effectiveness and safety of oral anticoagulation with non ... pengo.pdf · embolia polmonare . ......

Effectiveness and safety of oral anticoagulation with non-vitamin K antagonists compared to well-managed vitamin K antagonists in naïve

patients with non-valvular atrial fibrillation: Propensity score matched cohort study

Gentian Denas a, Nicola Gennaro b, Eliana Ferroni b, Ugo Fedeli b, Mario Saugob, Giacomo Zoppellaro a, Seena Padayattil Jose a, Giorgio Costa c, Maria Chiara Corti b, Margherita Andretta c, Vittorio Pengo a,⁎ a Cardiology Clinic, Department of Cardiac, Thoracic and Vascular Sciences, Padua University Hospital

b Epidemiological Department (SER), Veneto Region, Padua, Italy c Unified Pharmaceutical Coordination Centre (CRUF), Veneto Region, Venice, Italy

International Journal of Cardiology 2017 (in press)

Obiettivo del Progetto

Costruzione di un database per il monitoraggio degli eventi tromboembolici ed emorragici dei pazienti residenti nella Regione del Veneto con fibrillazione atriale non valvolare in terapia anticoagulante orale (NAO e AVK)

Anagrafe Regionale

Farmaceutica territoriale

Farmaceutica Diretta/p.c.

SDO

Flussi Informativi della Regione Veneto

collegabili attraverso un identificativo anonimo

Anagrafe Esenzioni

Courtesy of Nicola Gennaro, SER Veneto

Anagrafe Regionale



SDO



Selezione: • ATC: B01AA03 B01AA07 B01AE07

B01AF01 B01AF02 (Con l'esclusione dei seguenti MinSan: 038451011 038451023 038744064 038744076 038744052)

• Data di prescrizione compresa dal 1/7/2013 al 31/12/2015

Scatole Ricette

Codici identificativi

Pazienti non istituzionalizzati

identificati

Anagrafe Esenzioni

Case di riposo dati aggregati


Anagrafe Regionale



SDO



Pazienti identificati

Anagrafe Esenzioni

Esclusione Trombosi Venosa Profonda Stenosi mitralica Embolia polmonare Chirurgia cardiovascolare (esclusa la bioprotesi aortica)

Esclusione Residenti fuori dal Veneto

Pazienti con Fibrillazione Atriale

non valvolare Courtesy of Nicola Gennaro, SER Veneto

Anagrafe Regionale



SDO



FA non valvolare

Anagrafe Esenzioni

Esclusione Uso precedente di anticoagulanti orali (1 anno) Uso di anti piastrinici durante il follow-up

Pazienti naïve


Anagrafe Regionale





Coorte in studio 40.411

Tempo Baseline

Follow-up

Caratterizzazione • Sesso ed età • Comorbosità • Terapie

SDO Anagrafe Esenzioni

• Morte • Infarto del miocardio • Ictus • Tutti i sanguinamenti • Sanguinamento intracranico



Anagrafe Regionale





Tempo Baseline


Follow-up




Anagrafe Regionale






Tempo Baseline


Follow-up




Anagrafe Regionale





Tempo Baseline



Follow-up




Anagrafe Regionale






Tempo Baseline


Follow-up




NOACs: pazienti più vecchi, più femmine, CHADSVASC più alto soprattutto per pregresso stroke, Più storia di sanguinamenti meno scompenso cardiaco, meno diabete, meno insufficienza renale

Crude effectiveness Despite the higher risk for ischaemic stroke in the NOACs group (higher CHA2DS2VASc score), we found equal crude effectiveness of NOACs versus VKAs

Crude safety

Despite the good control of anticoagulation and a higher risk of bleeding (HASBED) with VKAs, we found a better safety with NOACs

The rate of major bleeding in the VKA group is in line with that reported for well-controlled anticoagulation and stems for • A good clinical and laboratory control of treatment in our region • Goodness of our extracted data

Analisi “Intention to treat” (ITT) 01-07-2013 31-12-2015 31-03-2016

M

Escluso

S M

Periodo di reclutamento

1)

2) 3)

4)

Anno di osservazione ante l’arruolamento AVK NAO M

S Morto Sanguinamento Tempo persona


Analisi ”as treated” 01-07-2013 31-12-2015 31-03-2016

M

Escluso

S M

Periodo di reclutamento

Anno di osservazione ante l’arruolamento AVK NAO M

S Morto Sanguinamento Tempo persona

1)

2) 3)

4)

Numero di giorni in trattamento(DDD) + Finestra di 60 gg


Conclusioni

• I NOACs vengono preferenzialmente prescritti a pazienti più anziani con pregresso stroke e storia di sanguinamenti (sono ritenuti più sicuri)

• I risultati sia della analisi intention to treat (efficacia in termini di salute pubblica) che quella as treated (efficacia in base alla aderenza) sembrano favorevoli ai NOACs nonostante il boun controllo dell’anticoagulazione nel gruppo warfarin.

Why we need real life data?

Real life studies for NOACs

25 31 30

58 61

93

134 140

79

2009 2010 2011 2012 2013 2014 2015 2016 May, 2017

• Context Selective eligibility criteria of randomized controlled trials (RCTs) are vital to trial feasibility and internal validity. However, the exclusion of certain patient populations may lead to impaired generalizability of results.

• Conclusions …Women, children, the elderly, and those with common medical conditions are frequently excluded from RCTs. … Such exclusions may impair the generalizability of RCT results. These findings highlight a need for careful consideration and transparent reporting and justification of exclusion criteria in clinical trials.

TABELLA DELLE CODIFICHE

Real life data in the Veneto healthcare environment

• A consistent number of thrombosis centres monitor VKA-treatment • Patients are maintained into the appropriate INR interval for a good

period of time (TTR = 68%)

• The clinical advantage of using NOACs in an area well covered by thrombosis centres (Veneto Region) where the clinical and laboratory control of VKA-treatment is optimal, might be minimal

NOAC vs VKA population

• Anticoagulant use increases with increasing age … until 85 years!

• VKAs are predominant in < 85 years while NOACs predominate >85 year-group and females

• CHF, diabetes and renal disease patients receive more VKAs

• Higher risk patients (both TE and bleeding) receive NOACs

Impossibile visualizzare l'immagine. La memoria del computer potrebbe essere insufficiente per aprire l'immagine oppure l'immagine potrebbe essere danneggiata. Riavviare il computer e aprire di nuovo il file. Se viene visualizzata di nuovo la x rossa, potrebbe essere necessario eliminare l'immagine e inserirla di nuovo.

Propensity matching

• We performed robust propensity score–weighted analysis to minimize potential confounding due to the very different patient characteristics

• A large number of variables were taken into account (from 40411 patients to 6740 patients)

• Comparative analysis of end-points were performed using stratified and one-to-one matched analysis and according to ITT and as treated approaches

• Intention to treat: more pertinent for the evaluation of effectiveness in terms of the public health impact with the introduction of new drugs

• As treated approach we sought for treatment effect according to adherence

Safety of NOACs maintained even with propensity score

Mortality and myocardial infarction

• A reduction in death rates with NOACs was found confirming reported data in the literature

• No difference in the incidence of myocardial infarction was observed between NOAC and VKA treated individuals

Conclusions

• Superior safety of NOACs even against optimal VKA therapy • Clearly, a good performance of VKA-treatment might have further reduced

the relative benefit of NOACs in terms of bleeding complications

• Overall positive global impact of NOACs’ with respect to safety and possibly mortality

• NOACs performed better even with older and higher risk patients • Comorbidities that would have actually biased the results in VKAs’ favour

effectiveness and safety of oral anticoagulation with non ... pengo.pdf · embolia polmonare . ......

Documents