la forza sociale e culturale delle evidenze scientifiche
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la forza sociale e culturale delle evidenze scientifiche
Utilizzo dei NAO nella FA non valvolare: la forza sociale e culturale delle evidenze scientifiche Paolo Colonna, MD FESC Cardiologia Ospedaliera, Policlinico di Bari Presidente eletto nazionale SIEC New oral anticoagul in AF Position del WG thrombosis ESC De Caterina, G It Card 2012 Efficacia: ictus o embolia sist Guest editor: Paolo Colonna Sicurezza: emorragie maggiori Efficacy and safety of dabigatran etexilate and warfarin in ‘real world’ patients with AF: A prospective nationwide cohort study Larsen T, et al. JACC 2013 Efficacy and safety of dabigatran etexilate and warfarin in ‘real world’ patients with AF: A prospective nationwide cohort study Larsen T, et al. JACC 2013 Efficacy and safety of dabigatran etexilate and warfarin in ‘real world’ patients with atrial fibrillation: A prospective nationwide cohort study. Larsen T, et al. JACC 2013 Risultati dall’esperienza nella pratica clinica - Food and Drug Administration Cardiovascular, bleeding, and mortality risks in elderly medicare patients treated with dabigatran or warfarin for non-valvular AF Graham et al. Circ 2014 in press Cardiovascular, bleeding, and mortality risks in elderly medicare patients treated with dabigatran or warfarin for non-valvular AF Graham et al. Circ 2014 in press Cardiovascular, bleeding, and mortality risks in elderly medicare patients treated with dabigatran or warfarin for non-valvular AF Graham et al. Circ 2014 in press Cardiovascular, bleeding, and mortality risks in elderly medicare patients treated with dabigatran or warfarin for non-valvular AF Graham et al. Circ 2014 in press Cardiovascular, bleeding, and mortality risks in elderly medicare patients treated with dabigatran or warfarin for non-valvular AF Graham et al. Circ 2014 in press • • • • • ischemic stroke: 0.80 (0.67-0.96); intracranial hemorrhage: 0.34 (0.26-0.46); major gastrointestinal bleeding: 1.28 (1.14-1.44); acute myocardial infarction: 0.92 (0.78-1.08); death: 0.86 (0.77-0.96). In subgroup with dabigatran 75 mgX2, no difference in risk except ↓ intracranial hemorrhage Cardiovascular, bleeding, and mortality risks in elderly medicare patients treated with dabigatran or warfarin for non-valvular AF RE-LY®2-5 Medicare1 Graham et al. Circ 2014 in press HR: 0.97 P=0.50 HR: 0.86 P=0.006 HR: 1.28 P<0.001 HR: 0.80 P=0.02 HR: 0.92 P=0.29 HR: 0.34 P<0.001 RR: 0.88 P=0.05 RR: 0.94 P=0.41 HR: 0.76 P=0.03 RR: 0.41 P<0.001 RR: 1.48 P=0.001 RR: 1.27 P=0.12 Warfarin... è arrivato il momento di rottamarlo? NOA warfarin Update sui NAO: Analisi di Efficacia • • • • • • • • • Già in anticoagulazione / naive Solo nel PT INR mal controllato (basso TTR) Parossistica o permanente Nel basso CHADSVasc o HASBLED Nel pregresso ictus Nello scompenso In cardioversione elettrica Nelle valvulopatie / protesi biologiche In CP ischemica e terapia con ASA ROCKET AF – primary efficacy endpoint subgroup analysis Rivaroxaban n/N Overall Hazard ratio and 95% CIs Warfarin (%) n/N p(%) value* 189/7,061 2.7 243/7,082 3.4 Previous ASA use 0.94 Yes 70/2,567 2.7 91/2,606 3.5 No 119/4,494 2.7 152/4,476 3.4 Previous VKA use 0.42 Yes Experienced 114/4,401 2.6 140/4,437 3.2 No Naive 75/2,660 2.8 103/2,645 3.9 AF type 0.30 Persistent 159/5,739 2.8 206/5,723 3.6 Paroxysmal 28/1,228 2.3 30/1,259 2.4 2/94 2.1 7/100 7.0 Newly diagnosed *p-value for interaction. Safety population – on-treatment analysis. Patel MR et al, 2011. 0.1 0.2 0.5 Favours rivaroxaban 1 2 5 10 Favours warfarin 15 Update sui NAO: Analisi di Efficacia • • • • • • • • • Già in anticoagulazione / naive Solo nel PT INR mal controllato (basso TTR) Parossistica o permanente Nel basso CHADSVasc o HASBLED Nel pregresso ictus Nello scompenso In cardioversione elettrica Nelle valvulopatie / protesi biologiche In CP ischemica e terapia con ASA Comparison of Trial Metrics RE-LY Time in Therapeutic Range (TTR) 64% 67% warfarinexperienced 61% warfarinnaïve Rocket AF Aristotle Mean 55% Mean 62% Median 58% Median 66% EngageAF Mean 65% Median 68% Efficacy and TTR in 3 SPAF studies FDA Commettee Meeting, 8 sept 2011 Update sui NAO: Analisi di Efficacia • • • • • • • • • Già in anticoagulazione / naive Solo nel PT INR mal controllato (basso TTR) Parossistica o permanente Nel basso CHADSVasc o HASBLED Nel pregresso ictus Nello scompenso In cardioversione elettrica Nelle valvulopatie / protesi biologiche In CP ischemica e terapia con ASA Type of AF subanalysis: stroke/systemic embolism Flaker et al. J Am Coll Cardiol ‘12 Dabigatran 110 Dabigatran 150 Type of AF Paroxysmal Persistent Permanent RE-LY total 0.1 1 Hazard ratio 0.1 10 1 10 Hazard ratio April 2012 Efficacy and Safety of Rivaroxaban Compared to Warfarin in Patients With Paroxysmal, Persistent, and Newly Diagnosed AF: The ROCKET-AF Study Patel MR et al. N Engl J Med 2011 Update sui NAO: Analisi di Efficacia • • • • • • • • • Già in anticoagulazione / naive Solo nel PT INR mal controllato (basso TTR) Parossistica o permanente Nel basso CHADSVasc o HASBLED Nel pregresso ictus Nello scompenso In cardioversione elettrica Nelle valvulopatie / protesi biologiche In CP ischemica e terapia con ASA Sottoanalisi ReLY per punteggio CHADS2: ictus ed embolia sistemica Oldgren J et al. Ann Int Med 2011 Yearly rate (%) Dabigatran 110 BID vs. warfarin D 110 mg BID D 150 mg BID Warfarin 0–1 1.06 0.65 1.08 2 1.45 0.84 1.38 3–6 2.12 1.88 2.73 CHADS2 Score P=0.44 Dabigatran 150 BID vs. warfarin P=0.82 0.5 1.0 0.5 1.0 1.5 2.0 0 0 Better Better Better Warfarin Dabigatran Dabigatran 1.5 2.0 Better Warfari n 2/3 1/2 1/2 NAO in elderly pts. Colonna Cardiolink 2014 Sanguinam Anni Ictus maggiori HR meglio NAO Emorragie intracraniche HR HR meglio warfarin meglio NAO meglio warfarin meglio NAO meglio warfarin 6076 6015 6022 150mg BID 110mg BID W randomizz 1:1 cieca ai due dosaggi 5619 20mg OD insuff renale moderata (ClCr 30-49 ml) 1462 15mg OD 7081 W 8692 5mg BID 428 2.5mg BID 9081 W 60mg OD 30mg OD W 7035 7034 7036 2 fra: -età ≥ 80, -peso<60 kg, -Cr ≥1.5 mg/dl randomizz 1:1 cieca + ClCr 30-49 ml o peso<60 kg o “farmaci” durante lo studio Update sui NAO: Analisi di Efficacia • • • • • • • • • Già in anticoagulazione / naive Solo nel PT INR mal controllato (basso TTR) Parossistica o permanente Nel basso CHADSVasc o HASBLED Nel pregresso ictus Nello scompenso In cardioversione elettrica Nelle valvulopatie / protesi biologiche In CP ischemica e terapia con ASA Dabigatran compared with warfarin in AF and previous TIA or stroke: a subgroup analysis of the RE-LY trial Diener G, Lancet Neurol 2010 Time to stroke or SSE in pts with stroke Update sui NAO: Analisi di Efficacia • • • • • • • • • Già in anticoagulazione / naive Solo nel PT INR mal controllato (basso TTR) Parossistica o permanente Nel basso CHADSVasc o HASBLED Nel pregresso ictus Nello scompenso In cardioversione elettrica Nelle valvulopatie / protesi biologiche In CP ischemica e terapia con ASA Efficacy and safety of rivaroxaban in patients with heart failure and AF: insights from ROCKET AF Van Diepen et al. Circ H F 2013 Analysis of 1.270 pts undergoing cardioversion (in ReLY trial) Nagarakanti, Circ 2011 Stroke / embolism at 30 days Rocket-AF 285 pts (JACC ‘13) 5 4,5 4 3,5 3 2,5 2 1,5 1 0,5 0 Aristotle 570 pts (Abs Esc ‘12) p = n.s. Warfarin D110 mg D110 mg D150 Warfarin mg D150 mg TOE prior cardioversion NO TOE prior cardioversion Rationale and design of the X-Vert trial in pts scheduled for cardioversion Cappato R Eur Heart J 2014: online only X-VeRT: time to cardioversion by cardioversion strategy Cappato R Eur Heart J 2014: online only Median time to cardioversion Rivaroxaban VKA Days 80 p<0.001 60 p=0.628 40 22 days 20 30 days p<0.001 Patients (%) 100 Patients cardioverted as scheduled* 1 patient with inadequate anticoagulation 95 patients with inadequate anticoagulation 0 Early Delayed Delayed cardioversion Not performed cardioversion as first scheduled from 21–25 days primarily due to inadequate anticoagulation (indicated by drug compliance <80% for rivaroxaban or weekly INRs outside the range of 2.0–3.0 for 3 consecutive weeks before cardioversion for VKA) Update sui NAO: Analisi di Efficacia • • • • • • • • • Già in anticoagulazione / naive Solo nel PT INR mal controllato (basso TTR) Parossistica o permanente Nel basso CHADSVasc o HASBLED Nel pregresso ictus Nello scompenso In cardioversione elettrica Nelle valvulopatie / protesi biologiche In CP ischemica Esclusione di FA “valvolare” Re-LY Rocket-AF Aristotle Engage AF Dabigatran Rivaroxaban Apixaban Edoxaban Protesi meccanica Stenosi mitralica mod-severa VP severa da operare (sang) Protesi biologica E E E E E E E E E E Riparazione valvolare (+anello/plast) I I I I I Tot trials Re-LY Rocket AF Aristotle Ezekowitz MD et al. ACC 2014 Abs Breithardt G et al. EHJ 2014 online Avezum A et al. ESC 2013 Abs 18.113 14.171 18.201 Tot SVD 3.950 21,8% 2.003 14,1% 4.808 26,4% MR 3.101 78,5% 1.756 87,7% 3.526 73,3% AR 817 20,7% 486 24,3% 887 18,4% AS 471 11,9% 215 10,7% 384 8,0% TR 1.179 29,8% 2.124 44,2% 193 4,9% 131 2,7% mild MS prior valve procedures 106 5,3% 251 5,2% SVD: considerata significativa dal medico che arruolava per i riflessi sulla pratica clinica Clinical characteristics and outcomes in AF and native mitral and aortic valve disease in the ROCKET AF trial Breithardt G et al. EHJ 2014 online Efficacy: Stroke or systemic embolism I NAO nei pazienti senza valvulopatia e con valvulopatia lieve-moderata • Valvulopatia moderata + severa (esclusa SM) senza intervento pianificato • • • Protesi valvolare biologica Pregressa plastica valvolare + anello TAVI o mitral clip • • • Protesi valvolare meccanica Stenosi mitralica severa Valvulopatia con intervento CCH pianificato Concomitant Use of Antiplatelet Therapy with Dabigatran or Warfarin Dans M et al. Circulation 2013 62% 38% 32+2% 4% 6.952 (38.4%) received concomitant aspirin or clopidogrel, or both 6.3 5.5 Rate of Major Bleeding (% per year) 4.8 4.6 4.4 5.4 * 4.3 3.9 2.8 2.6 2.2 3.8 Management of antithrombotic therapy in AF pts with ACS and/or undergoing PTCA Recommendations of ESC, EHRA, EAPCI Lip G et al. EurHeartJ 2014 Management of antithrombotic therapy in AF pts with ACS and/or undergoing PTCA Recommendations of ESC, EHRA, EAPCI Lip G et al. EurHeartJ 2014 NAO vecchi e nuovi farmaci: differenze, luci e ombre • Randomizzazione dosaggi • Mono – bisomministrazione giornaliera • Comportamento per ↓ funzione renale • Efficacia sull’ictus ischemico • Rischio di sanguinamento • Dati nella cardioversione elettrica • Controindicati in: protesi valvolari meccaniche • Insuff renale severa • Neoplasie attive, insuff epatica severa