AGGIORNAMENTI in CARDIOLOGIAF. BELLANDI U.O.CARDIOLOGIA OSPEDALE DI PRATO RISK SCORE STRATIFICATION...

AGGIORNAMENTI AGGIORNAMENTI in CARDIOLOGIAin CARDIOLOGIA

I NUOVI ANTICOAGULANTI ORALII NUOVI ANTICOAGULANTI ORALI

F. BELLANDIF. BELLANDI

U.O.CARDIOLOGIAU.O.CARDIOLOGIA

OSPEDALE DI PRATOOSPEDALE DI PRATO

RISK SCORERISK SCORESTRATIFICATIONSTRATIFICATION

NOVEL ORALNOVEL ORALANTICOAGULANTSANTICOAGULANTS

TRULY LOW RISK TRULY LOW RISK PATIENTSPATIENTS

3.23.23 3

2.692.692 2

1.751.751 1

0.840.840 0

Stroke/Stroke/thromboembolismthromboembolism rates at 1rates at 1--y y

followfollow--upupCHACHA 22DSDS22--VASc scoreVASc score

CHADS2 = 0

CHA2DS2-VASc = 0

CHA2DS2-VASc = 1

CHA2DS2-VASc = 2

CHA2DS2-VASc = 3

Olesen JB, et al 2012 Thromb Haemost

CHACHA22DSDS22--VASc vs CHADSVASc vs CHADS22

In In patientspatients withwith a CHA2DS2a CHA2DS2--VASc score of VASc score of 00 (i.e., (i.e., agedaged

3.23.23 3

2.692.692 2

1.751.751 1

0.840.840 0




Olesen JB, et al 2012 Thromb Haemost

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

AntithromboticAntithrombotic therapytherapy toto preventpreventthromboembolismthromboembolism isis recommendedrecommended

forfor allall patientspatients withwith AFAF, , exceptexcept in in thosethose patientspatients ((bothboth male and male and femalefemale ) )

whowho are at low are at low riskrisk ((agedaged

www.escardio.org/guidelines

ConnollyConnolly SJ, SJ, etet alal


WhenWhen patientspatients refuserefuse the the useuse of of anyany OAC OAC ((whetherwhether VKAsVKAs or or NOACsNOACs ), ), antiplateletantiplatelet

therapytherapy shouldshould bebe consideredconsidered ,,usingusing combinationcombination therapytherapy withwith

aspirinaspirin 7575––100 mg plus 100 mg plus clopidogrelclopidogrel75 mg 75 mg dailydaily ((wherewhere therethere isis a low a low riskrisk of of bleedingbleeding ) or ) or —— lessless effectivelyeffectively —— aspirinaspirin

7575––325 mg 325 mg dailydaily ..

ACTIVE ACTIVE InvestigatorsInvestigators


The The riskrisk of major of major bleedingbleeding withwithantiplateletantiplatelet therapytherapy ((withwith aspirinaspirin ––

clopidogrelclopidogrel combinationcombination therapytherapy and and ––especiallyespecially in the in the elderlyelderly –– alsoalso withwith

aspirinaspirin monotherapymonotherapy ) ) shouldshould bebeconsideredconsidered asas beingbeing similarsimilar toto OACOAC


The The choicechoice of of antithromboticantithrombotic therapytherapyshouldshould bebe basedbased uponupon the the absoluteabsolute

risksrisks of of strokestroke //thromboembolismthromboembolism and and bleedingbleeding and the and the net net clinicalclinical

benefitbenefit forfor a a givengiven patientpatient

CHACHA22DSDS22--VASc scoreVASc scoreimplementationimplementation


The CHAThe CHA 22DSDS22--VASc score VASc score isisrecommendedrecommended asas a a meansmeans of of assessingassessing strokestroke riskrisk in in nonnon --

valvularvalvular AFAF


♀♀ 70 aa +malattia coronarica

♀♀ 50 aa +diabete

CHADS2 = 0 CHADS2 = 1

CHA2DS2-VASc = 3 CHA2DS2-VASc = 1


In patients with a CHA 2DS2-VASc score of 11, OAC therapy with

• adjusted-dose VKA (INR 2–3); or• a direct thrombin inhibitor (dabigatran); or• an oral factor Xa inhibitor (e.g. rivaroxaban, apixaban)

…. shouldshould bebe consideredconsidered, based upon anassessment of the riskrisk of of bleedingbleeding complicationscomplicationsand patient preferences


AssessmentAssessment of the of the riskrisk of of bleedingbleeding isisrecommendedrecommended whenwhen prescribingprescribing

antithromboticantithrombotic therapytherapy ((whetherwhether withwith VKA, VKA, NOAC, NOAC, aspirinaspirin //clopidogrelclopidogrel , or , or aspirinaspirin ).).

The The HASHAS--BLEDBLED scorescore shouldshould bebe consideredconsidered asas a a calculationcalculation toto assessassess bleedingbleeding riskrisk ,, wherebywhereby a score a score ≥≥3 3

indicatesindicates ‘‘high high riskrisk ’’ and some and some cautioncaution and regular and regular reviewreview isisneededneeded , , followingfollowing the the initiationinitiation of of antithromboticantithrombotic therapytherapy , ,

whetherwhether withwith OAC or OAC or antiplateletantiplatelet therapytherapy



Correctable risk factors for bleeding [e.g. uncontrolled blood pressure, labile INRs if the patientwas on a VKA, concomitant drugs (aspirin, NSAIDs,

etc.), alcohol, etc.] should be addressed


Use of the HAS-BLED score should beused to identify modifiable bleeding risksthat need to be addressed, butbut shouldshouldnotnot bebe usedused on on itsits ownown toto excludeexclude

patientspatients fromfrom OAC OAC therapytherapy

NOACsNOACs ((dabigatrandabigatran , , rivaroxabanrivaroxaban , and , and apixabanapixaban ) ) are are notnot recommendedrecommended in in patientspatientswithwith severe severe renalrenal impairmentimpairment

((CrClCrCl


BaselineBaseline and and subsequentsubsequent regular regular assessmentassessment of of renalrenal functionfunction ((byby CrClCrCl ) ) isis

recommendedrecommended in in patientspatients followingfollowinginitiationinitiation of of anyany NOAC, NOAC, whichwhich shouldshould bebe

donedone annuallyannually butbut more more frequentlyfrequently in in thosethosewithwith moderate moderate renalrenal impairmentimpairment wherewhere CrClCrCl

shouldshould bebe assessedassessed 22––3 3 timestimes per per yearyear

HR:0.59

HR:0.26

Adapted from Hart R, et al Ann Intern Med 2007

a. Fang MC, et al Am J Med 2007

NOVEL ORAL ANTICOAGULANTS

= EFFICACY= EFFICACYSAFETYSAFETY

50-50-50 rule

PtsPts warfarinwarfarin suitablesuitable

50% don't get on it

50-50-50 rule


50% percent of those who do get on it, stop itstop it

50-50-50 rule


At least 50%50% of those remaining are not in the therapeutic rangeare not in the therapeutic range

50-50-50 rule


about 12.5%12.5% are correctlycorrectly treated with warfarinwarfarin

3.23.23 3

2.692.692 2

1.751.751 1

0.840.840 0



NOVEL ORAL ANTICOAGULANTSNOVEL ORAL ANTICOAGULANTS

ALMENO UNA DELLE ALMENO UNA DELLE TRETRE CONDIZIONICONDIZIONI:

1) score1) score CHACHA 22DSDS22VASc VASc ≥≥ 1 con HAS1 con HAS--BLED > 3BLED > 3

DABIGATRANDABIGATRAN

2) paziente gipaziente giàà in trattamento con un antagonista della vitamina K in trattamento con un antagonista della vitamina K ((coumadincoumadin o derivati)o derivati) se il tempo trascorso nel se il tempo trascorso nel rangerangeterapeutico (TTR) negli ultimi 6 mesi, terapeutico (TTR) negli ultimi 6 mesi, èè ≤≤ 70%70%

3) Il trattamento anticoagulante con antagonisti della 3) Il trattamento anticoagulante con antagonisti della vitamina K non vitamina K non èè attuabile per difficoltattuabile per difficolt àà oggettive ad oggettive ad eseguire i controlli di INR (eseguire i controlli di INR (eses:: i pazienti che eseguono i i pazienti che eseguono i prelievi domiciliari)prelievi domiciliari)

Differenze con DABIGATRANDifferenze con DABIGATRAN :

1) score1) score CHA2DS2VASc CHA2DS2VASc >> 3 3 con HAScon HAS--BLED > 3BLED > 3

RIVAROXABANRIVAROXABAN

2) paziente gipaziente giàà in trattamento con un antagonista della vitamina K in trattamento con un antagonista della vitamina K ((coumadincoumadin o derivati)o derivati) se il tempo trascorso nel se il tempo trascorso nel rangerangeterapeutico (TTR) negli ultimi 6 mesi, terapeutico (TTR) negli ultimi 6 mesi, èè ≤≤ 60%60%

3) Prescrivibile solo per la FANV PERMANENTE 3) Prescrivibile solo per la FANV PERMANENTE mentre il mentre il DabigatranDabigatran per tutte le forme di FANVper tutte le forme di FANV

Alterata funzionalitAlterata funzionalit àà renale = creatinina > 2.3 mg/dlrenale = creatinina > 2.3 mg/dl

Alterata funzionalitAlterata funzionalit àà epatica = epatica = ↑↑ bilirubina x 2 e/obilirubina x 2 e/o↑↑ transaminasi x 3transaminasi x 3

DABIGATRANDABIGATRAN (Pradaxa) 150 mg 1 cps x 2/dieRIVAROXABAN RIVAROXABAN (Xarelto) 20 mg 1 cp/die

MINORE RISCHIO EMORRAGICO

a) Creatinina clearance > 50 ml/minb) Età < 75 aac) Peso > 50 Kg

DABIGATRANDABIGATRAN (Pradaxa) 110 mg 1 cps x 2/dieRIVAROXABANRIVAROXABAN (Xarelto) 15 mg 1 cp/die

MAGGIORE RISCHIO EMORRAGICO

a) Creatinina clearance > 30 e < 50 ml/minb) Età > 75 aac) Peso < 50 Kg

Switching Patients From Switching Patients From WarfarinWarfarin to New Oral Anticoagulantsto New Oral Anticoagulants

• WARFARIN HALF LIFE 36-40 hours

• If the new agent is initiated too soon after discon tinuing warfarin, the risk for bleeding increases due to an overlap of an ticoagulation effect

• if initiation of the new agent is delayed, then the risk for thrombosis increases.

THE TIMING OF INITIATION OF THE NEW AGENT IS VERY IMPORTANT

to ensure safe and effective anticoagulationto ensure safe and effective anticoagulation

• Dabigatran may be initiated when the INR is less than 2.3, which is based on the study protocol of RE-LY

• Rivaroxaban may be initiated when the INR is 3.0, based on the ROCKET AF study

• However, most clinicians would prefer the INR to be 2.5 and fallHowever, most clinicians would prefer the INR to be 2.5 and fall ing prior to ing prior to commencing commencing rivaroxabanrivaroxaban

Switching Patients From New Oral Anticoagulants to Switching Patients From New Oral Anticoagulants to WarfarinWarfarin

DELAYEDDELAYEDACTIONACTION

WARFARINWARFARIN

HALFHALF --LIFELIFENOACsNOACs

RENALRENALFUNCTIONFUNCTION

OVERLAP PERIODOVERLAP PERIOD

•• DECLINING RENAL FUNCTION, SHORTER OVERLAP PERIODDECLINING RENAL FUNCTION, SHORTER OVERLAP PERIOD

•• LONGER NOAC HALFLONGER NOAC HALF --LIFE, SHORTER OVERLAP PERIODLIFE, SHORTER OVERLAP PERIOD

Switching Patients From New Oral Anticoagulants to Switching Patients From New Oral Anticoagulants to WarfarinWarfarin

DayDay 22DayDay 1115-30

DayDay 33DayDay 2231-50

DayDay 44DayDay 33>50

RivaroxabanRivaroxabanDabigatranDabigatranCalculated CrCL, mL/min

OVERLAP PERIODOVERLAP PERIOD

The longer overlap with The longer overlap with rivaroxabanrivaroxaban is justified by its halfis justified by its half --life being life being shorter than that of shorter than that of dabigatrandabigatran

• It is important to note that both It is important to note that both dabigatrandabigatran and and rivaroxabanrivaroxabanmay affect the INR; thus, for a reliable determination of INR, may affect the INR; thus, for a reliable determination of INR, measuring should be performed at least 2 to 3 days after measuring should be performed at least 2 to 3 days after discontinuing the new oral agent.discontinuing the new oral agent.

ManagingManaging OralOral AnticoagulantsAnticoagulants in the in the PerioperativePerioperative SettingSetting

BLEEDINGBLEEDINGRISK OFRISK OF

SURGERYSURGERY

HALFHALF --LIFELIFENOACsNOACs

RENALRENALFUNCTIONFUNCTION

timing of timing of discontinuationdiscontinuation

declining renal functiondeclining renal function , , longer NOAC halflonger NOAC half --lifelife and a and a higher higher risk for bleedingrisk for bleeding , a , a longerlonger duration of interruption may be neededduration of interruption may be needed

ManagingManaging OralOral AnticoagulantsAnticoagulants in the in the PerioperativePerioperative SettingSetting

4 d4 d2 d2 dUnknownUnknown< 30< 302 d2 d24 h24 h12 (1112 (11--13)13)> 30> 30

RivaroxabanRivaroxaban

6 d6 d4 d4 d27 (2227 (22--35)35)≤≤ 30304 d4 d2 d2 d18 (1318 (13--23)23)> 30 > 30 toto ≤≤ 50502 d2 d24 h24 h15 (1215 (12--34)34)> 50 > 50 toto ≤≤ 80802 d2 d24 h24 h13 (1113 (11--22)22)> 80> 80

DabigatranDabigatran

High High RiskRisk forforBleedingBleeding bb

Standard Standard RiskRisk forforBleedingBleeding aa

Timing of Discontinuation AfterTiming of Discontinuation AfterLast Dose Before SurgeryLast Dose Before SurgeryHalfHalf --LifeLife (h, (h,

rangerange ))Renal FunctionRenal Function((CrCLCrCL , ml/min), ml/min)

a)a) Cardiac catheterization, colonoscopy without removal of large poCardiac catheterization, colonoscopy without removal of large polyps, and lyps, and uncomplicated laparoscopic procedures, such as uncomplicated laparoscopic procedures, such as cholecystectomycholecystectomy

b) Major cardiac surgery, insertion of pacemakers or defibrillatb) Major cardiac surgery, insertion of pacemakers or defibrillators (resulting ors (resulting from the risk for pocket hematoma), neurosurgery, large hernia sfrom the risk for pocket hematoma), neurosurgery, large hernia surgery, and urgery, and major cancer/urologic/vascular surgerymajor cancer/urologic/vascular surgery.

RivaroxabanRivaroxaban and and apixabanapixaban undergo partial metabolism in the liver via the undergo partial metabolism in the liver via the CYP450 pathway (CYP3A4)CYP450 pathway (CYP3A4)

All 3 agents are substrates of PAll 3 agents are substrates of P--glycoprotein transporterglycoprotein transporter

RecommendationsRecommendations forfor preventionprevention of of thromboembolismthromboembolism in in nonnon --valvularvalvular AF AF —— periperi --cardioversioncardioversion

ForFor patientspatients withwith AF of AF of ≥≥48 h 48 h durationduration , or , or whenwhenthe the durationduration of AF of AF isis unknownunknown , OAC , OAC therapytherapy

(e.g. VKA (e.g. VKA withwith INR 2INR 2--3 or 3 or dabigatrandabigatran ) ) isisrecommendedrecommended forfor ≥≥3 3 weeksweeks priorprior toto and and forfor ≥≥4 4 weeksweeks after after cardioversioncardioversion , , regardlessregardless of the of the

methodmethod ((electricalelectrical or or oraloral //i.v.i.v. pharmacologicalpharmacological ))


RecommendationsRecommendations forfor LAA LAA closureclosure


InterventionalInterventional , , percutaneouspercutaneous LAA LAA closureclosuremaymay bebe consideredconsidered in in patientspatients withwith a high a high

strokestroke riskrisk and and contraindicationscontraindications forforlongtermlongterm oraloral anticoagulationanticoagulation


AntithromboticAntithrombotic therapytherapy toto preventprevent thromboembolismthromboembolism isisrecommendedrecommended forfor allall patientspatients withwith AFAF, , exceptexcept in in thosethose patientspatients((bothboth male and male and femalefemale ) ) whowho are at low are at low riskrisk ((agedaged

In patients with a CHA 2DS2-VASc score of 11, and

in patients with a CHA 2DS2-VASc score of ≥ 2

OAC therapy with:• adjusted-dose VKA (INR 2–3); or• a direct thrombin inhibitor (dabigatran); or• an oral factor Xa inhibitor (e.g. rivaroxaban, apixaban)…. shouldshould bebe consideredconsidered ((……isis recommendedrecommended ))




AspirinAspirin plus plus clopidogrelclopidogrel or or —— lessless effectivelyeffectively —— aspirinaspirin whenwhenpatientspatients refuserefuse the the useuse of of anyany OAC (OAC (whetherwhether VKAsVKAs or or NOACsNOACs ), ), shouldshould bebe consideredconsidered ..

AGGIORNAMENTI in CARDIOLOGIAF. BELLANDI U.O.CARDIOLOGIA OSPEDALE DI PRATO RISK SCORE STRATIFICATION...

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Transcript of AGGIORNAMENTI in CARDIOLOGIAF. BELLANDI U.O.CARDIOLOGIA OSPEDALE DI PRATO RISK SCORE STRATIFICATION...