NOACs Scegliere in Contesti Particolari

Transcription

1 Gianluca Botto, FESC, FEHRA U.O.s. Elettrofisiologia ASST-Lariana, Como NOACs Scegliere in Contesti Particolari

2 Presenter Disclosure Information Research support: Boston Scientific, Medtronic; St. Jude Medical, Bayer Healthcare, Gilead, Sanofi Advisory Board: Medtronic; St. Jude Medical, MSD, Bayer Healthcare, Boehringer, BMS, Pfizer, Daijchi, Sanofi Speaker Fees: Boston Scientific, Medtronic, St. Jude Medical, Sorin Group, Bayer Healthcare, Boehringer, BMS, Pfizer, Meda, MSD, Sanofi, Cardiome 2016 JAN

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4 Which Drug for Which Patient?

5 Pts vs Warfarin Mean 2,1 Mean 3,5 Mean 2,1 Mean 2,8

6 Target Characteristics of NOAs Comparison With Warfarin WARFARIN DABIGATRAN RIVAROXABAN APIXABAN EDOXABAN Vitamin K-dep. clotting factors II, VII, IX,and X Thrombin Factor Xa Factor Xa Factor Xa Bioavailability (%) >95 6 >80 (with food) >50 >60 (85 with food) Intake with food recommended? Absorption with H2B/PPI? Time to peak activity (hs) NO NO Mandatory NO No official recommendation NO -12%-30% NO NO NO , Half life (hs) (young healty) (elderly) Dosing frequency OD BID OD BID OD Interaction with drugs Interaction with food Several drugs including substrates of CYP2C9, CYP3A4, CYP1A2 Strong P-gp inhibitors and inducers Strong CYP3A4 inducers, strong inhibitors of both CYP3A4 and P-gp Strong inhibitors and inducers of both CYP3A4 and P-gp Strong P-gp inhibitors and inducers YES NO NO NO NO Renal elim (%) < (66) 27 50

7 What to Do in Patient with CKD?

8 Clin Pharmacokinet 2010; 49:

9 German prospective, non-interventional NOAC Reg. Rates, management and outcome of rivaroxabanrelated bleeding events analysed (n=1776) Apr 2012

10 NOACs Cessation Before Planned Surgery Heidbuchel H. EHRA Practical GL. Europace 2015; 17,

11 Drug Interaction

12 Drug-Drug Interaction Dose Adjustments With NOACs

13 Dose Reduction

14 Dosing Considerations Update D A E R DABI APIX EDOX RIVA % (EDO): age no significant effect after adjusting for weight and renal function Heidbuchel H. Eur Heart J 2015

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16 Incidence rate, %/year* XANTUS: Outcomes According to Dosing (20/15 mg od) Major bleeding, all-cause death and thromboembolic events (stroke/se/tia/mi) occurred at higher incidence rates for the 15 mg od versus the 20 mg od dose 4,0 3,5 3,0 2,5 2,0 1,5 1,0 0,5 0,0 15 mg dose 3,7 20 mg dose 3,1 2,3 1,8 1,6 1,4 Thromboembolic events Major bleeding All-cause death Dosing decisions may have been based on other clinical considerations besides impaired renal function *Events per 100 patient-years Camm AJ et al, Eur Heart J 2015; doi: /eurheartj/ehv466;

17 How Are DOACs Prescribed in the Real Word? Fay MR et al. ESC Scientific Session.2016; Poster P2597

18 Real-World Evidence Of Stroke Prevention In Pts With NVAF GI. Coleman, M. Antz (USA-Germany) ESC Rome 2016

19 Adherence

20 JAMA. 2015; 313:

21 Daily Dosing Frequency and Adherence Among NVAF Pts 26% higher likelihood of adherence with OD dosing regimen

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24 Nonadherence to a NOAC is Associate to Worse Outcomes

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26 Bleeding incidence (%) Bleeding Risk With Edoxaban Once-daily vd Twice-daily Dosing Total Major 18,3 12,7 7,3 5,5 3, ,4 30 mg OD 60 mg OD 30 mg BID 60 mg BID Edoxaban dose and regimens Weitz JI. Thromb Haemost 2010; 104:

27 Vrijens B. Europace : Non-vitamin K Antagonist Oral Anticoagulants Considerations On Once- Vs. Twice-daily Regimens No clinical data available for NOACs to show the effect on the outcome when a twice-daily dose is skipped vs a once-daily dose

28 Novel Oral Anticoagulants NOACs all provide important advantage over W, including convenience, at least as effective prevention of stroke, and less intracranial hemorrhage Growing clinical practice data, despite differences in selection, treatment and management of pts, support the efficacy and safety profile of NOACs Until head-to-head trials in specific settings are available, indirect comparison are just one tool for hypothesis generating Differences in PK/PD caracteristics of each drug allow the tayloring of the most appropriate therapy in a single setting

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30 Thromboembolism and Bleeding

31 Safety and Efficacy of Dabi in Clinical Practice Data From Medicare RE-LY > pts Medicare > pts accessed on August 2014

32 NOACs GI Bleeding Outcome vs Warfarin RE-LY Dabigatran 150 mg BID ROCKET-AF Rivaroxaban 20 mg OD ARISTOTLE Apixaban 5 mg BID ENGAGE-AF Edoxaban 60 mg OD HR HR HR HR (95% CI) (95% CI) (95% CI) (95% CI) GI Bleeding 1.50 ( ) 1.39 ( ) 0.89 ( ) 1.23 ( )

33 Le Definizioni Di Sanguinamenti Maggiori Sono Differenti Tra I Diversi Studi 1 Patel, M. et al., 2011, 2 Connolly et al., 2009, 3 Guigliano et al. 2013, 4 Granger, C. et al., 2011, 5 Connolly, S. et al., 2011

34 GI Bleeding and Edoxaban Warfarin * Edoxaban 60/30 mg Major GI bleeding Upper GI bleed Lower GI bleed Fatal GI bleed Life-threatening bleed *Edoxaban vs warfarin: RR 1.23 (95% CI, ); p=0.033 Edoxaban Warfarin 60/30 mg Life Threatening or fatal GI bleeding Aisenberg et al. Circulation 2015; 132: A17392

35 Major Bleeding in Patients With NV-AF Pharmacovigilance Study of Pts Taking Rivaroxaban From Jan 2013, to Mar 2014, US- DoD electronic HC records 496 MB events in 478 pts, incidence of 2.86 per 100 person-yrs MB was most commonly GI (88.5%) or ICl (7.5%) 46.7% of MB pts received a transfusion, none any type of clotting factor 14 pts died during their MB hospitalization, fatal bleeding incidence rate of 0.08 per 100 pts/y Tamayo S. Clin. Cardiol. 2015; 38: 63-68

36 Giugliano RP. American Journal of Medicine 2016; 129, modif

37 Comparing NOACs And Warfarin in Elderly Pts Risk Of Major Bleeding ,1 3 2,72,8 2,8 2 2,5 3,3 5,1 4,9 4,4 4,4 3,3 5,2 4 4,8 WA 1 0 Age < 75 years Age > 75 years

38 Efficacy and Safety of Rivaroxaban Among Elderly Ps With NVAF Data From ROCKET-AF Trial Halperin JL. Circulation. 2014;130: