sign of nitrate tolerance ?
-DONT USE nitroglycerin if SBP is ??? **
-Limit IV nitroglycerin to complicated pt’s with ?
Death, first 24 hrs of care
-0.4 mg every 5 min x 3 doses as BP allows
-IV nitroglycerin . 10 mcg/min IV and titration by 10mcg/min every 5 mins until free of CP or dose related side effects
-Tachyphylaxis
-SBP < 90 mmHg or < 30 mmHg below baseline
-ongoing anginal pain, LV failure, severe HTN
Early Pharma : STEMI ASPIRIN
-Its the most ___ adjunctive therapy for ACS
-ASA DECR ____ in stemi’s
-Dose?
-Cost effective
-Mortality rate
-325 mg (or 4x81 mg = 324 mg) chewed and swallowed as soon as possible
Early Pharma : STEMI HEPARIN
-Exerts direct antiplatelet effects by binding to and inhibiting ___
-Major effect is on interaction between __ and ___
-Initiated in ?
-Continued in cath lab to prevent ___
VWF
Thrombin, antithrombin-III. Inhibs thrombin induced platelet aggregation that initiates UA and venous thrombosis
ED
Immediate thrombus formation at the site of arterial injury during PCI
HEPARIN : DOSING in STEMI bolus and IV
A. If Fibrinolysis ?
B. If primary PCI?
C. If medical management only?
A. 60 units/kg IV bolus . Max 4000 units
12 units/kg/hr IV (max initial rate = 1000 units/hr)
Titration based on APTT (1st APTT at 3 hrs, subsequent q6hrs)
B. 60 units/kg IV bolus, max of 5,000 units
-12 units/kg/hr (max initial rate = 1000 units/hr)
-ACT monitoring in cath lab
C. 60 units/kg IV Bolus (max 5000 units)
-12 units/kg/hr (max initial rate = 1000 units/hr)
-APTT to monitor heparin based on nomogram
Heparin : Monitoring
-What must you monitor?
-What monitoring tests to determine level of anti coag?
-Signs of ?
-recurrent ____
-T
-CBC w/platelet count
-aPTT - outside cath lab , ACT inside cath lab
-bleeding
-ischemia
-thromboembolism
Heparin : Precaution and Side effects
-narrow ___
-Heparin induced _____
-H
-H (rare)
-Reverse anti coagulation by ?
Therapeutic window
Thrombocytopenia can occur after 5+ days of therapy
Hemorrhage
Hypersensitivity reactions (rare)
Stopping infusion +/- administration of protamine. PROTAMINE dose = 1 mg for every 100 units of circulating heparin (t1/2 is 60-120 mins)
EARLY pharmacotherapy : STEMI BETA BLOCKERS
-The benefit would be ?
-Dose?
-Avoid in ?? (5)
-Early (0-12 hrs) administration of Beta blockers within 12 hrs of onset of CP can reduce ?
-Reduction in myocardial workload (DECR HR, BP, myocardial contractility)
- Metoprolol tartrate 5 mg IV q 5 mins up to 3 doses in refractory HTN or ongoing ischemia w/o CI
1.Advanced age (70 yrs and older)
2. Bradycardic (HR < 60 bpm),
3. Hypotensive pt’s (SBP < 120 mm hg)
4. prolonged PR interval ,2nd or 3rd degree heart block
5. active asthma or reactive airway disease
- ventricular arrhythmias, recurrent ischemia, re-infarction, and mortality
If a STEMI patient who is a candidate for reperfusion arrives at a PCI-Capable hospital, what’s the time window by which they must receive primary PCI?
Door 2 Balloon time is 90 minutes
If a STEMI pt is seen at a non-PCI capable hospital, and you want to transfer them to another facility for PCI , what’s the time window by which all of this has to occur?
-If we are unable to transfer our patient within this time limit, what must be started and what is the time limit to begin this tx?
They need to be transferred and start PCI in the facility that is capable within 120 mins or less.
-Fibrinolysis or Thrombolysis must begin within 30 mins of arrival
Fibrinolysis : They increase MVO2 ___ by ___ and allowing for greater blood flow
What are some indications for Fibrinolysis ?
Supply, dissolving the thrombus
- Sx’s of ACS w/an onset within 12 hrs of first medical contact
- ST Segment elevation of at least 1 mm in height in 2 or more contiguous leads, or new or presumed new left bundle branch block
- Anticipated that primary PCI cant be performed within 120 mins of first medical contact
In which situations would we favor thrombolytics and in which situation would we favor PCI?
We favor thrombolytics in aspects of bleeding. PCI causes more major bleeding.
However, Thrombolytics cause more ICH, in this situation we favor PCI
Intracranial Hemorrhage (ICH):
remains the biggest concern with ?
-this is most likely to occur during ?
-Characteristics of pt’s with incr risk of ICH? (5)
-rank the fibrinolytics in terms of most bleeding rate?
Fibrinolytics
-most likely to occur within first 24 hrs
-females, age > 75 yrs old, known cerebral vascular disease, elevated DBP and or SBP, HTN
-Tenecteplase > Reteplase > Alteplase
Absolute CI’s for Fibrinolysis ?
- Active ___ (not including menses)
- Previous ___
- ___ within 3 months (except it happening within 4.5 hrs)
- Known ___ (primary or metastatic)
- Known _____ (arteriovenous malformation)
- Suspected ____
- Significant closed ___ or ____ within 3 months
- ___ or __ surgery within 2 months
- Severe uncontrolled ___ (unresponsive to emerg therapy)
- For streptokinase, prior streptokinase tx within previous ___
- Internal bleeding (not menses)
- Intracranial hemorrhage (ICH) at any time
- Ischemic stroke
- Malignant intracranial neoplasm
- Structural vascular lesion
- Aortic dissection
- Head, facial trauma
- Intracranial, intraspinal
- Hypertension
- 6 months
Check Fibrinolysis dosing on chart and know Tenecteplase
See Chart
Fibrinolysis : Monitor for Side Effects such as? (4)
Consider Fibrinolysis successful if? (3)
- BP
- Bleeding (Hematocrit, Hgb, hematuria, hematemesis, hemoptysis, hematochezia)
- Mental status bc of risk of ICH
- Allergic rxns
- > 50% reduction in ST Segments of the ECG
- Relief of chest pain
- Appearance of reperfusion arrhythmias
Primary PCI :
Transporting pt’s directly from ___ to ___
What should already be started?
Diagnostic angiogram completed will give u which two options?
What are the antithrombotic strategies during PCI?
ED, CATH LAB
Heparin
Continue with PCI or Defer to CABG
- Continue heparin from ED as mono therapy
- Continue heparin and add Cangrelor
- Stop heparin and start BIVALRUDIN + CANGRELOR
- Possible (rare) use of glycoprotein 2b/3a inhibitors added on to one of the above choices during PCI as a means of salvage or part of bailout strategy
PRIMARY PCI : Bivalirudin
-Initiated in __ with ___
-May be used as an alternative to __ +/- __
-It has similar outcomes but less ___
-May reduce ___ after discontinuation to a greater degree than heparin
-Mechanism?
-PRIMARY PCI DOSING?
-Monitoring test?
-When should you discontinue ? If you continue it, whats the dose and how long?
-Caution : reduce dose with ?
Cath lab with PCI
- heparin +/- Glycoprotein 2b/3a inhibitors
-bleeding
-thrombin deactivation
-direct thrombin inhibitor
-LD is 0.75 mg/kg IV bolus , MD 1.75 mg/kg/hr
-ACT
- At the end of PCI or may continue with 1.75 mg/kg/hr x 4 hrs and then 0.2 mg/kg/hr (up to 20 hrs post PCI)
-Significant renal disease
Primary PCI ED or Cath Lab : ADP receptor blockers
- What are the drug classes?
- MOA?
- Prevents transformation of ?
- Leads to less ?
- Thienopyridines / P2Y12 inhibitors (Clopidogrel, prasugrel, ticlodipine ) (Clopidogrel, prasugrel, ticagrelor, cangrelor) ticagrelor and cangrelor are reversible
- Irreversibly inhibit the binding of ADP to its platelet receptor
- Glycoprotein 2b/3a receptor into its active form
- Leads to less platelet aggregation
Kim Check Chart for P2Y12 inhibitors
See Chart
Clopidogrel (Plavix)
-What kind of drug is it?
-Indicated in which states? (3)
-Requires 2 step bio activation with ?
2nd gen P2Y12 antag
NSTE-ACS, medically treated STEMI, fibrinolytic treated STEMI
CYP 450, and CYP 2C19 also plays role
Describe the Clopidogrel and CYP2C19 Polymorphism
If patients have 2 loss of function alleles, for example *2 and *3 , they are unable to metabolize clopidogrel affectively. In these patients, clopidogrel is subtherapeutic and there’s diminished antiplatelet effects.
What drugs inhibit 2C19 and prevent activation of clopidogrel?
-what’s the reccomendation ?
PPI’s
-avoid omeprazole or esomeprazole, use pantoprazole or H2 receptor antags
-use PPI’s only if high risk of GI Bleed
Clopidogrel : pros and cons
PROS : It covers alot of indications, state 5
-It has less ___ compared to prasugrel
- NSTE-ACS (w/ or without PCI)
- STEMI (medical management only)
- Recent MI
- Recent stroke
- Peripheral artery disease
Bleeding
Clopidogrel : CONS
It requires ___ by CYP enzymes
-What can affect its production of active metabolite?
-Which genetic variabilities cause nonresponsiveness?
2 step bioactivation
DDI’s
CYP2C19 polymorphism
ABCB1 gene encoding intestinal transporter
CYP3A4/5 polymorphism
Prasugrel :
What kind of drug?
Indicated for? *****
Its a ___ requiring bioactivation via ____
Lack of ____
Lack of ____
More predictable ___
3rd gen P2Y12 antag
ACS being managed WITH PCI
prodrug , CYP450 (3A4 and 2B6)
PK DDI’s
genetic variability
antiplatelet response
Prasugrel and the Elderly (>=75)
Why is there no net benefit? (2)
Not recc EXCEPT in high risk patient groups such as (2)?
It has more risk for fatal + intracranial bleeding events and symptomatic ICH than clopidogrel.
Diabetes or prior MI where its effect appears to be greater and its use may be considered
DO NOT use Prasugrel in patients with history of ??
However, in patients with NO HX of TIA/Stroke how did prasugrel compare with clopidogrel ?
Transient ischemic attacks (TIA) or stroke (CONTRAINDICATION)
Rate of stroke and ICH LESS than clopidogrel
Prasugrel and Low body weight (<60 kg)
-Listed as an additional ___ for bleeding due to incr exposure to active metabolite when taking 10 mg daily
-No ___
-Consider ___
risk factor
net benefit
5 mg daily
Prasugrel PROS
-How many steps of bioactivation ? using which enzymes?
-More ___ and _____
-Lower rate of ? (4) , especially in pt’s with ?
-More consistent ___
-No signif ____
-Not affected by ___
1 step. 3A4 and 2B6
potent, rapid platelet inhibition
CV death, MI, stroke, stent thrombosis (especially in pt’s with prior MI or diabetes)
antiplatelet response
DDI’s
2C19 polymorphisms
Prasugrel CONS :
- Only indicated in ___ to be managed with ____
- Higher rate of ___ in many pt populations such as ?
- Must hold drug _____ prior to ___
- ACS, PCI
- bleeding, HISTORY OF TIA/STROKE, AGE > 75, Weight < 60
- 7 days, CABG
Ticagrelor (Brilinta ) :
- what kind of drug?
- Indicated for?
- DDI’s such as ?
- It’s ____
- No ___
- has predictable ___
- 4th gen P2Y12 antag (NON Thienopyridine)
- ACS (PCI or non invasive medical management)
- Metabolized by CYP 3A4/5 . PGP substrate and inhib, aspirin
- reversible
- biotransformation
- antiplatelet response
Non-Intracranial fatal bleeding profile favors ?
Intracranial fatal bleeding favors ?
CI in pt’s with ?
PLATO Trial : When u use ticagrelor, what MUST your aspirin dose be ?
Ticagrelor
Clopidogrel
History of ICH
81 mg (maintenance dose)
Ticagrelor associated Dyspnea:
-Most common AE
-Early onset such as ?
-Resolution occurs upon ?
-Pt’s with prior history of CHF, asthma, and COPD ___
< 1 week
d/c of tx (but discontinuation rate is low)
DONT appear more likely to develop dyspnea
What did they witness in the ONSET/OFFSET Study ? (Ticagrelor vs Clopidogrel)
What happens if Ticagrelor dose is missed? Why is this good and bad?
Inhibition of platelet aggregation (IPA) was higher in ticagrelor! Clopidogrel had a LD of 600 vs brilinta’s at 180mg and ticagrelor had IPA much higher from the jump
If Brilinta dose is missed, pt should have same level of IPA as clopidogrel after 24 hrs. Good if pt misses a dose, bad because even though brilinta is “reversible” it still takes a couple of days to reverse its effects !
TICAGRELOR : PROS
- doesnt require ___
- More __ and ___ platelet inhib
- Lower rate of ? (4)
- Can be used for ACS being managed with ___ or ___
- More consistent ___
- Not affected by ?
- bioactivation
- potent, rapid
- CV death, MI, stroke , stent thrombosis
- PCI, meds only
- antiplatelet response
- cyp 2c19 polymorphisms
Ticagrelor CONS :
- Dosed ?
- Cant use in ?
- Caution with ?
- DDI’s?
- twice daily
- ICH pt’s
- advanced lung disease or COPD
- cyp 3a4/5, pgp, aspirin
Comparison of Oral Thienopyridines in at risk pop
See Chart
Kim see chart
Cangrelor (In Cath Lab )
- FDA approved as an adjunct to ___ to reduce periprocedural MI , repeat coronary revasc and stent thrombosis in pt’s who have not been treated with ___ or ___
- Its an ____ (like IV clopidogrel)
- What’s the dose?
- Does it need dose adjustment based on sex, age, renal status, or hepatic function ?
- Common AE’s?
- PK?
- PCI, P2Y12 , GP 2B/3A inhibitor
- IV antiplatelet
- 30 mcg/kg IV bolus f/b 4 mcg/kg/min for at least 2 hrs or for the duration of PCI (whichever is longer)
- No
- Bleeding
- 100% platelet inhibition w/in 2 mins of bolus and return of platelet function within 1 hr after turning off cangrelor
Cangrelor and Transitioning to Oral P2Y12
- When can u give Brilinta 180 mg?
- Prasugrel 60 mg?
- Clopidogrel 600 mg?
- at ANY TIME during cangrelor infusion or immediately after
- immediately after discontinuation of cangrelor
- immediately after discontinuation of cangrelor
Later Pharmacotherapy : STEMI
ACE INHIBITORS INDICATIONS
Name 5
-HF
-HTN (especially in high risk and diabetics)
-AMI (acute phase for high risk, post infarction left ventric dysfunction)
-Nephropathy (especially diabetics)
-Cardiovasc protection
When should you use an ACEI in AMI?
Use within 24 hrs of a suspected anterior wall MI or STEMI associated with clinical HF and those with an LVEF <= 40% in pt’s with no CI’s
Use after first 24 hrs for HTN, LVEF>=40%, DM, CKD
STEMI MED MANAGEMENT (additional tx besides PCI)
-All of the therapy used in __
-What can be continued? How long?
Which P2Y12 inhibs?
ED
-Hep, LMWH, or fondaparinux
Hep for 48 hrs, LMWH for 48 hrs or for duration of hospital stay
Clopidogrel or ticagrelor only
STEMI : CABG
-Usually only determined once what is complete ?
-Continue all therapy used in ED EXCEPT?
-Continue ___
-Surgery often scheduled within?
-After surgery, secondary prevention with?
Diagnostic coronary angiogram
no P2Y12 inhibs prior to surgery
heparin drip
5-7 days
SAPT or DAPT
TX : NSTE-ACS
- NSTE-ACS = ?
- What’s the initial event in unstable angina that differs it from stable?
- Unstable angina doesnt generally produce ___ but ___ does
- Early pharmacother for this is similar to STEMI except ?
- unstable angina or NSTEMI
- reduction in coronary blood flow rather than an increase in MVO2
- cardiac biomarkers, NSTEMI
- dont use fibrinolytics
-risk assessment strategy to drive NSTE-ACS management
NSTE-ACS Risk Stratification
- What do you do if your pt is high risk?
- Low risk?
- You would do the same drugs in the ED as STEMI, but u would get them into the cath lab for early invasive approach. But, there’s no 90 minute time limit, u can get them in the next morning. From there, do diagnostic angiogram, then decide primary PCI, Med management, or CABG
- Ischemia driven approach , can just treat with medicine and further work them up to see if u wanna go to cath lab or not
TIMI Risk Score for NSTE-ACS
List 7
-Note, they get 1 point for each risk
Age >= 65 yrs
> =3 CAD risk factors
Known CAD (>= 50% stenosis)
Aspirin use in past 7 days
Severe angina in last 24 hrs
Elevated cardiac markers
ST deviation >= 0.5 mm
TIMI SCORES
For the following , state what their risk is and what the management strategy would be?
- 1-2
- 3 or 4
- 5,6,7
- Low risk, admit for med management w/non invasive stress test
- Medium risk.
biomarkers (-) medical management w/stress testing or imaging
Biomarkers (+), multiple risk factors, opt for early invasive w/PCI
- High risk, urgent PCI within 12-24 hrs
Review : Early PharmTher in NSTE-ACS
- MONA?
- Anticoag?
- Additional agents?
- Morphine, oxygen, SL nitroglycerin +/- IV if needed , aspirin (clopidogrel if aspirin allergic)
- Heparin IV, LMWH, Fondaparinux
- Metoprolol IV, P2Y12 inhib, statin
NSTE-ACS in ED : Anticoags
- UFH (see chart for dosing)
-Can be used for both __ and ___ approach **** - Enoxaparin (Dosing on chart)
-Generally reserved for? - Fondaparinux
-Generally reserved for?
- early invasive, ischemia driven
- ischemica driven approach
- ischemia driven approach
Antiplatelet agents : P2Y12 inhibs
-During PCI use these agents? (4)
-During non invasive med management use these agents only (2)
When should u use CCBs?
Dont use verap and Diltiazem in ?
Which is more useful in NSTE ACS?
Clopidogrel, ticagrelor, prasugrel, or cangrelor
Clopidogrel or ticagrelor
Can sub for beta blocker if CI’s for Beta blockers
LV dysfunction or pulm edema
Diltiazem, reduces reinfarction and refractory angina
Secondary Prevention after MI :
What are some modifiable RF that can be controlled?
What should we be aiming to prevent ? (3)
Smoking, BP, lipids, diabetes, physical activity, weight, diet, stress
prevent devel of systolic HF, recurrent MI and stroke, death!
Secondary Prevention :
- Aspirin should be given ___. Doses?
- Rivaroxaban??
Exclusion?
Wait until DAPT complete and then add on riva to __ if desired
- indefinitely. Doses 81-162 mg PO daily, need to dose aspirin <100 per day when using w/brilinta
- pt’s already receiving aspirin + P2Y12 inhibitor
- aspirin
If you have increased ischemic risk or incr risk of stent thrombosis, what duration of DAPT may u favor?
What factors contribute to Incr isch risk vs risk stent thromb?
LONGER DURATION DAPT
- Advanced age, acs presentation, mult prior mi’s, extensive CAD, DM, CKD
- acs presentation, DM, LVEF < 40%, greater stent length, stent underdizing etc
If you have incr bleeding risk what duration of DAPT may you favor?
What factors contribute to this?
SHORTER DURATION
history of prior bleeding, oral anticoag therapy, females, advanced age, low body weight, ckd, DM, anemia, chronic steroid or nsaid therapy
Secondary Prevention : beta blockers
When should u give for a year vs indefinitely ?
Titrate therapy to reduce resting HR to?
Allow exercise HR <= 20 bpm higher than ?
Maximize dose and avoid in which pt’s?
Year or up to 3 yrs : all pt’s w/o CI’s following an ACS event
-in pt’s with LV dysfunction (EF<40%) with or w/o HF sx’s
-50-60 bpm
resting HR or 100 BPM
ISA
2ndary Prevention ACEI/ARB
-All patients with?
Helps prevent?
Avoid in ?
LVEF <= 40%, stable ckd, DM, HTN, or large anterior wall MI with unknown LVEF
remodeling of LV
Hypotension, renal failure, hyperkalemia
2ndary Prevention : Anti HLD drugs
Lipid panel should be assessed within ?
Post ACS pt’s are in “Clinical ASCVD Group”
- Very high ASCVD use ?
- ASCVD not v high use?
24 hrs
- High intensity or maximal statin
- Age <=75 : high intens
Age > 75, mod or high inten statin or continuation of high intens statin
High inten : Lipitor 40-80 mg, Rosuvastatin 20-40 mg
Mod inten : Lipitor 10-20 mg
Crestor 5-10 mg
Aldosterone Receptor Antags
Name 2
When should they be considered?
- Spironolactone or eplerenone
- In first 2 wks following an MI in pt’s already receiving an ACEI who have an EF <= 40% and either HF sx’s or diagnosis of diabetes
WHat’s the Spironolactone dose?
When may you incr dose to 50 mg po daily ?
When may you decr dose to 25 mg po every other day?
25 mg PO DAILY
8 weeks if pt shows improvement in signs of HF and no hyperkalemia
if hyperkalemia present after dose initiation
Eplerenone
Dose?
Minimal____
25 mg po daily
Gynecomastia
