Cardio IE2 TSU

ASCVD

• definition

• examples

• definition

  • diseases due to atherosclerotic plaques

• examples

  • acute coronary syndrome (ACS): MI, angina

  • coronary revascularization

  • stroke

  • PAD

secondary prevention

• pts with history of MI, stroke, PAD, revascularization

• treatment

  • high-intensity statin w/ target LDL < 70 mg/dL and non-HDL < 100 mg/dL

  • consider LDL < 55 mg/dL and non-HDL < 85 mg/dL in high risk pts

primary prevention — severe hypercholesterolemia

• LDL >/= 190 mg/dL

• treatment

  • high intensity statin

  • target LDL-C < 70 mg/dL and non-HDL-C < 100 mg/dL if add CV risk factors

  • target LDL-C < 55 mg/dL and non-HDL-C < 85 mg/dL if ASCVD present

primary prevention — diabetes

• age 40 - 75 w/ diabetes and LDL >/= 70 mg/dL

• treatment

  • moderate or high intensity statin

  • target LDL < 100 mg/dL and non-HDL < 130 mg/dL

  • target LDL < 70 mg/dL if multiple ASCVD risk factors or 10 yr risk factor > 10%

primary prevention — ASCVD risk

• age 40 - 75 w/ diabetes and LDL >/= 70 mg/dL and 10 yr risk score >/= 5%

• treatment

  • moderate or high intensity statin

  • target LDL < 100 mg/dL

  • target LDL < 70 mg/dL if multiple ASCVD risk factors or 10 yr risk factor > 10%

what to add if LDL still above goal on max tolerated dose of statin?

• ezetimibe

• PCSK9 inhibitors (mAb)

• bempedoic acid

• inclisiran (in place of PCSK9 inhibitors)

calculate PREVENT score if patient is

• 40 - 75 years old

• no ASCVD

• no diabetes

• LDL 70 - 189 mg/dL

PREVENT score: recommendation

• low risk (< 3%)

• borderline (3 - 5%)

• intermediate (5 - 10%)

• high (> 10%)

• low risk (< 3%)

  • lifestyle modification

• borderline (3 - 5%)

  • lifestyle modification, consider moderate statin

• intermediate (5 - 10%)

  • moderate-high statin

• high (> 10%)

  • high intensity statin

PREVENT score includes

• age

• gender

• BP

• cholesterol

• eGFR

• BMI

• DM

• smoking status

ASCVD risk enhancers

• Coronary artery calcium (CAC)

  • measures amt of calcium deposited in coronary artery

  • surrogate marker for severity of atherosclerosis

• Lp(a)

  • inherited and not affected by lifestyle modifications

• ApoB

  • tested on those who are not on therapy

high intensity statins

• atorvastatin (Lipitor) 40 - 80 mg

• rosuvastatin (Crestor) 20 - 40 mg

moderate intensity

• atorvastatin (Lipitor) 10 - 20 mg

• rosuvastatin (Crestor) 5 - 10 mg

• simvastatin (Zocor) 20 - 40 mg

• pravastatin (Pravachol) 40 - 80 mg

statins

• HMG-CoA reductase inhibitors (block cholesterol synthesis)

• DOC for primary and secondary prevention

statins: benefits vs risks

• benefits

  • decrease stroke

  • decrease coronary events

• risks

  • cognitive dysfunction

  • risk of haemorrhagic stroke

  • liver disease

  • new onset DM

  • SAMS

SAMS

• myopathy

  • muscle pains

  • bilateral

  • within weeks of statin

  • reversible upon dicontination

• rhabdo

  • increased Scr

  • brown urine

  • muscle pain

  • rare

  • discontinue statin

risk factors of SAMS

• 65+

• female

• low BMI

• obesity

• hypothyroidism

• drug interactions

• chronic kidney/liver disease

• alcohol

• vigorous exercise

• genetics

management of SAMS

• discontinue statin

• assess whether sx improved

• rechallenge statin at same dose, reduce dose, change statin (hydrophilic), alternate dosing, change to other

other statin side effects

• memory loss and confusion

• hepatotoxicity

• increased incidence of type 2 diabetes

statin CI

• hypersensitivity

• active liver disease

• pregnancy/lactation

  • generally avoid

  • stope 1 - 2 months before pregnancy

statins: lipophilic vs hydrophilic

• lipophilic

  • simvastatin (t ½ 14 h)

  • lovastatin

  • atorvastatin

• hydrophilic

  • pravastatin (no metabolism)

  • rosuvastatin (t ½ 19 h)

common DDIs of statins

• grapefruit juice

• antifungals

• cyclosporine

• gemfibrozil

• amiodarone

• bempedioic acid

• colchicine (monitor

which statins are susbtrates of P-gp

• lovastatin

• simvastatin

• atorvastatin

can interact w/ P-gp inthibitors and CYP3A4 inhibitiors

• -zoles, HIV afgents, -mycins, etc

statin of choice for CKD

atorvastatin and fluvastatin (no dose adjustments)

coEnzyme Q10 (CoQ10)

• naturally occuring fat soluble ubiquinolone

• transported in LDL, HDL, VLDL

• statins may decrease COQ10 levels

• supplementation could help prevent myopathy

statin patient education

• work best at night

• atorvastatin, rosuvastatin, pitavastatin → taken any time (long t ½ )

• mild muscle pains

• rhabdo rare

• liver failure/hepatotoxicity rare

monitor statin efficacy

• fasting lipid panel 4 - 12 weeks (1 - 3 months) after intiation or dose change

• monitor every 6 - 12 months after

• if insuffient response:

  • lifestyle changes

  • exclude secondary causes

  • increase to max tolerated

  • consider non-statin therapy

monitoring statin safety

• prior to starting

  • liver functions, A1C, CK

• do not start if LFTs > 3x upper limit of normal

• monitor if symptomatic

non-statin therapies

• lower level of rec

• consider add on to statin in high ASCVD risk pts on max tolerated statin

• best evidence

  • ezetimibe and PCSK9 mAb (expensive)

• alternative for pts who are statin intolerant

ezetimibe (Zetia)

• MOA

• combo product

• side effects

• MOA

  • lower cholesterol by inhibiting absorption of bilary and dietary cholesterol in small intestine

• combo product

  • Vytorin (+ simvastin)

• side effects

  • GI complaints, possible rhabdo, myopathy, increased LFTs in combo w/ statins

• can take w/ or w/o food

PCSK9 mAb

• drugs

• MOA

• potency

• administration

• effects

• approval

• cost

• drugs

  • Alirocumab (Praluent)

  • Evolocumab (Repatha)

• MOA

  • bind to PCSK9, prevent binding to LDL receptor

• potency

  • very potent LDL lowering meds

• administration

  • injections (monthly or bimonthly)

• effects

  • reduce LDL and CV events

• approval

  • familial hypercholesterolemia or pts secondary prevention

• cost

  • expensive

bempedoic acid

• MOA

• approval

• ADE

• MOA

  • ACL inhibitor; acts upstream of HMG-CoA reducase in cholesterol synthesis pathway

• approval

  • familial hypercholesterolemia

  • primary or secondart prevention

• ADE

  • increased UA levels

  • risk of tendon rupture

inclisiran

• MOA

• administration

• indications

• MOA

  • synthetic double stranded small interfering RNA directed at liver where PSCK9 proteins made

• administration

  • SQ: day 1, day 90, every 6 months

• indications

  • familial hypercholesterolemia

  • high risk ASCVD who have not met LDL-C goals on other therapy

BAS

• drugs

• MOA

• effects

• SEs

• dosing/administration

• education

• drugs

  • Colesevelam (Welchol)

  • Colestipol (Colestid)

  • Cholestyramine (Questran)

• MOA

  • bind to bile salits in intestines → increase in LDL removal

• effects

  • also lovers glucose levels

• SEs

  • Gi complaints

  • decreased concurrent drug absoprtion

  • constipation

  • increased TG: avoid if TG > 300 mg/dL

• dosing/administration

  • suspension

• education

  • GI: increase fluid intake, bulk diet, stool softener

  • DI: administer other meds 1 hr before or 4 hrs after BAS

  • take w/ food

Hypertriglyceridemia

elevated TG > 150 mg/dL

treatment of hyperTG: nonpharm

• dietary

  • reduce/eliminate alcohol

  • reduce saturated fats/sugar/refined carbs

  • weight loss

  • phyiscal activity

higfh levels (> 500 mgdL) increase risk for

pancreatitis

hyperTG treatment

• statins

  • 1st line to reduce ASCVD risk if TG < 1000 mg/dL (lower by 20 - 40%)

• icosapent ethyl

  • added if pt has ASCVD or diabetes, on max tolerated statin, TG 150 - 500 mg/dL

• fibrates or omega 3 fatty acids

  • for severe hyperTG

omega 3

• reduces inflammation, VLDL

• sources

  • whole grains, fish

omega 6

• increases inflammation

• sources

  • meat, veggie oil

3 major types of omega 3

• ALA

• EPA

• DHA

side effects of omega-3 fatty acids

• belching fishy taste and reflex

• possible increased bleeding at higher dose

• caution w/ anticoagulants

fibrates

• Drugs

• MOA

• ADE

• caution

• DDIs

• use w/ statins

• Drugs

  • Gemfibrozil (Lopid)

  • Fenofibrate (Tricor, Trillipex)

• MOA

  • decrease VLDL via increased clearance and decreased synthesis

• ADE

  • GI upset

  • hepatotoxicity

  • myopathy

• caution

  • mild to moderate renal impairment

  • CI in CrCl < 30

• DDIs

  • gemfibrozil inhibits CYP 1A2, 2C9, 2C19

• use w/ statins

  • gemfibrozil: risk > benefit, not recommended

  • fenofribrate: okay

Niacin (Nicotinic acid)

• MOA

• place in therapy

• SE

• monitor

• MOA

  • decrease hepatic synthesis of VLDL and LDL

  • increase TG rate of removal

• place in therapy

  • last line for severe hyperTG due to SEs

• SE

  • flushing, itching

  • hepatotoxicity

  • hyperglycemia

  • hyperuricemia

• monitor

  • LFTs

  • A1C

  • uric acid before initation and every 6 months

special populations: children/adolescents

• drug therapy not recommneded until age 8

• lifestyle management = cornerstone of therapy

• assess for familial hypercholesterolemia

PAD

• most common form of peripheral vascular disease

• part of systemic disease of atherschlerosis

• restrict blood circulation

• considered ASCVD

PAD risk factors

• diabetes

• age

• smoking HTN

• hyperlipidemia

clinical presentation

• early stages

• later stages

• more

• early stages

  • asymptomatic

• later stages

  • pain and discomfort

• intermittent claudication

• pain at rest

intermittent claudication

• cramp tightening sensation in calf

• unilateral

  • bilateral over time

• pain resolves within mins of stopping and standing

ischemic rest/nocturnal pain

• claudiation to rest pain = severe disease

• involves foot

• occurs at night

• progresses to limb ischemia

diagnosis

• history

• physical exam

• clinical presentation

• ABI

• history

  • symptom onset

  • distance before onset of pain

  • pain releived by standing

• physical exam

  • arterial insufficiency

  • check femoral, popliteal, dorsalis pedis pulses

• clinical presentation

  • coolness, paleness, ulcers, hair loss, nail change

• ABI

  • to diagnoise asymptomatic disease

risk factor evaluation/modification

• smoking

• HTN

  • target < 130/80

• DM

• hyperlipidemia

• exercise

  • supervised programs more effective

  • walk 30 - 45 mins, 3x week for 3 - 6 months

  • 5 - 10 min warmup and cool down

  • set wroklat to induce moderate-severe pain in 3 - 5mins. rest until subside

T or F: everyone should be on antiplatelet for PAD

true

antiplatelet therapy drugs for PAD

• aspirin = 81 - 325 mg

• clopidogrel (Plavix) = 75 mg (alternative to aspirin)

anticaogulants for PAD

• not recommended

• low dose rivaroxaban (Xarelto) w/ low dose aspirin

  • increased risk of bleeding

Cilostazol (Pletal)

• indication

• MOA

• CI

• ADE

• DDI

• onset of action

• indication

  • intermittent claudication (increase walking distance w/o pain)

• MOA

  • phosphodiesterase III inhibitor (increase cAMP to inhibit reversibly platelet aggregation, cause vasiodolation, inhibit smooth muscle proliferation)

• CI

  • heart failure

• ADE

  • HA, loose stools, diarrhea, palpitations

• DDI

  • CYP3A4 and 2D16

• onset of action

  • weeks to months

critical limb ischemia

• chronic (< 2 weeks) inadequate blood flow to lower limbs

• rest pain, ulceration, gangrene, limb loss

• surgical revascularization and wound healing therapies

acute limb ischemia

• acute (< 2 weeks) inadequate resting blood flow to lower limb

• pain, pallor, pulselessness, paresthesias, paralysis, coolness

• emergency

• treat w/ systemic anticoagulation, reperfusion therapy

VTE

deep vein thrombosis (DVT)

• asymptomatic

• s/sx

  • pain, tenderness

  • swelling discoloration

  • edema

DVT diagnosis

• doppler ultrasound

• d-dimer

• venography

DVT complications

• post-thrombotic syndrome

  • treatment: compression stockings for up to 2 years

• PE

compression stockings

• apply graduated pressure to leg (greatest at ankle)

• challenges:

  • uncomfortable, hot , expensive

pulmonary embolism (PE)

• clinical presentation

• symptoms

• clinical presentation

  • depend on size/# of emboli, arteries involved, pt’s underlying disease

• symptoms

  • cough

  • chest pain

  • SOB

  • palpitation

  • other: hemopytysis, dizziness, hyoptension, tachy, cyanosis

PE diagnostic tests

• spiral CT scaln

• ventilation-perfusion radionuclide scan

• d-dimer

• pulmonary angiography

PE complications

• pulmonary hypertension

• right sided heart failure

• death

treatment for DVT and PE

• anticoagulation therapy

• IVC filters

additional therapy

• DVT

• PE

• DVT

  • compression therapy

  • early mobility

  • pain management

• PE

  • O2

  • throbomytic therapy or embolectomy

  • if needed

thrombolytic therapy

• indication

• goal

• agents

• important

• indication

  • hemodynamically unstable pts w/ large PE

    • hypotension (SBP < 90)

    • tachy

    • hypoxemia

    • evidence of right strain or dysfunction

• goal

  • lyse clot and restore hemodynamic function

• agents

  • Alteplase (Activase)

  • Tenecteplase (TNKase)

• important

  • anticoagulation therapy afterwards

cather-directed thrombolysis and thrombectomy/embolectomy

• indications

• requirements

• importance

• indications

  • higher risk PEs

  • pt w/ CI to systemic thrombolytics

  • large DVTs

• requirements

  • surgical expertise

• importance

  • not recommended to replace anticoagulation if not CI

catherter-directed thrombolysis

delivers lower dose thrombolytic directyl to embolus site

thrombectory/emobolectomy

can be used in combo w/ anticoagulation to reduce decompensation

IVC filters

• purpose

• indications

• diisadvantage

• purpose

  • short term protection when anticoagulation ineffective/unsafe

• indications

  • CI w/ anticoagulation

  • massive PE

  • recurrent VTE

• diisadvantage

  • increases long-term risk of VTE

primary prophylaxis

prevent formation of new clot

secondary prophylaxis

prevent extension of developed blood clot

parenteral anticoagulation agents

• UFH

• LMWH

• factor Xa inhibitor

• DTI

oral anticoagulation agents

• vitamin K antagonist

• factor Xa inhibitor

• DTI

UFH

• clinical applications

• dosing IV

• dosing SQ

• renal/liver dysfunction

• clinical applications

  • prophylaxis/treatment of DVT/PE

  • ACS

  • hip/knee surgery

• dosing IV

  • 80 - 100 units/kg bolus (max 10,000 units) → 18 - 20 units/kg/hr (max 2000 units/hr)

• dosing SQ

  • unmonitored

  • 333 units/kg → 250 units/kg ever 12 hrs

• renal/liver dysfunction

  • no adjustments needed

UFH monitoring

• aPTT or antifactor Xa levels

• drawn 6 - 8 hrs after starting dose and 6 -8 hrs after any dose change

• therapeutic range

  • aPPT: 1.5 - 2.5 X control

  • antifactor Xa: 0.3 - 0.7 units/mL

UFH side effects

• bleeding

• thrombocytopenia (HIT)

• osteoporosis

• hyperkalemia

LMWH

• clinical applications

• agents

• monitoring

• SEs

• clinical applications

  • prevention/treatment of DVT/PE

  • ACS

  • hip/knee surgery

• agents

  • Enoxaparin (Lovenox)

  • Dalteparin (Fragmin)

  • Tinzaparin (Innohep)

• monitoring

  • none

• SEs

  • similar to UFH but lower

Enoxaparin (Lovenox) dosing

• 1mg/kg SC every 12 hrs

• prophylaxis: 40 mg SC daily

factor Xa inhibitor: Parenteral

• fondaparinux (Arixtra)

  • SQ

  • for DVT prophylaxis, treatment of DVT/PE, ACS

factor Xa inhibitors: Oral (DOACs or NOACs)

• agents

• indications

• agents (-aban)

  • Rivaroxaban (Xarelto)

  • Apixaban (Eliquis)

  • Edoxaban (Sayvaysa)

• indications

  • treatment of DVT?PE

  • reduce recurrence risk

  • postoperative

  • a-fib

rivaroxaban (Xarelto) dosing

• VTE

• AF

• VTE

  • 15 mg PO BID 3x week → 20 mg PO daily

  • with food

• AF

  • 20 mg PO daily

Apixaban (Eliquis) dosing

• VTE

• AF

• VTE

  • 10 mg PO BID 1x week → 5 mg PO BID

• AF

  • 5 mg PO BID

Edoxaban (Sayvaysa) dosing

• VTE and AF

60 mg PO daily after 5 - 10 days of parenteral anticoagulant

renal insufficiency of factor Xa inhibitors

• apixaban (Eliquis)

• rivaroxaban (Xarelto)

• edoxaban (Sayvaysa)

• apixaban

  • used in any degree of dysfunction, including dialysis

• rivaroxaban

  • avoid if CrCl < 30 ml/min or dialysis

• edoxaban

  • lower dose if CrCl 15 - 50ml/min

  • avoid if CrCl < 15 ml/min

hepatic insuffiency in factor Xa inhibitors

• avoid in moderate-severe liver disease

• monitor LFTs (AST/ALT)

advantages of factor Xa inhibitors vs warfarin

• fixed dosing

• no monitoring required

• reduced incidence of HIT

• less drug/food interactions

disadvantages of factor Xa inhibitors vs warfarin

• no therapeutic range specified

• no preferred w/ renal insufficiency (except apixaban)

• avoid in pts w/ mechanical heart valve or antiphospholipid antibody syndrome

direct thrombin inhibitors (DTI)

• MOA

• parenteral agents

• oral agents

• MOA

  • inhibit thrombin

  • does not induce immune-mediated thrombocytopenia

  • can be used for HIT

• parenteral agents

  • Agratroban

  • Bivalirudin

• oral agents

  • Dabigatran (Pradaxa)

agratroban, bivalirudin

• indication

• difference

• IV dosing

• indication

  • HIT

  • ACS

• difference

  • argatroban: dose reduce in hepatic disease

  • bivalirudin: dose reduce in renal disease

• IV dosing

  • bolus → infusion

  • monitored by aPTT

  • can increase INR

Dabigatran (Pradaxa)

• indication

• VTE dosing

• CI

• storage and handling

• SEs

• indication

  • reduction in risk of recurrent VTE/PE

  • a-fib

• VTE dosing

  • 150 mg 2x daily after 5 - 10 days of pareteral anticoagulation

• CI

  • avoid in CrCl < 30 ml/min

  • dialysis

• storage and handling

  • in OG container

  • bottle open → use within 120 days

• SEs

  • GI upset

  • dyspepsia

  • → take w/ food

anticoagulant counseling

• avoid excessive alcohol → bleeding risk

• avoid NSAIDs and ASA → bleeding risk

• counsel on s/sx of bleeding

• adherence

BBW for anticoagulants

• neuraxial anesthesia

• hematomas

warfarin (Coumadin): vitamin K antagonist

• indications

• MOA

• PK

• monitoring

• indications

  • prophylaxis/treatment of DVT/PE

  • thromboembolic complcations w/ a-fib and cardiac valve replacement

  • reduce death/recurrence

• MOA

  • inhibit production of vitamin K dependent clotting factors

• PK

  • 36 hrs

  • DOA: 2 - 5 days

• monitoring

  • narrow therapeutic window

  • PT (time in sec for clot to form)

  • INR

INR monitoring frequency

• hopsitalized

  • checked daily

• outpatient

  • check 2x weekly

  • stable → every 4 weeks up to 12 weeks

  • dose change → check 7 - 14 days

warfarin

• CI/precautions

• ADE

• pt counseling

• CI/precautions

  • major bleed

  • inability to comply

  • pregnancy

  • risk of hemorrhage

  • warfarin-induced skin necrosis

• ADE

  • minor bleeding: bruising, nosebleeds, gum bleeds

  • major bleeding: pink urine, tarry stools, hemopytysis, drop in Hgb > 2 mg/dL

  • head trauma

• pt counseling

  • INR monitoring

  • how to take

  • bleeding s/sx and management

warfarin DDI

• CYP induction

• CYP inhibition

• managment

• CYP induction = decrease INR

  • Rifampin (2C9)

  • cigarette smoking (1A2)

  • phenytoin (3A4)

• CYP inhibition = increase INR, bleeding

  • amiodarone, -zoles (2C9)

  • ciprofloxacin (3A4)

• management

  • skip 1- 2 doses

  • adjust weekly dose

warfarin OTC drug interactions

• pain meds (safest is Tylenol)

• cimetidine

• bismuth subsalicylate

• vitamin K diet

• high fiber products (decreases warfarin effect)