I nuovi anticoagulanti orali nella trombosi venosa profonda. Terapia della TVP. Fulvio POMERO. Medicina Interna S. Croce e Carle Cuneo

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1 I nuovi anticoagulanti orali nella trombosi venosa profonda Terapia della TVP Fulvio POMERO Medicina Interna S. Croce e Carle Cuneo

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4 Poor VKA control (first 90 days) Good VKA control (first 90 days) Cumulative incidence of recurrence after oral anticoagulation interruption in subjects with a previous unprovoked venous thromboembolic Palareti G et al. JTH 2005; 3:

5 Palareti G et al. Lancet 1996; 348:

6 National cross-sectional survey 2,633 patients were included Mean age was 87.2 ± 4.4 years Mean (±SD) TTR was 57.9 ± 40.4 %. Poor VKA control (TTR < 50% vs > 50%) was associated with: OR 95 % CI History of INR > Recent VKA prescription (<1 vs. >12 months) Hospitalization vs. nursing home History of major bleeding Falls ( 2 falls during the past year vs. <2) Antibiotic use Plichart M et al. Drugs Aging 2013; Oct 30. [Epub ahead of print]

7 x x Beccattini C et al. Thromb Res 2012; 129:

8 Beccattini C et al. Thromb Res 2012; 129:

9 RECOVER NEJM 2009; 361: HOKUSAY NEJM 2013; 369:

10 Efficacy outcome Recurrent VTE Event rate DABIGATRAN 2.4 % WARFARIN 2.1 % RECOVER HR= 1.10 (95% CI= ) P<0.001 for noninferiority NEJM 2009; 361: Efficacy outcome Recurrent VTE Event rate EDOXABAN 3.2 % WARFARIN 3.5 % HOKUSAY HR= 0.89 (95% CI= ) P<0.001 for noninferiority NEJM 2013; 369:

11 RECOVER RR 71% P < Safety outcome Major bleeding / any bleeding P=0.38 NEJM 2009; 361: HOKUSAY Safety outcome Major + Clinically Relevant non Major Bleeding Event rate EDOXABAN 8.5 % WARFARIN 10.3 % P = for superiority HR= 0.81 (95% CI= ) NEJM 2013; 369:

12 Beccattini C et al. Thromb Res 2012; 129:

13 Osservazione di 30 giorni TVP confermata senza EP sintomatica N 3449 RIVAROXABAN RIVAROXABAN EP confermata con o senza TVP sintomatica R N mg bid 20 mg od gg 21 Periodo di trattamento predefinito ( mesi) Enoxaparina 1 mg/kg bid per almeno 5 gg + VKA (INR 2-3) EINSTEIN investigators NEJM 2010; 363:

14 THRIVE study (Ximelagatran) Efficacy outcome Recurrent VTE Fiessinger J-N et al. JAMA 2005;293: van Gogh PE study (Idraparinux) Efficacy outcome Recurrent VTE The van Gogh Investigators. N Engl J Med 2007;357:

15 Efficacy outcome Recurrent venous thromboembolism p< for non inferiority Event rate RIVAROXABAN 2.1 % Enox- WARFARIN 3.0 % HR= 0.68 (95% CI= ) EINSTEIN investigators NEJM 2010; 363:

16 Safety outcome Major bleeding or clinically relevant nonmajor bleeding P= 0.77 Event rate RIVAROXABAN 8.1 % Enox- WARFARIN 8.1 % Event rate RIVAROXABAN 0.8 % Major bleeding HR= 0.65 (95% CI= ) Enox-WARFARIN 1.2 % EINSTEIN investigators NEJM 2010; 363:

17 Osservazione di 30 giorni AMPLIFY APIXABAN gg 7 APIXABAN TEV N 5395 R 10 mg bid 5 mg bid Periodo di trattamento predefinito (6 mesi) Enoxaparina 1 mg/kg bid per almeno 5 gg + VKA (INR 2-3) Agnelli G et al. NEJM 2013; 369:

18 AMPLIFY Efficacy outcome Recurrent venous thromboembolism Event rate APIXABAN 2.3 % Enox- WARFARIN 2.7 % HR= 0.84 (95% CI= ) Agnelli G et al. NEJM 2013; 369:

19 AMPLIFY Major Bleeding HR= 0.31 (95% CI= ) Event rate APIXABAN 0.6 % Enox- WARFARIN 1.8 % Agnelli G et al. NEJM 2013; 369:

20 Osservazione di 30 giorni POOLED ANALYSIS TVP confermata senza EP sintomatica N 3449 RIVAROXABAN RIVAROXABAN EP confermata con o senza TVP sintomatica R N mg bid 20 mg od gg 21 Periodo di trattamento predefinito ( mesi) Enoxaparina 1 mg/kg bid per almeno 5 gg + VKA (INR 2-3) EINSTEIN investigators NEJM 2010; 363:

21 8282 patients HR=0.89 ; 95% CI Primary efficacy outcome p non inferiority < Event rate RIVAROXABAN 2.1 % Enox- WARFARIN 2.3 % HR=0.93 ; 95% CI Principal safety outcome p = 0.27 Event rate RIVAROXABAN 9.4 % Enox- WARFARIN 10 % Prins MH et al. Thrombosis Journal 2013; 11: 21-31

22 8282 patients Event rate RIVAROXABAN 1.0 % Enox- WARFARIN 1.7 % Major bleeding HR=0.54; 95% CI p = Prins MH et al. Thrombosis Journal 2013; 11: 21-31

23 8282 patients Efficacy outcomes in fragile patients and subgroups Prins MH et al. Thrombosis Journal 2013; 11: 21-31

24 8282 patients Safety outcomes in fragile patients and subgroups Prins MH et al. Thrombosis Journal 2013; 11: 21-31

25 Beccattini C et al. Thromb Res 2012; 129:

26 3 mesi vs 12 mesi Agnelli G et al. NEJM 2001; 345: 165-9

27 Kearon K et al. JTH 2007; 5:

28 Osservazione di 30 giorni Periodo di trattamento predefinito (12 mesi) TVP confermata che abbia completato i 6-12 mesi di rivaroxaban o VKA N 1197 R RIVAROXABAN 20 mg od Placebo EINSTEIN investigators NEJM 2010; 363:

29 Symptomatic Recurrent VTE Event rate RIVAROXABAN 1.3 % PLACEBO 7.1 % HR= 0.18 (95% CI= ) p< for superiority EINSTEIN investigators NEJM 2010; 363:

30 Safety outcome Event rate Major or clinically relevant non major Major bleeding RIVAROXABAN 6.0 % p < p = 0.11 Placebo 1.2 % 0 EINSTEIN investigators NEJM 2010; 363:

31 Recurrent symptomatic VTE and VTE-related deaths Sardar P et al. Drugs 2013; 73:

32 All-cause mortality Sardar P et al. Drugs 2013; 73:

33 Major bleeding Sardar P et al. Drugs 2013; 73:

34 Major or Clinically Relevant Nonmajor Bleeding Sardar P et al. Drugs 2013; 73:

35 - Agnelli G et al. Best Practice & Research Clinical Haematology 2013; 26:

36 I nuovi anticoagulanti orali nella trombosi venosa profonda Terapia della TVP Fulvio POMERO Medicina Interna S. Croce e Carle Cuneo