L7 pt.1 - acute angina, ACS, anti-coag, anti-platelet

what determines increased myocardial oxygen demand

• faster HR

• stronger contractions

• higher BP

• larger ventricular wall stress

what determines decreased myocardial oxygen demand

decreased oxygen supply

• CA narrowing

• coronary vasospasm

• coronary thrombosis

• severe anemia/hypoxemia

types of angina- stable angina

• predictable

• triggered by exertion

• releived by rest or nitro

• fixed plaque

types of angina- unstable angina

• unpredictable

• can occur at rest

• no reliably relieved

• plaque rupture/thrombus

types of angina- prinzmetal (vasospastic)

• episodic at rest

• coronary artery spasm

• relieved by nitrates/CCBs

• vaspspasm

stabel angina vs ACS: why rest does NOT fix MI

stabel angina

• fixed narrowing

• blood can stil get through

• rest decreased O2 demand

• sx improve

acute MI

• acute thrombotic occlusion

• blood flow suddenly stops

• rest cannot removes clot

• sx persist

nitroglycerin- primary effect

• venodialtion → decreased preload

• decreased wall stress

• decreased mypcardial oxygen demand

  • does NOT remove plaque, just hekps the heart cope with the narrowed artery

nitroglycerin- secondary effect

• coronary vasodilation

• improves O2 delivery

nitroglycerin- important contraindications

• sus RV infarction

• PDE 5 inhib

• hypotension

• severe AS

nitroglycerin- pt counseling

• sit or lie down before taking

• place UNDER tongue

  • do NOT shallow or chew

  • allow tablet to dissolve

• take 1 tablet

  • if pain persistat after 5min: call EMS

  • no more than 3 doses while waiting

• storage:

  • dark glass bottle’ protect from moisture (bc dissolve)

  • replace q6months after opening

long acting nitrates- agents

• isosorbide mononitrate

• isisorbide dinitrate

• nutroglycerin transdermal patch

long acting nitrates- site of action

• vascular smooth muscle

• venous capacitance vessels; some arterial dialtion

• result: coronary vasoDILATION

long acting nitrates-MOA

• organic nitrate converted to NO→ activate guanylate cyclase

• increase cGMP: smooth muscel relaxation

• venodilation >arterial dilation

• result: decreased preload

  • decreased LV wall stress

  • decreased myocardial oxygen demand

long acting nitrates-indications

chronic stable angina

• adjunct therapy when:

  • BB alone is inadequate

  • BB contraindicated

  • vasospastic angina

  • combo therapy for persistent sx

long acting nitrates- ADR

• HA

• hypotension

• orthostatic dizziness

• flushing

• reflex tachy

• syncope

long acting nitrates-monitor

• TOLERANCE develops rapidly→ requires daily nitrate free interval

• freq of episodes

• nitro use

• BP

• ortho sx

• headache tolerance

nitrate interactions- PDE5i

• profound hypotension

• clinical action: contraindicated

nitrate interactions- riociguat

• severe hypotension

• clinical action: contraindicated

nitrate interactions- alcohol

• additive vasodilation

• clinical action: use caution

nitrate interactions- other antiHTN

increased hypotension

clinical action: monior BP

nitrate interactions- other vasodilators

increased hypotension

clinical action: monitor

when to consider adding long acting nitro

• angina occurs frequently

• sx interfere with daily activities

• pt needs nitro repeatedly

• BB along insuff

• BB cannot be used

nitro vs long acting nitrates

nitroglycerin

• rescue med

• works in 1-5min

• takes only chen chest pain occurs

• stops angina attack

• short duration

• carry with the pt at all time

long acting nitrates

• prevention med

• works over hours

• tajen every day

• reduced how often attacks occur

• long duration

• not useful for immediate relief

beta blockres- why do they help

• decreased myocardial O2 demand

• decreased HR

• decreased myocardial contractility

• decreased BP

• increased idastolic fill time, improving coronary perfusion

beta blockers- role in therapy

• generally first lien in antianginal therapy, esp with:

  • prior MI

  • HFrEF

  • tachy

• reduce angina freq adn improve exercise tolerance

• do NOT relieve acute chest pain

beta blockers- clinical pearls

• use cardio selective BB (metoprolol)

• do NOT stop abruptly→ rebound tachy, HTN, and worsening ischemia

• avoid/use caution in:

  • severe brady

  • high grade AV block

  • cardiogenic shock

  • acute decomp HF

• reduce O2 demand by making heart beat slower adn less forcefully

CCB- why do they help

• decrease myocardial oxygen demand

• decreased afterload (DHP CCB)

• decreased BP

• decreased cardiac workload

• improve myocardial oxygen supply

• relieve coronary vasospasm

CCB- role in therapy

• first line antianginal alternatives to BB when contraindicated or not tolerated

• add on therapy for persistent angina despite initial therapy

• first line treatment for vasospastic angina

CCB- clinical pearls

• DHP CCBs (amlodapine, nifedipine): greater vasodilation; amlodapine may be used in HFrEF if needed fro angina/HTN

• nonDHP CCBs (diltiazem, verapamil): lower HR adn contractility

  • avoid in HFrEF

  • use caution when combined with BB due to brady/AV block

high intensity statins- why do they help

• stabilize atherosclerotic plaque

  • lower LDL

  • slow progression of atherosclerosis

  • reduce risk of MI, stroke, adn cardiovascular death

high intensity statins- roel in therapy

• recommended fro all pts with ACS

• recommended for pts with chronic coronary disease unless contraindicated or not tolerated

high intensity statins dosages

• atorvastatin 40-80mg

• rousuvastatin 20-40mg

ranolazine

makes ischemic heart muscle more energy efficient

ranolazine- site of action

• cardiac myocytes (ischemic myocardium)

• acts on late Na channels in ventricular cardiac muscel cells

• primarily affects ischemic rather than healthy myocardium

ranolazine- MOA

• during mycardial ischemia, there is an increase in late Na influx into cardio myocytes

• increase intracellular Na leads to increased intracellular Ca

• excess Ca leads to:

  • decreased ventricular relaxation

  • increased LV wall tension

  • increased myocardial O2 consumption

• ranolazine blocks the late Na current→ decreased intracellular Na and Ca

ranolazine- result

• improved vent relaxation

• reduced wall stress

• imporved myocardial efficiency

• fewer angina sx

ranolazine- indications

• chronic stable angina

• persistenet sx despite first lien therapy

• cannot tolerate BB

• can be added to:

  • BB

  • CCB

  • long acting nitrates

ranolazine pearl

• does NOT sig lower HR or BP→ useful when those limit other therapies

ranolazine ADR

• dizziness- CNS effects

• HA- mild vasodilatory effects/central effects

• constipation- GI smooth muscle lesions

• nausea- GI intolerance

• QT prolongation

ranolazine- monitoring

• improvemenr in angina sx

• change in freq of nitro use

• ECG (OT inerval)

• renal function (esp severe impairment)

• hepatic impairment (avoid sig liver dz)

ranolazine DDI- strong CYP3A4 i

• increase ronolazine effects

• contraindicated

ranolazine DDI- moderate CYP3A4i

• increase ranolazine levels

• limit ranolazine dose

ranolazine DDI- CYP3A4 inducers (rifampin)

• decrease ranolazine effectiveness

• avoid combo

ranolazine DDI- QT prolongin gdrugs

• additive QT prolongation

• use caution

ranolazine DDI- digoxin

• increased digoxin concentration

• monitor dig

tx of stable angina

• lifestyle/RF modification

• PRN nitro

• sx?

  • add BB, CCB, or logn acting nitro

• still sx?

• persistent sx?

meds that reduce CV risk when indicated- stable angina

• antiplatelet therapy

• high intensity statin

• ACEi-ARB fro sppropriate comorbidities

• SGLT2i/GLP-1 RA in selecte dpts

• smoking cessaiton/cardiac rehab

meds that imporves angina sx- stable angins

• SL.long actign nitrates

• CCBs

• ranolazine

• BB

when not to use- nitrates

• recent sildenafil/tadalafil

  • severe hypotension

  • better option: treat ACS, avoid nitrates until safe interval

• severe hypotension

  • further bP reduction

  • better option: individualize therapy

when not to use- nonselective BB

• vasospastic angina

• may worsen coronary spasm

• better option: CCB

when not to use- BB, non DHP CCBs

• bradycardia or AV block

• further slows HR/AV conduction

• better option: ranolazine or long acting nitrate

when not to use- verapamil, diltiazem

• HFrEF

• negative intropy

• better option: evidence based BB

when not to use- ranolazine

• QT prolongation

• may worsen QT prolongation

• better option: alternative antianginal

when to get coronary angio

• persistent angina despite optimal medical therapy (OMT)

• sx sig limit quality of life

• high risk findings on stress testing

• sus high risk coronary anatomy

stable angina vs acute coronary syndrome

stable angina

• fixed plaque

• predictable

• demands exceeds supply

• exercise induced

• relieved with rest

• antianginals

ACS

• plaque rupture

• sudden

• supply abruptly stops

• often occurs at rest

• persistent

• antiplatelets + anticoag + reperfusion

optimal medical therapy- stable angina

• guidance directed risk reduction (aspirin, statin ± ACEi/ARB)

• approp antianginal medications

• sx remain despite med optimization

roles of medical interventions- angina

• reduces myocardial oxygen demand

• prevents plaque progression

• prevents future CV events

• long term disease mgmt

roles of surgical interventions- angina

• improves coronary blood flow

• treats sig obstructive lesions

• relieves ischemia caused by severe stenosis

• mechanical revascularization

ACS spectrum- unstable angina

• artery: partial blockage

• heart muscle: no permanent injury (yet)

• initial med priorities: aspirin, P2Y12i, anticoag, anti-ischemic therapy (notro, BB)

• ultimate goal: prevent progression to MI

ACS spectrum- NSTEMI

• artery: partial block

• heart muscle: myocardial injury has begun

• iniital med priorities: aspirin, P2Y12i, anticoag, anti ischemic therapy, high intensity statin

• ultimate goal: prvent initial myocardial damage while preparing for early angio ± PCI

ACS spectrum- STEMI

• artery: complete blockage

• eeart muscle: active myocardial infarction

• initial med priorities: aspirin, P2Y12i, anticoag, immediate reperfusion (PCI preferred; fibryn if PCI unavailable), high intesnsity statin

• restore coronary blood flow as quickly as possible

type 1 MI

• plaque rupture

• TEMI/NSTEMI

• treat coronary thrombus

• full ACS pharm

ACS pharm strategy

• platelets

  • aspirin

  • P2Y12

• coag

  • UFH

  • LMWH

  • DOACs

  • warfarin

• existing clot

  • fibrinolytics

  • PCI

• long term prevention

  • statins

  • BB

  • ACEi

aspirin-SOA

• platelets, cyclooxygenase-1 (COX-1)

aspirin- MOA

• irreversibly inhibits COX1

• decease thromboxane A2 (TXA2) production

• decrease platelet acticvation adn aggregation

aspirin- indications

• ACS

• secondary prevention of MI

• ischemic stroke

• PAD

aspirin- ADRs adn monitoring

• ADRs

  • bleeding

  • GI irritaiton

  • PUD

  • tinnitus

• monitorig

  • signs of bleeding

  • GI sx

antiplatelet- P2Y12 inhibitors

• clopidogrel

• prasugrel

• ticagrelor

antiplatelet- P2Y12 inhibitors- MOA

• reversibly ro irreversibly inhibit P2Y12 (ADP) receptor

• prevent ADP mediated platelt activation

• prevent GP IIb/IIIa receptor activation

• reduce platelet aggregation

• other words:

  • after plaque rupture, activated platelets release ADP→ recruitment signal to tell platelets to come help build clot

  • P2Y12i block platelet ability to recieve that ADP signal→ decreased platelet activation, decreased platelet recruitment, decreased platelet aggregation

antiplatelet- P2Y12 inhibitors- common uses

• ACS

• PCI

• DAPT

antiplatelet- P2Y12 inhibitors- sometimes uses

• secondary prevention after MI

• aspirin intolerance

antiplatelet- P2Y12 inhibitors- common ADE

• bleeding

• bruising

• epitaxis

antiplatelet- P2Y12 inhibitors- drug specific ADRs

• dyspnea (ticagrelor)

• rare TTp (clopidogrel)

• bradyarrythmias (ticagrelor)

antiplatelet- P2Y12 inhibitors- monitoring

• signs of bleeding

• CBC/hbg

• adherence

• dyspnea

antiplatelet- P2Y12 inhibitors DDI- NSAIDs

• increase bleeding risk

antiplatelet- P2Y12 inhibitors DDI- antocoags

• increased bleeding risk

antiplatelet- P2Y12 inhibitors DDI- SSRis/SNRIs

• increased bleeding risk

antiplatelet- P2Y12 inhibitors DDI- strong CYP3A i

• increased ticagrelor levels

antiplatelet- P2Y12 inhibitors DDI- CYP2C19i (omeprozole)

• decreased clopidogrel activation

  • some ppl rapid metabolizers, so be careful

which P2Y12i- clopidogrel

• activation: prodrug

• onset: slower

• pearl: most commonly used; affected by CYP2C19 genetics/drug interactions

which P2Y12i-prasugrel

• activation: prodrug

• onset: faster

• pearls: more potent; avoid in prior stroke/TIA

which P2Y12i- ticagrelor

• activation: active drug

• onset: fast

• pearls: reversible inhibitor; may cause dyspnea; BID

which P2Y12i- cangrelor

• activation: IV (active)

• onset: immediate

• pearls: cath lab only; bridge during PCI