Therapeutics of Coronary Artery Disease Flashcards
pathophysiology and diagnosis of a STEMI
- Total Occlusion of Coronary Artery -> Unstable plaque causing infarction
- EKG Manifestations: ST segment elevation, NEW left bundle branch block (LBBB)
- Signs/Symptoms: Chest pain, Intense sweating, N/V
- Presence of biomarkers
patients who are candidates for PCI
- First medical contact device time ≤ 90
- Superior to fibrinolytic therapy if availability of skilled interventional cardiology department
- High Risk of Mortality: Cardiogenic shock or severe HF must get PCI right away
- High Bleed risk
- Diagnosis of STEMI in doubt
patients who are candidates for Fibrinolytics
- Administer within 30 min of arrival if first medical contact device time > 120 min
- More appropriate option in institutions with lack of availability of skilled interventional cardiology department
- Low bleed risk
pharmacotherapeutics for PCI
- antiplatelet
- anticoagulation
What are the antiplatelets for PCI?
- ASA (if not already given)
- P2Y12 receptor inhibitor
- GP IIb/IIIa Inhibitors
P2Y12 receptor inhibitors for PCI
- Clopidogrel
- Prasugrel
- Ticagrelor
- Cangrelor
Clopidogrel dose for PCI
600 mg LD
Prasugrel dose for PCI
60 mg
Ticagrelor dose for PCI
180 mg
Cangrelor dose for PCI
30 mcg/kg IV bolus prior to PCI followed immediately by an infusion of 4 mcg/kg/minute continued for at least 2 hours or for the duration of the PCI
What are the anticoag therapies for PCI?
- UFH
- Enoxaparin
- Fondaparinux
- Argatroban
- Bivalirudin
UFH dose for PCI and Fibrinolysis
- After PCI, a weight-adjusted, continuous, IV infusion is administed for 48 hours or until revascularization
- 12 U/kg/hour (maximum 1000 U/hour)
- aPTT of 1.5 to 2.0 times control
- Drug of choice when renal function is unknown
Enoxaparin dose for PCI and Fibrinolysis
- IV bolus, followed in 15 minutes by SQ injection for the duration of hospitalization, up to 8 days or until revascularization
- If age < 75 years: 30-mg IV bolus, followed in 15 min by 1 mg/kg SQ every 12 hours (maximum 100 mg for the first 2 doses)
- If age ≥ 75 years: no bolus, 0.75 mg/kg SQ every 12 hours (maximum 75 mg for the first 2 doses)
- Regardless of age, if CrCl < 30 mL/min: 1 mg/kg SQ every 24 hours
- Consider using this in pts who has history of HITT
Fondaparinux dose for PCI and Fibrinolysis
- NOT recommended as sole anticoagulant for PCI
- Increased risk of catheter thrombosis when used as monotherapy
- Contraindicated in patients with CrCl < 30 mL/min
- Consider using this in pts who has history of HITT
Argatroban use for PCI and Fibrinolysis
- Useful when anticoagulation needs to be extended past PCI
- Dose adjust in hepatic dysfunction
- Useful option in patients with renal dysfunction
Bivalirudin dose for PCI and Fibrinolysis
- Monotherapy anticoagulation in preference to the combination of UFH and a GP IIb/IIIa receptor antagonist
- Monotherapy anticoagulation
- 0.75-mg/kg IV bolus, then 1.75–mg/kg/hour IV infusion
- if CrCl < 30 ml/min = 1 mg/kg/hour
- Consider using this in pts who has history of HITT
When to use Glycoprotein IIb/IIIa Receptor Antagonists in PCI?
- begin treatment with an IV GP IIb/IIIa receptor antagonist at the time of primary PCI in selected patients with STEMI who are receiving unfractionated heparin (UFH)
- Used in special cases: Thrombectomy, High-troponin, Complex lesions, Large thrombi, “Bail-out” Therapy
What are the Glycoprotein IIb/IIIa Receptor Antagonists for PCI?
- Abciximab
- Tirofiban
- Eptifibatide
Abciximab dose for PCI
0.25 mg/kg IV bolus, then 0.125 mcg/kg/min (maximum 10 mcg/min) x 12 hours
Tirofiban dose for PCI
- 25 mcg/kg IV bolus, then 0.15 mcg/kg/min x 18-24 hours
- In patients with CrCl ≤ 60 mL/min, reduce maintenance dose by 50% x 18 hours
- Contraindicated in patients on hemodialysis
Eptifibatide dose for PCI
- 180 mcg/kg IV bolus [max: 22.6 mg] (repeat 10 minutes later), then 2 mcg/kg/min (max: 15 mg/hour) x 18-24 hours
- n patients with CrCl < 50 mL/min, reduce maintenance dose by 50%
- Contraindicated in patients on hemodialysis
Therapy for fibrinolysis
- fibrinolytics
- antiplatelets
- anticoags
fibrinolytics
- Alteplase
- Reteplase
- Tenecteplase
What are the antiplatelet therapies for PCI?
- ASA
- P2Y12 Receptor Antagonist
ASA for fibrinolysis
325mg before fibrinolytics and then ASA 81mg once daily thereafter
P2Y12 Receptor Antagonist for fibrinolysis
Clopidogrel
Clopidogrel dose for fibrinolysis
- 300 mg loading dose for patients ≤75 years of age
- 75 mg dose for patients >75 years of age (don’t get a loading dose because it increases risk for bleeding)
GP IIb/IIIa Antagonists in fibrinolysis
not recommended -> Combination of IIb/IIIa antagonist and fibrinolysis associated with high rates of bleeding and ICH
Anticoagulation During Fibrinolysis
- UFH
- Enoxaparin
- If history of HITT -> Fondaparinux, Bivalirudin
- Patients with STEMI undergoing reperfusion with fibrinolytics therapy should receive anticoagulant therapy for a minimum of 48 hours, and preferably for the duration of hospitalization, up to 8 days or until revascularization if performed.
TIMI Flow Grade
- 0: No perfusion (no antegrade flow beyond occlusion)
- 1: Penetration without perfusion (contrast material passes beyond the area obstruction but fails to opacify the entire coronary bed distal to obstruction)
- 2: Partial reperfusion (delayed flow with complete filling of distal area)
- 3: Complete perfusion
TIMI Risk Score: factors
- for NSTE-ACS
- ≥65 y of age
- ≥3 risk factors for CAD
- Prior coronary stenosis ≥50%
- ST deviation on ECG
- ≥2 angina events in prior 24 hours
- Use of aspirin in prior 7 days
- Elevated cardiac biomarkers
TIMI Risk Score: percentages
- 0-1: 4.7%
- 2: 8.3%
- 3: 13.2%
- 4: 19.9%
- 5: 26.2%
- 6-7: 40.9%
Relative contraindications for fibrinolytic therapy
- History of chronic, severe, poorly controlled HTN
- Severe uncontrolled HTN on presentation: SBP > 180 mm Hg; DBP > 110 mm Hg
- Traumatic or prolonged (> 10 min) CPR
- Major surgery ( < 3 weeks)
- Recent internal bleeding (within 2-4 weeks)
- Prior ischemic stroke in > 3 months
- Dementia or any known intracranial pathology not covered in absolute contraindications
- Non-compressible vascular punctures
- Pregnancy
- Active peptic ulcer disease (PUD)
- Current use of anticoagulants (Higher INR = Higher risk)
Absolute contraindications for fibrinolytic therapy
- Active bleeding or bleeding diathesis (Excluding menses)
- Any prior intracranial hemorrhage (ICH)
- Ischemic stroke within 3 months (EXCEPT acute ischemic stroke within 4.5 hours)
- Structural cerebrovascular lesion
- Presence of malignant intracranial neoplasm
- Significant closed head or facial trauma within last 3 months
- Intracranial or intraspinal surgery within 2 months
- Severe uncontrolled HTN that is unresponsive to emergency therapy
- Aortic dissection
Monitoring of Perfusion After Fibrinolysis
- Monitor over 1 - 3 hours after initiation of fibrinolytic therapy
- Pattern of ST elevation
- Cardiac rhythm
- Clinical symptoms
for Fibrinolysis, what are we looking for in pattern of ST elevation?
reduction of at least 50% of the initial ST-segment elevation injury pattern on a follow-up ECG
for Fibrinolysis, what are we looking for in cardiac rhythm?
Maintenance or restoration of hemodynamic and/or electrical stability
for Fibrinolysis, what clinical symptoms are we looking for?
- want to monitor for Intracranial Hemorrhage (ICH)
- Usually occurs within first 24 hours of therapy
- Fibrinolytic, antiplatelet, and anticoagulant therapies should be discontinued until brain imaging scan shows no evidence of ICH
What are the presenting features of ICH?
- Acute change in level of consciousness
- Focal neurological deficits
- New/severe headache
- Nausea/vomiting
- Seizures
- Acute hypertension
- Drowsiness
- Coma
What is NSTE-ACS?
- Partial thrombus occlusion of coronary vasculature
- Plaque stability dictates whether patient will have ischemic or infarction
What falls under NSTE-ACS?
- Unstable Angina (UA)
- Non ST segment Elevation MI (NSTEMI)
Unstable Angina (UA)
- ST segment depression
- Absence of ST segment elevation
- Absence of Biomarkers
Non ST segment Elevation MI (NSTEMI)
- ST segment depression
- Absence of ST segment elevation
- Presence of Biomarkers
Ischemia-Guided Strategy
- Patients receive optimal anti-ischemic/anti-thrombotic medical therapy
- Not getting angiography
- Criteria: Low TIMI risk score (0-1), Low risk Tn (-) patients
- MONA-BAAS
- Maximize angina treatment
- In patients with NSTE-ACS (i.e., without ST elevation), IV fibrinolytic therapy should not be used!!!!!
Antiplatelet for Ischemia-Guided Strategy
- Clopidogrel: 300-600 mg LD
- Ticagrelor: 180 mg LD
Anticoag for Ischemia-Guided Strategy
- UFH
- Enoxaparin
- Dalteparin
- Fondaparinux
UFH dose for Ischemia-Guided Strategy
- Initial loading dose 60 IU/kg (max 4,000 IU) with initial infusion 12 IU/kg/hour (max 1,000 IU/hour)
- Use for 48 hours or until PCI is performed; aPTT of 1.5 to 2.0 times control
Enoxaparin dose for Ischemia-Guided Strategy
- IV bolus, followed by SQ injection for the duration of hospitalization, up to 8 days or until PCI performed
- 30-mg IV bolus then 1 mg/kg SQ every 12 hours
- Regardless of age, if CrCl < 30 mL/min -> 1 mg/kg SQ every 24 hours
Dalteparin dose for Ischemia-Guided Strategy
120 units/kg body weight SQ (maximum dose: 10,000 units) every 12 hours for up to 5-8 days
Fondaparinux dose for Ischemia-Guided Strategy
- Initial dose 2.5 mg IV, then 2.5 mg SQ daily starting the following day, for the durations of hospitalization, up to 8 days or until revascularization
- not recommended for monotherapy
- CI with CrCl < 30 mL/min
Early Invasive Strategy
MONA-BAAS
Antiplatelet for Early Invasive Strategy
- P2Y12 Receptor Antagonists
- GP IIb/IIIa Receptor Antagonist
P2Y12 Receptor Antagonists in Early Invasive Strategy
- Clopidogrel
- Ticagrelor
- Prasugrel
- Cangrelor
Clopidogrel dose for Early Invasive Strategy
300-600 mg LD
Ticagrelor dose for Early Invasive Strategy
180 mg LD
Prasugrel dose for Early Invasive Strategy
60 mg LD
Cangrelor dose for Early Invasive Strategy
30 mcg/kg IV bolus prior to PCI followed immediately by an infusion of 4 mcg/kg/minute continued for at least 2 hours or for the duration of the PCI
GP IIb/IIIa Receptor Antagonist for Early Invasive Strategy
- Use in pts that has NSTE-ACS and high-risk features and not adequately pretreated with clopidogrel or ticagrelor
- Can use if pre-treated adequately with clopidogrel plus ASA (DAPT)
- Eptifibatide
- Tirofiban
Eptifibatide dose for Early Invasive Strategy
- 180 mcg/kg IV bolus [max: 22.6 mg] (repeat 10 minutes later), then 2 mcg/kg/min (max: 15 mg/hour) x 18-24 hours
- Remember: In patients with CrCl < 50 mL/min, reduce maintenance dose by 50%
- Contraindicated in patients on hemodialysis
Tirofiban for Early Invasive Strategy
- 25 mcg/kg IV bolus, then 0.15 mcg/kg/min x 18-24 hours
- Remember: In patients with CrCl ≤ 60 mL/min, reduce maintenance dose by 50% x 18 hours
- Contraindicated in patients on hemodialysis
Anticoagulation for Early Invasive Strategy
- UFH
- Enoxaparin
- Dalteparin
- Fondaparinux
- Bivalirudin
- Argatroban
UFH dose for Early Invasive Strategy
- Initial loading dose 60 IU/kg (max 4,000 IU) with initial infusion 12 IU/kg/hour (max 1,000 IU/hour)
- Use for 48 hours or until PCI is performed
- aPTT of 1.5 to 2.0 times control
Enoxaparin dose for Early Invasive Strategy
- IV bolus, followed by SQ injection for the duration of hospitalization, up to 8 days or until PCI performed
- 30-mg IV bolus then 1 mg/kg SQ every 12 hours
- Regardless of age, if CrCl < 30 mL/min -> 1 mg/kg SQ every 24 hours
Dalteparin dose for Early Invasive Strategy
120 units/kg body weight SQ (maximum dose: 10,000 units) every 12 hours for up to 5-8 days
Fondaparinux dose for Early Invasive Strategy
- Initial dose 2.5 mg IV, then 2.5 mg SQ daily starting the following day, for the durations of hospitalization, up to 8 days or until revascularization
- not recommended for monotherapy
- CI with CrCl < 30 mL/min
Bivalirudin dose for Early Invasive Strategy
- Prior to angiography
- 0.75-mg/kg IV bolus, then 1.75–mg/kg/hour IV infusion
- Dose adjust for patients with renal dysfunction -> CrCl < 30 ml/min = 1 mg/kg/hour
Argatroban dose for Early Invasive Strategy
- direct thrombin inhibitor
- dose adjust with liver dysfunction
- good for pts with renal dysfunction
Invasive Strategy
- Diagnostic coronary angiography
- MONA-BAAS
What has to happen before invasive strategy is considered?
- Fail medical therapy
- Objective evidence of ischemia by non-invasive stress testing
- Hemodynamic or electrical instability
- Very high prognostic risk -> High TIMI/GRACE scores
What is the criteria for invasive strategy?
- Patient experiencing refractory/recurrent angina
- Electrical instability
- Hemodynamically unstable: Hypotensive, Change in mental status
- Troponin elevation
- TIMI score ≥ 2
antiplatelet for invasive strategy
- P2Y12 Receptor Antagonists
- GP IIb/IIIa Receptor Antagonist
P2Y12 Receptor Antagonists for invasive strategy
- Clopidogrel
- Ticagrelor
Clopidogrel dose for invasive strategy
300-600 mg LD
Ticagrelor dose for invasive strategy
180 mg LD
Anticoagulation for invasive strategy
- UFH
- Enoxaparin
- Dalteparin
- Fondaparinux
- Bivalirudin
UFH dose for invasive strategy
- Initial loading dose 60 IU/kg (max 4,000 IU) with initial infusion 12 IU/kg/hour (max 1,000 IU/hour)
- Use for 48 hours or until PCI is performed
- aPTT of 1.5 to 2.0 times control
Enoxaparin dose for invasive strategy
- IV bolus, followed by SQ injection for the duration of hospitalization, up to 8 days or until PCI performed
- 30-mg IV bolus then 1 mg/kg SQ every 12 hours
- Regardless of age, if CrCl < 30 mL/min -> 1 mg/kg SQ every 24 hours
Dalteparin dose for invasive strategy
120 units/kg body weight SQ (maximum dose: 10,000 units) every 12 hours for up to 5-8 days
Fondaparinux dose for invasive strategy
- Initial dose 2.5 mg IV, then 2.5 mg SQ daily starting the following day, for the durations of hospitalization, up to 8 days or until revascularization
- not recommended for monotherapy
- CI with CrCl < 30 mL/min
Bivalirudin dose for invasive strategy
- Prior to angiography
- 0.75-mg/kg IV bolus, then 1.75–mg/kg/hour IV infusion
- Dose adjust for patients with renal dysfunction -> CrCl < 30 ml/min = 1 mg/kg/hour
GP IIb/IIIa Receptor Antagonist for invasive strategy
- Eptifibatide
- Tirofiban
Eptifibatide dose for invasive strategy
- 180 mcg/kg IV bolus [max: 22.6 mg] (repeat 10 minutes later), then 2 mcg/kg/min (max: 15 mg/hour) x 18-24 hours
- Remember: In patients with CrCl < 50 mL/min, reduce maintenance dose by 50%
- Contraindicated in patients on hemodialysis
Tirofiban dose for invasive strategy
- 25 mcg/kg IV bolus, then 0.15 mcg/kg/min x 18-24 hours
- Remember: In patients with CrCl ≤ 60 mL/min, reduce maintenance dose by 50% x 18 hours
- Contraindicated in patients on hemodialysis
Secondary Prevention post-ACS
- DAPT Considerations
- High-intensity statin therapy
- Beta Blockers
- RAAS Blockade
DAPT Considerations for Secondary Prevention post-ACS
- ASA 81mg indefinitely
- P2Y12 Receptor antagonists: Clopidogrel, Prasugrel, Ticagrelor
Clopidogrel dose for Secondary Prevention post-ACS
75 mg PO once daily
Prasugrel dose for Secondary Prevention post-ACS
10 mg PO once daily
Ticagrelor dose for Secondary Prevention post-ACS
90 mg PO BID
How long should you use P2Y12 Receptor antagonists in Secondary Prevention post-ACS patients?
- if no stent: 1 year; bleeding concerns -> 14days - 1month
- BMS/DES stent: 1 year; bleeding concerns -> 6 months
- favorable DAPT score to extend, after 1 year of Ticagrelor 90mg BID, change to Ticagrelor 60mg BID
What is the favorable DAPT scores to continue P2Y12 Receptor antagonist therapy?
- Score ≥2 – favorable benefit/risk ratio for extending DAPT
- Score < 2 – Unfavorable benefit/risk ratio
- excludes patients who are on oral anticoagulation and/or patients with a high bleed risk
triple anti-thrombotic therapy
- Two antiplatelets + one anticoag
- Warfarin + ASA+ P2Y12 receptor antagonist
managing triple anti-thrombotic therapy
- Consider temporariliy holding the ASA therapy
- Add ASA back when P2Y12 receptor antagonist or warfarin can be discontinued
- Use clopidogrel as P2Y12 receptor antagonist
- Target INR goal of 2-2.5
Vorapaxar
- Indicated for Secondary Prevention of MI but increases risk of bleeding
- NOT to be used during AMI
- Place in therapy is currently unknown
ARA (Aldosterone Receptor Antagonists)
- Should be added to patients stabilized on ACE-I (ARB) / Beta Blocker who have EF ≤ 40% AND EITHER symptomatic HF OR DM
- Decreases risk of mortality
ACE-I (ARB)
- Will prevent cardiac remodeling
- administered within 24 hours and continue indefinitely
- mortality benefit
- ARB’s should be given to pts who cannot take ACEI
Beta Blockers in Secondary Prevention post-ACS
- Oral agent should be initiated in the first 24 hours
- Continued indefinitely
- Beta-blocker therapy should be started and continued for 3 years in all patients with normal LV function after ACS
- non-ISA
- treatment of SIHD, ALL beta blockers are equally efficacious
Relative contraindications of beta blockers
- prolong PR interval
- asthma
- COPD
Absolute contraindications of beta blockers
- 3rd degree or complete AV block
- cardiogenic shock
CSA (chronic stable angina)
- Stable coronary plaque
- Angina precipitated by exertion or emotional stress and relieved by rest
- Lack of biomarkers
- Transient ST-segment changes that develop during symptomatic episodes that resolves when the patient becomes asymptomatic
Pharmacotherapy to Prevent MI & Reduce Mortality
- ASA
- Clopidogrel is ADA is CI
- Beta blockers
- RAAS blockade
In patients that have LV systolic dysfunction (EF ≤ 40%) with heart failure or prior MI, which beta blockers should be used?
- carvedilol
- metoprolol succinate
- bisoprolol
Pharmacotherapy to Relieve Ischemic Symptoms
- Nitrates
- Beta Blockers
- Calcium Channel Blockers
- Ranolazine
Nitrates: effects on SIHD
- Improve exercise tolerance
- Improves time to angina onset
- Improves time to ST-segment depression
Short-Acting Nitrates
- for ALL patients
- Tablet: Max of 1.2 mg within 15 minutes; discard 6-12 months after opening
- Spray: 1-2 sprays onto or SL
Long-Acting Nitrates
- when beta blockers are contraindicated or cause unacceptable side effects or, in combination with beta blockers, for relief of symptoms when initial treatment with beta blockers is unsuccessful
- better in combination
- Patch: 0.1-0.6 mg/hr, Allow 10-12 hour patch-free interval
Nitrate Adverse effects
- Dyspepsia
- Headache
- Flushing
- Dizziness
- Hypotension
- Tachycardia
- Tachyphylaxis
Contraindications to Nitrates
- Hypotension: SBP <90 mm Hg or ≥30 mm Hg below baseline
- Tachycardia
- Bradycardia
- PDE5 inhibitors: Tadalafil / Cialis within 48 hours; Vardenafil / Levitra or Sildenafil / Viagra for 24 hours
Calcium Channel Blockers
- Non DHP helps with demand
- DHP helps with increase in supply
- Reduce angina symptoms
- Increase exercise duration
- Reduce SL nitroglycerin use
- NO MORTALITY BENEFIT
Ranolazine
- Inhibitor of late sodium ion channels -> prevent influx of Ca into the cells
- 500-1000 mg PO twice daily
- Substitute for beta blocker
- Can be added as background therapy
- Reduces angina frequency
- Improves exercise tolerance
Monitoring for signs/symptoms of bleeding
- Hypotension
- Thrombocytopenia
- aPTT
When should you give prasugrel?
Only give at time of PCI for patients with NSTEMI
What happens after clinician receives angiography results?
Will decide if pt gets medical therapy, PCI, or CABG
When should you discontinue P2Y12 Receptor Antagonist for procedures?
- Clopidogrel – 5 days prior
- Ticagrelor – 5 days prior
- Prasugrel – 7 days prior
Outpatient Check-list for ACS patients
- DAPT
- ACEI or ARB
- Beta blocker
- Statin
- Nitrate
- Select patients: ARA, Vorapaxar
Risk Factor Modification for cardiovascular diseases
- Lipid Management
- Blood Pressure Management
- Diabetes Mellitus Management
- Physical Activity
- Weight Management
- Smoking Cessation
- Alcohol Moderation
What is the BP target for pts with SIHD and HTN?
130/80 mmHg
Isosorbide Mononitrate, IR
- Monoket®
- 10-20 mg tablets give BID (7 hours apart)
Isosorbide Mononitrate, ER
- Imdur®
- 30, 60, 120 mg tablets given once daily in the AM
Isosorbide Dinitrate, ER
- Dilatrate SR®
- 40 mg once daily (If using BID: 18 hour dose-free interval )
Isosorbide Dinitrate, IR
- Isordil®
- 5-40 mg BID-TID (14 hour dose-free interval)
Adverse effects of Ranolazine
- Nausea / constipation
- Headache
- Dizziness
- Hypotension
- QTc Prolongation
Contraindications of Ranolazine
cirrhosis
Precautions of Ranolazine
- In patients with history of malignancy
- Intestinal tumorigenesis
Drug interactions of Ranolazine
- Major CYP3A4 Substrate; cannot take with inducers or inhibitors of this enzyme
- avoid grapefruit
- do not exceed 20mg simvastatin daily
- minor CYP2D6 substrate -> Dose adjust tricyclic antidepressants
- P-glycoprotein inhibitors
Why should you avoid use of short-acting nifedipine?
can cause reflex tachycardia
CCB drug interactions
- CYP3A4 Substrate; do not exceed 20mg simvastatin w/ amlodipine; do not exceed 10mg simvastatin w/ non DHP CCB
- beta blockers
CCB comorbid conditions
- HFrEF
- Cardiac conduction deficits: tachy or brady cardia
non DHP CCB adverse effects
- bradycardia
- constipation
DHP CCB adverse effects
- peripheral edema
- flushing
- headache