PROPRIETA’ GENERALI
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Transcript of PROPRIETA’ GENERALI
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Metodi di valutazione della sincronizzazione
ventricolare e loro affidabilità
G. Lupi, ASL IV Chiavarese
NUOVI ANTICOAGULANTI ORALI: DAI GRANDI TRIAL ALLE SCELTE CLINICHE
PERSONALIZZATE : APIXABAN
G Lupi, Dipartimento di Cardiologia ASL 3 Genovese
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PROPRIETA’ GENERALI
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INDICATIONS
• Apixaban is recommended as an option for preventing stroke and systemic embolism in people with nonvalvular atrial fibrillation with 1 or more risk factors such as:
• prior stroke or transient ischaemic attack• age 75 years or older• hypertension• diabetes mellitus• symptomatic heart failure.
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• Patients with AF who have stroke risk factor(s) ≥1 are recommended to receive effective stroke prevention therapy, which is essentially OAC
• The evidence for effective stroke prevention with aspirin in AF is weak, with a potential for harm
• The use of antiplatelet therapy … for stroke prevention in AF should be limited to the few patients who refuse any form of OAC.
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Of the whole study population (n=6036)
•46% of the patients received OAC,• 37.5% 1 antiplatelet agent• 16.5% received no antithrombotic therapy• 44.4% of the patients who did not receive warfarin presented with valid reasons not to be treated (side effects, refusal, no compliance, risk of bleeding)
Am J Cardiol 2013
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•A study comparing the safety and efficacy of apixaban and aspirin in patients with AF
• 5600 patients with AF unsuitable for or intolerant of warfarin Randomized to 5 mg of apixaban or 81 to 324 mg of aspirin for up to 36 months or until end of study
• Primary efficacy outcome: time from the first dose of the study drug to the first occurrence of ischemic stroke, hemorrhagic stroke, or systemic embolism
• Secondary efficacy outcome: time to the first occurrence of ischemic stroke, hemorrhagic stroke, systemic embolism, MI, or vascular death
S Connolly (McMaster UCongressniversity, Hamilton, ON)
AVERROES (Apixaban versus Acetylsalicylic Acid to Prevent Strokes)
AF=atrial fibrillation
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Warfarin (target INR 2-3)
Apixaban 5 mg oral twice daily(2.5 mg BID in selected patients)
Primary outcome: stroke or systemic embolism
Hierarchical testing: non-inferiority for primary outcome, superiority for primary outcome, major bleeding, death
Randomizedouble blind,
double dummy(n = 18,201)
Inclusion risk factors Age ≥ 75 years Prior stroke, TIA, or SE HF or LVEF ≤ 40% Diabetes mellitus Hypertension
Warfarin/warfarin placebo adjusted by INR/sham INR based on encrypted point-of-care testing device
Major exclusion criteria Mechanical prosthetic valve Severe renal insufficiency Need for aspirin plus
thienopyridine
ARISTOTLE Atrial Fibrillation with at Least One Additional Risk Factor
for Stroke
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Primary OutcomeStroke (ischemic or hemorrhagic) or systemic embolism
Apixaban 212 patients, 1.27% per year Warfarin 265 patients, 1.60% per yearHR 0.79 (95% CI, 0.66–0.95); P (superiority)=0.011
No. at RiskApixaban 9120 8726 8440 6051 3464 1754Warfarin 9081 8620 8301 5972 3405 1768
P (non-inferiority)<0.001
21% RRR
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Major BleedingISTH definition
Apixaban 327 patients, 2.13% per year Warfarin 462 patients, 3.09% per yearHR 0.69 (95% CI, 0.60–0.80); P<0.001
No. at RiskApixaban 9088 8103 7564 5365 3048 1515Warfarin 9052 7910 7335 5196 2956 1491
31% RRR
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• 6 Strokes
• 15 Major bleeds
• 8 Deaths
Compared with warfarin, apixaban (over 1.8 years) prevented
per 1000 patients treated.
4 hemorrhagic 2 ischemic/uncertain type
ARISTOTLE
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Jama neurology 2013
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RENAL FAILURE
Hohnloser et al, European Heart Journal 2012
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COST-EFFECTIVENESS
The Committee concluded that :
•apixaban had been shown to be cost effective compared with warfarin, the most plausible ICER being less than £20,000 per QALY gained, and could be recommended as an option for preventing stoke and systemic embolism for people with nonvalvular atrial fibrillation who have 1 or more risk factors for stroke.• there was insufficient evidence to distinguish between the cost effectiveness of apixaban, dabigatran and rivaroxaban at this time.
NICE technology appraisal guidance 275
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UNCERTAINTY
•TRANSIENT ISCHAEMIC ATTACK
•HEALTH-RELATED QUALITY OF LIFE
•NO ADVANTAGE ON GASTROINTESTINAL BLEEDING
•NO DATA ON CARDIOVERSION
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Piano terapeutico
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PIANO TERAPEUTICO 2
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URGENZE• EMORRAGIA: -NON ESISTE ANTIDOTO-CARBONE VEGETALE-PLASMA FRESCO CONGELATO-FATTORE VIIa• SOVRADOSAGGIO:-50 mg/DIE X 7GG :NESSUN PROBLEMA-CARBONE : RIDUZIONE AUC DEL 50%
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In the population for whom warfarin was suitable,the ICER for apixaban compared with warfarin was £12757 per QALY gained. in a population for whom warfarin was unsuitable apixaban was associated with an ICER of £2903 per QALY gained compared with aspirin.
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ARISTOTLE
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Potente inibitore, reversibile, diretto e altamente selettivo del sito attivo del fattore Xa libero e legato
Non necessita dell'antitrombina III per esercitare l'attività antitrombotica;
non ha effetti diretti sull'aggregazione piastrinica, ma inibisce indirettamente l'aggregazione piastrinica indotta dalla trombina.
L'attività anti-Xa è, a diverse dosi, in rapporto lineare diretto con la concentrazione plasmatica, raggiungendo i valori massimi allo steady-state
APIXABAN (Eliquis®)
.