Stable Angina + ACS

what is stable angina?

• chronic coronary disease

• predictable chest pain

• relieved within minutes by rest or short-acting NTG

what is unstable angina?

• acute coronary syndrome (ACS)

• not relieved with NTG or rest

what is coronary artery disease (CAD)?

• stable angina - myocardial oxygen demand decreased due to atherosclerosis (plaque build up)

• causes narrowing of the arteries and reduced blood flow to the heart

what is vasoplastic angina?

• chest pain caused by coronary artery vasospasm

• can occur at REST and be caused by illicit drug use (cocaine)

how to diagnose likelihood of CAD and stable angina?

• cardiac stress test

what does the cardiac stress test consist of? (2)

increases oxygen demand with either

• exercise

• IV medications

  • adenosine, dipyridamole, dobutamine, regadenoson (Lexiscan)

non-pharm for stable angina (3)

• heart healthy diet

• BMI of 18.5-24.9

• waist circumference of <35 in females, and <40 in males

• aerobic exercise (≥150 min/week)

• quit smoking

• limit alcohol intake

Can chronic NSAID use be used in stable angina?

NO

T/F: Stable angina is considered a type of ASCVD

TRUE

Antianginal MOA in stable angina (2)

• decreases myocardial oxygen demand

• increases myocardial oxygen supply

antianginal drugs (3)

• BBs

• CCBs

• long-acting nitrates

what should be added if the patient remains symptomatic with initial monotherapy for stable angina?

• add a second antianginal drug from diff therapeutic class

when can ranolazine be added for stable angina?

• once the therapies have been used prior

when is short-acting NTG recommended?

• recommended for immediate relief for ALL patients

• SL tablet or translingual (TL) spray

what antiplatelet is recommended in stable angina?

• ASA

• clopidogrel only for allergy or contraindication to ASA

ASA MOA

• irreversibly inhibits COX-1 and COX-2

• decreased PG and TXA2 production

• TXA2 is a potent vasoconstrictor and inducer of platelet aggregation

clopidogrel MOA

• prodrug that irreversibly inhibits P2Y12 platelet activation and aggregation

treatment approach for stable angina (ABCDE)

• A: antiplatelet and antianginal drugs

• B: BP

• C: cholesterol (statins and cigs cessation)

• D: Diet and diabetes

• E: exercise and education

what two meds should be started in ACS? (2)

• ACEi/ARB

• high-intensity statin

Aspirin Brand Names (3)

• Bayer

• Bufferin

  • Ecotrin

what form of ASA is RX only?

• ER capsule (Durlaza)

ASA dosing in stable angina

75-100mg daily

safety/SEs/monitoring of ASA

• contraindications

  • salicylate allergy

  • children and teenagers with viral infection d/t risk of Reye’s syndrome

• warnings

  • bleeding

  • tinnitus (salicylate overdose)

• SEs

  • dyspepsia

  • heartburn

  • bleeding

• Notes

  • used indefinitely in stable angina

  • non-enteric coated, chewable preferred in ACS

    • if only EC ASA available, chew 325mg

  • ER products should NOT be used if rapid onset

  • PPIs may be used to protect the GI tract from chronic ASA use

    • consider risks of PPI use (dec bone density, inc infection risk)

clopidogrel recommended dose in stable angina

75mg daily

what metabolite is clopidogrel?

CYP2C19

when should clopidogrel be stopped prior to an elective surgery?

5 days prior

what 2 drugs should clopidogrel not be used with?

• omeprazole

  • esomeprazole

what bleeding disorder can occur with clopidogrel?

TTP

• thrombotic thrombocytopenic purpura

how do BBs help in stable angina?

• dec HR, contractility, and left ventricular wall tension

when should BBs not be used in stable angina?

vasoplastic anginax

how do CCBs help in stable angina?

• non-DHPs: dec HR and contractility

  • DHP: dec SVR (afterload)

which CCB should be avoided in stable angina?

• short-acting nifedipine IR

what CCBs are preferred when used with a beta blocker?

• DHPs (due to risk of excessive bradycardia when non-DHPs are used)

what antianginal is preferred for vasospastic angina?

• CCBs

how do nitrates help in stable angina?

• dec preload

  • free radical NO produces vasodilation of veins more than arteries

clinical notes of ranolazine

• contraindication: CYP3A4 inducers/inhibitors (protease inhibitors/cobicistat)

• warnings: QT prolongation

• Notes: not for acute treatment of chest pain

  • has little effect on HR and BP

short-acting nitrates (2)

• NTG SL tablet (Nitrostat)

  • NTG TL spray (Nitromist, Nitrolingual)

long-acting nitrates (2)

NTG ointment 2% Nitro-Bid

isosorbide mononitrate

safety/SEs/monitoring of nitrates

• contraindications

  • do not use with PDE-5 inhibitors or soluble guanylate cyclase stimulators

• warnings

  • hypotension

  • tachyphylaxis

  • tolerance/dec effectiveness

• SEs

  • headaches

  • flushing

  • syncope

• Notes

  • Short-acting

    • PRN for immediate relief of chest pain

    • store NTG SL tablets in original container amber glass

  • long-acting

    • requires 10-12 hr nitrate-free interval to dec tolerance

    • patch: wear on for 12-14 hrs

    • ointment: dosed BID; 6 hrs apart

    • isosorbide mononitrate: IR dosed BID; 7 hrs apart (8am and 3pm)

  • isosorbide dinitrate/hydralazine is the preferred combo in HFrEF

short-acting nitrates counseling

• call 911 immediately if chest pain persists after first dose

• take 2 additional doses 5 minutes apart while waiting

  • do not take more than 3 doses within 15 min

NTG SL tablets

• place the tablet under the tongue and let it dissolve

• slight burning or tingling is NOT a sign of how well the med is working

  • keep tightly in amber glass bottle at room temp

NTG TL spray counseling

• do NOT shake

• spray onto or under the tongue

  • do not inhale the spray

what is the preferred site for NTG patch?

chest

NTG ointment counseling

• measure the dose on dose-measuring applicator

• tape the applicator into place of the skin

• can stain clothing!!

what is ACS?

• plaque build up (atherosclerosis) in the coronary arteries

• plaque can rupture, clot formation, and sudden, reduced blood flow (ischemia)

• causes imbalance between myocardial oxygen supply and demand

what are the classic symptoms of ACS?

• chest pain*** (pressure or squeezing)

  • lasts ≥10 minutes, severe dyspnea, diaphoresis

where does chest pain radiate to in ACS?

• arms

• back

• neck

• jaw

  • epigastric region

risks factors for plaque build up (10)

1. age: males >45 yrs; females > 55 yrs (early hysterectomy)

2. fam hx (first degree)

3. smoking

4. HTN

5. known CAD

6. dyslipidemia

7. diabetes

8. chronic stable angina

9. lack of exercise

10. excessive alcohol

what domains does ACS consists of ? (2)

1. NSTE-ACE

2. STEMI

what does NSTE-ACS consist of (2)

1. NSTEMI

2. unstable angina

what should be done within 10 min at the site of first medical contact?

12-lead

if patients have MI, where should they be transported?

hospital with PCI capability

which cardiac enzymes are the most specific/sensitive for ACS?

troponins I and T (TnI and TnT)

how can NSTE-ACS be treated (2)?

1. PCI (early invasive strategy)

2. medications alone

when should PCI be performed in STEMI? (2)

• within 90 minutes of hospital arrival (optimal door-to-balloon time)

• within 120 minutes of first medical contact

if PCI is not possible for STEMI, what is recommended?

fibrinolytic therapy

• within 30 min of hospital arrival (door-to-needle time)

if PCI not availble within 120 min of first medical contact

what combination of drugs should be given after PCI/fibrinolytic therapy (3)?

1. antianginal

2. antiplatelet

3. anticoagulant

antianginals MOA

• decrease myocardial oxygen demand or increase supply to relieve ischemia

antiplatelets MOA

• inhibit platelet aggregation to prevent clot formation/growth

anticoagulants MOA

inhibit clotting factors to prevent clot formation/growth

Drug Treatments for ACS

• Morphine

• Oxygen

• Nitrates

• Aspirin

• GIIb/IIIa antags

• Anticoagulants

• P2Y12 inhibitos

• Beta blockers

• ACE inhibitors

why should immediate-release nifedipine NOT be used in ACS?

increased mortality

how do nitrates help in ACS?

• dilate coronary arteries

• improve blood flow

• decreased preload and afterload

• reduces chest pain

what dose of nitates should be given in ACS?

sublingual NTG 0.4mg every 5 minutes for 3 doses

can IV NTG be given?

• YES if sx present

  • avoid IV NTG if SBP <90mmhg

what dose of ASA should be given in ACS?

non-enteric coated, chewable aspirin 165-325mg to ALL patients immediately

• do NOT use extended-release ASA

what maintenance dose of ASA should be continued indefinitely after ACS?

ASA 75-100mg daily

GIIb/IIIa antags (2)

• eptifibatide

• tirofiban

anticoagulants used in ACS (3)

• LMWHs (enoxaparin, dalteparin)

• UFH and bivalirudin (preferred for STEMI)

P2Y12 inhibitors (3)

• clopidogrel (Plavix)

• ticagrelor (Brilinta)

• prasugrel (Effient)

what clinical benefit do BBs have in ACS?

• increased long-term survival

what 2 classes should be started within first 24 hrs of ACS?

1. BBs

2. ACEi (indefinitely)

what type of BB should be initiated in ACS?

• oral, low-dose BB

• Beta-1 selective w/o ISA is preferred

ASA MOA

irreversibly binds to COX-1 and COX 2 which decreases production of TXA2 (inducer of platelet aggregation)

P2Y12i MOA

bind to platelet adenosine diphosphate (ADP) P2Y12 receptors

• prevents ADP-mediated activation of GPiib/IIIa receptor complex

GPIIb/IIIa receptor antags MOA

• block platelet IIb/IIIa receptor, binding site for fibrinogen, vWF

protease-activated receptor-1 antags MOA

binds to PAR-1 receptor

• prevents thrombin- and thrombin receptor agonist peptide-induced platelet aggregation

• (vorapaxar)

which P2Y12 inhibitors are thenopyridines (2)

• clopidogrel

• prasugrel

• prodrugs that irreversibly bind to receptor

what type of dose is needed for P2Y12 inhibitors?

higher one-time loading dose

• either prior to PCI or at time of dx if PCI is not being performed followed by maintenance dose

which P2Y12 inhibitor is contraindicated with hx of stroke/TIA?

prasugrel (Effient)

how should prasugrel be dispensed?

in the original container

how many days should prasugrel be stopped prior to an elective surgery?

7 days

what is the maintenance dose of ticagrelor (Brilinta)?

90mg PO BID for 1 year; then 60mg BID

which P2Y12 inhibitors can lead to TTP?

clopidogrel

prasugrel

ticagrelor

what is the max maintenance dose of ASA when on ticagrelor?

100mg daily max

• higher doses can reduce the effectiveness of ticagrelor

how many days prior should ticagrelor be stopped before any surgery?

5 days prior

which P2Y12 inhibitor can cause dyspnea?

ticagrelor

which P2Y12 inhibitor is available IV?

cangrelor (Kengreal)

• transition to oral P2Y12 inhibitor after PCI

• only indicated adjunct to PCI in pts who are P2Y12 naive and not receiving GPIIb/IIIa inhibitor

if a patient on a P2Y12 inhibitor experiences bleeding, how should it be managed?

• should be managed without discontinuing the P2Y12 inhibitor

• stopping within the first few months after ACS inc risk of subsequent CV events

which meds in the risk of bleeding? (4)

• NSAIDs

• warfarin

• SSRIs

• SNRIs

what is given with GPIIb/IIIa antags if used in PCI?

heparin

what statins should be avoided with ticagrelor (2)?

• simvastatin and lovastatin >40mg/d

2 major side effects of GPIIb/IIIa inhibitors?

• bleeding

• thrombocytopenia

fibrinolytics MOA

fibrinolysis (clot breakdown)

• binds to fibrin and coverts plasminogen to plasmin

what are 2 fibrinolytics?

• alteplase (Activase) (tPA)

  • recombinant tissue plasminogen activator

• tenecteplase (TNKase)

  • single IV bolus dose

contraindications of fibrinolytics for ACS

• active internal bleeding

• hx of recent stroke

• severe uncontrolled HTN

• alteplase contraindications and dosing differ when used for ischemic stroke

for secondary prevention, which meds are continued indefinitely? (5)

• ASA

• NTG

• ACEi

• aldosterone antag

• statin

which P2Y12s should be used in DAPT for medical management?

• ticagrelor

• clopidogrel