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

PROPRIETA’ GENERALI

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.

• 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.

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

•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

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

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

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

• 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

Jama neurology 2013

RENAL FAILURE

Hohnloser et al, European Heart Journal 2012

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

UNCERTAINTY

•TRANSIENT ISCHAEMIC ATTACK

•HEALTH-RELATED QUALITY OF LIFE

•NO ADVANTAGE ON GASTROINTESTINAL BLEEDING

•NO DATA ON CARDIOVERSION

Piano terapeutico

PIANO TERAPEUTICO 2

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%

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.

ARISTOTLE

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®)

.