CARDIO FINAL TSU HYPERLIPIDEMIA AND VTE

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)

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

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)

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

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

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)

warfarin vitamin interactions

• multivitamins (may contain vit K)

• vitamin C

• vitamin E

• herbal products

warfarin

• alcohol

• smoking

• vitamin K

• alcohol

  • decreases INR

  • great risk of bleeding

  • avoid excessive drinking

• smoking

  • increased warfarin metabolism → decreased effect

• vitamin K

  • reverse warfarin activity

warfarin and disease states: increases INR

• hyperthyroidism

• fever

• heart failure

• liver disease

warfarin and disease states: decreases INR

hypothyroidism

onset of action warfarin

4 - 5 days (delayed onset)

overlap therapy

overlap warfarin w/ injectable anticoagulant (LMWH or UFH) until warfarin reached full effect (INR 2- 3) for at least 5 days

warfarin dosing

1 - 10 mg daily (5 mg common)

INR below 2

increase weekly dose

INR above 3

• decrease dose

• hold dose + decrease weekly dose

• follow up 7 - 14 days if change needed

duration of anticoagulation

• 1st DVT/PE

• > 1 episode of DVT or PE

• cancer-associated

• DVT/PE w/ high bleeding risk

• secondary prevention

• 1st DVT/PE

  • 3 months

• > 1 episode of DVT or PE

  • long term (6 - 12 months)

• cancer-associated

  • indefinite until cancer resolved

  • LMWH/DOAC

• DVT/PE w/ high bleeding risk

  • 3months

• secondary prevention

  • lower dose apixaban after 6 months

  • warfarin INR 2- 3

medical VTE prophylaxis

• nonpharm

• pharm

• nonpharm

  • compression socks

  • intermittent penumatic compression devices

• pharm

  • UFH 5000 units SC q8 - 12 h

  • enoxaparin 40 mg SC daily

  • fondaparinux 2.5 mg SC daily

surgical prophylaxis

• high risk VTE after surgeries

• pharm prophylaxis > mechanical

• risk of bleeding

• orthopedic surgery

  • aspirin, DOACs, LMWH at least 10 - 14 days after surgery

warfarin procedure managment

• discontinuation

• oral vitamin K

• restart

• dental procedure

• discontinuation

  • at least 5 days prior to preocedure to reach INR < 1.5

• oral vitamin K

  • given 1 - 2 days prior in INR elevated

• restart

  • `12 - 24 hrs after surgery

• dental procedure

  • dont stop warfarin

heparins and DOACs procedure management

• LMWH (SQ)

• UFK (IV)

• DOACs

• LMWH (SQ)

  • last dose 24 h before surgery

  • restart 24 - 72 h after surgery

• UFK (IV)

  • stop 4 hrs before surgery

  • restart 24 - 72 h after surgery

• DOACs

  • discontinue 1 - 2 days prior

bridging therapy

used when warfarin must be stopped

reversal agents

• packed RBCs

• FFP

• rVIIa

• PCC

• vitamin K

• protamin sulfate

• idaruzimab

• andexanet alfa

which reverses warfarin

• packed RBCs

• FFP

• rVIIa

• PCC

• vitamin K

which reverses UFH (fully) and enoxaparin (partially)

protamine sulfate

which reverse dabigatran

idaruzimab (Praxbind)

which reduced rivaroxaban and apixaban

andexanet alfa (discontinued)

INR above therapeutic but < 4.5

lower dose or omit 1 - 2 doses

INR 4.5 - 10

omit 1 -2 dsoes

low dose vitamin K considered

INR 10+

hold off warfarin

administer vitamin K

pregnancy

• DOC

• caution

• monitoring

• DOC

  • LMWH or UFH

• caution

  • last trimester and peripartum due to risk of hemorrhage

• monitoring

  • antiXa levels

DOC for children

UFK or LMWH