I Nuovi anticoagulanti orali Domenico Prisco DMSC Università di Firenze SOD Medicina Interna Interdisciplinare AOU Careggi Firenze Pistoia 23 gennaio 2016

Anticoagulanti e coagulazione inibitori indiretti: fondaparinux LMWH antagonisti vitamina K: warfarin acenocumarolo inibitori diretti: rivaroxaban apixaban betrixaban edoxaban dabigatran argatroban ximelagatran hirudin, bivalirudin

Prisco D, J Cardiovasc Med 2015

Vantaggi dei NAO Effetto anticoagulante NON necessario Rapido effetto terapeutico Non necessario “bridging” Target su specifico enzima coagulazione Basso rischio di eventi avversi Bassa interferenza con i cibi No restrizioni dietetiche Basse interazioni con farmaci Meno restrizioni farmacologiche Effetto anticoagulante NON necessario prevedibile monitoraggio di laboratorio

Drug-Drug Interactions and Dose Adjustments With NOACs

I risultati nei trial sulla FA

Burden of Atrial Fibrillation E’ tempo per uno screening (opportunistico ) della FA?

Stroke or systemic embolic events Dabigatran 150 mg bid Rivaroxaban 20 mg od Apixaban 5 mg bid Edoxaban 60 mg od Ruff C, Lancet 2013

Secondary efficacy and safety outcomes Dabigatran 150 mg bid Rivaroxaban 20 mg od Apixaban 5 mg bid Edoxaban 60 mg od Ruff C, Lancet 2013

Major bleeding Dabigatran 150 mg bid Rivaroxaban 20 mg od Apixaban 5 mg bid Edoxaban 60 mg od Ruff C, Lancet 2013

Stroke or systemic embolic events subgroups Ruff C, Lancet 2013

Major bleeding subgroups Ruff C, Lancet 2013

La stratificazione del rischio

CHA2DS2VASc NB La maggior parte dei pazienti in validation cohort sono a CHADS2 da 2 in su!!! Inoltre molti sotto warfarin

HAS-BLED bleeding risk score REAL WORLD 3978 soggetti europei con FA SCORE >3 alto rischioBased on 3,978 patients in the Euro Heart Survey on AF with complete follow-up, all univariate bleeding risk factors in this cohort were used in a multivariate analysis along with historical bleeding risk factors. A new bleeding risk score termed HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly ( . 65 years), Drugs/alcohol concomitantly) was calculated, incorporating risk factors from the derivation cohort. Results: Fifty-three (1.5%) major bleeds occurred during 1-year follow-up. The annual bleeding rate increased with increasing risk factors. The predictive accuracy in the overall population using signifi cant risk factors in the derivation cohort (C statistic 0.72) was consistent when applied in several subgroups. Application of the new bleeding risk score (HAS-BLED) gave similar C statistics except where patients were receiving antiplatelet agents alone or no antithrombotic therapy, with C statistics of 0.91 and 0.85, respectively. Conclusion: This simple, novel bleeding risk score (HAS- > 3 high risk: attentionbothwith ASA and OAT Pisters The Euro HeartSurvey. Chest 2010

Necessità di terapia antiaggregante

National Swedish Patient register, matched with data from the National Prescribed Drugs register

Concomitant Use of Antiplatelet Therapy with Dabigatran or Warfarin in the RELY Trial Dans Al et al, Circulation 2013

Dabigatran 110mg might be a safer alternative to warfarin in patients requiring antiplatelet therapy Post hoc analysis: use of antiplatelet therapy was not randomized or stratified. Antiplatelet therapy left at the discretion of the physician. Most patients were taking ASA (80mg or more), 1,9% Clopidogrel, 4,5% DAPT (median duration, 66% of the study period). Adding a single anti-platelet drug increased the risk of major bleeding by 60%.

Clinical contexts from which evidence regarding triple therapy of OAC, aspirin and clopidogrel is derived Rubboli A , TR 2015

Thromb Haemost 2014

Thromb Haemost 2014

2014 ESC/EACTS Guidelines on myocardial revascularization The dose intensity of oral anticoagulation should be carefully monitored with a target INR of 2.0–2.5 in the case of vitamin K antagonists and use of lower tested dose for stroke prevention in the case of NOACs (dabigatran 110 mg b.i.d.; rivaroxaban 15 mg once daily, apixaban 2.5 mg).

Clinical contexts from which evidence regarding triple therapy of OAC, aspirin and clopidogrel is derived Rubboli A , TR 2015

Suggested algorithm for the selection of OAC, and dose, to be combined with DAPT in patients recently submitted to PCI-S who develop AF Rubboli A , TR 2015

Future trials evaluating the optimal antithrombotic regimen in patients undergoing percutaneous coronary intervention with stent implantation on chronic oral anticoagulation Jagrohe D, Curr Opin Cardiol 2015

La terapia del TEV

Acute and chronic treatment of VTE with NOAs Phase III trials Drug/Trial Clinical Condition DABIGATRAN RE-COVER studies Treatment of acute VTE RE-MEDY and RE-SONATE studies Secondary prevention of VTE RIVAROXABAN EINSTEIN program Treatment of acute DVT Treatment of acute PE APIXABAN AMPLIFY program EDOXABAN HOKUSAI study Acute and long term treatment of VTE

First VTE or VTE-related death

Major bleedings

Major bleedings (2)

La profilassi del TEV

VALUTAZIONE DEL RISCHIO TROMBOEMBOLICO INDIVIDUALE A RISCHIO DOVUTO ALL’ EVENTO B RISCHIO DOVUTO A FATTORI PERSONALI PREDISPONENTI A+B RISCHIO GLOBALE VALUTARE RISCHIO EMORRAGICO

NAO e profilassi del TEV nel paziente internistico Trial di fase III DOAC, dosaggio e durata Farmaco comparato, dosaggio e durata Principali risultati MAGELLAN Rivaroxaban 10 mg x 35 giorni Enoxaparina 40 mg x 10 giorni ↔ efficacia a 10 giorni, ↑ efficacia a 35 giorni ↓sicurezza a 10 giorni, ↓ sicurezza a 35 giorni ↓ beneficio clinico netto ADOPT Apixaban 2,5 mg x 2 x 30 giorni Enoxaparina 40 mg x 6-14 giorni ↔ efficacia a 30 giorni ↓ sicurezza a 30 giorni APEX Betrixaban Enoxaparina IN CORSO

ADOPT and MAGELLAN: main results Imberti D , Intern Emerg Med 2013

Results of a meta-analysis of ADOPT and MAGELLAN studies Imberti D , Intern Emerg Med 2013

Conclusion The evidence of this analysis confirms that in acute medically ill patients, prolonged thromboprophylaxis with an oral FXa inhibitor is more protective than regular short-term treatment with enoxaparin, even if the results of only one study (MAGELLAN) could have influenced those of the meta-analysis itself. However, treatment with FXa inhibitors is associated with significant major bleeding, both in long- and short-term treatment compared with enoxaparin Imberti D , Intern Emerg Med 2013

Conclusion Physicians guidelines recommend short-term parenteral anticoagulant prophylaxis with UFH, LMWH or fondaparinux for all high-risk medical patients during hospitalization. The results of the MAGELLAN and ADOPT studies should not change our daily clinical practice of VTE prophylaxis in medical patients and, at least at the moment, new OACs should not be recommended in this clinical setting. Imberti D , Intern Emerg Med 2013

ACCP recommendations Initiate low-dose unfractionated heparin two or three times daily, low molecular- weight heparin (LMWH), or fondaparinux in acutely ill hospitalized medical patients with an increased risk of thrombosis (grade: 1B). Avoid chemical prophylaxis in acutely ill hospitalized patients at low risk of thrombosis (grade: 1B). Avoid chemical prophylaxis in acutely ill hospitalized patients who are bleeding or have a high risk of bleeding (grade: 1B). Initiate mechanical prophylaxis with graduated compression stockings or intermittent pneumatic compression in acutely ill hospitalized patients who have compelling risk factors for both thrombosis and major bleeding or are currently bleeding (grade: 2C). Kahn SR, Chest 2012

Le indicazioni delle linee guida della regione toscana

I mezzi di Profilassi Raccomandazioni • Le CCG sono indicate per la profilassi dei pazienti chirurgici con controindicazione assoluta a profilassi farmacologica per alto rischio emorragico (prova I A). • Nei pazienti chirurgici le CCG possono essere utilizzate in combinazione con la profilassi farmacologica allo scopo di ridurre l’incidenza di TVP (prova I A). • L’uso delle CCG potrebbe essere considerato nei pazienti ad altissimo rischio di TVP ricoverati in terapia intensiva in associazione alla profilassi farmacologica (prova VI B). LG Regione Toscana

I mezzi di Profilassi Raccomandazione La CPI è indicata nella profilassi della TVP nei pazienti chirurgici e in quelli ricoverati in terapia intensiva (prova I A). La CPI è indicata nei pazienti con ictus emorragico in fase acuta (prova IIA) e nei pazienti con ictus ischemico ad alto rischio di trasformazione emorragica (prova VI A) LG Regione Toscana

I pazienti con insufficienza renale L’uso di fondaparinux e dabigatran è assolutamente controindicato per clearance della creatinina rispettivamente <20 e <30 ml/min rispettivamente, in base alla scheda tecnica. L’uso di apixaban e rivaroxaban è controindicato per clearance della creatinina < 15 ml/min. Nei pazienti con clearance fra 20 e 50 ml/min, la scheda tecnica di fondaparinux consiglia di utilizzare la dose di 1,5 mg/dì. Nei pazienti con clearance della creatinina fra 30 e 50 ml/min la scheda tecnica di dabigatran suggerisce la dose di 75 mg due volte al giorno. LG Regione Toscana

La Profilassi nei pazienti con Insufficienza Renale Nei pazienti con clearance della creatinina <30 ml/min, i livelli plasmatici di rivaroxaban possono aumentare in misura significativa; ciò può aumentare il rischio emorragico. Le schede tecniche controindicano l’uso di apixaban rivaroxaban in pazienti con clearance della creatinina <15 ml/min, mentre suggerisce un uso prudente nei pazienti con clearance della creatinina 15-29 ml/min. Cautela è suggerita anche nei pazienti con insufficienza renale moderata (clearance della creatinina 30-49 ml/min) trattati contemporaneamente con farmaci che inducono un aumento delle concentrazioni plasmatiche di apixaban e rivaroxaban. LG Regione Toscana

La Profilassi nei pazienti con Insufficienza Renale • valutare la funzione renale ogni qual volta si deve decidere sull’uso e/o il dosaggio di EBPM, fondaparinux e altri farmaci antitrombotici che sono eliminati per via renale, soprattutto in pazienti anziani, con diabete mellito e con rischio emorragico elevato (prova I A); • seguire, in rapporto ai diversi quadri clinici, una delle seguenti opzioni: evitare l’uso di anti- coagulanti che si accumulano in presenza di IRC, utilizzare una dose più bassa o monitorare le concentrazioni del farmaco o la sua efficacia terapeutica (prova I B). LG Regione Toscana

Profilassi del tromboembolismo venoso in chirurgia ortopedica LG Regione Toscana

Gestione perioperatoria

The question of whether antithrombotic therapy should be suspended in a patient who will be undergoing an invasive procedure involves balancing the risk of postprocedural bleeding with continued treatment against the thrombotic risk with suspension of treatment and use of bridging anticoagulation therapy

Invasive procedures where the bleeding risk is low and oral anticoagulation can often be continued Patel J, Br J of Hematol 2013

Classification of surgical interventions according to bleeding risk LG EHRA ESC 2013

ACCP risk stratification of patients treated with oral anticoagulant (Douketis, 2012) Patel J, Br J of Hematol 2013

Guidelines applied at King’s College Hospital for oral VKA therapy Patel J, Br J of Hematol 2013

Bridging Therapy Siegal D, Circulation 2012

Forest plot of thromboembolic events Siegal D, Circulation 2012

Forest plot of Forest plot of overall bleeding events Siegal D, Circulation 2012

Forest plot of Forest plot of major bleeding events Siegal D, Circulation 2012

Conclusion We found that VKA-treated patients who require an elective surgical or invasive procedure and receive periprocedural bridging anticoagulation with LMWH appear to be at increased risk of overall and major bleeding and at similar risk of thromboembolic events compared with non bridged patients. The ACCP and other antithrombotic guidelines advocate that bridging anticoagulation should be undertaken with consideration of individual patient thromboembolic risk and procedural bleeding risk by balancing expected benefits and harms. Siegal D, Circulation 2012

Douketis J, NEJM 2013

Douketis J, NEJM 2015

Study Outcome Douketis J, NEJM 2015

Conclusion In the BRIDGE trial, we found that for patients with atrial fibrillation who require temporary interruption of warfarin treatment for an elective operation or other elective invasive procedure, a strategy of forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism. The strategy of forgoing bridging treatment also decreased the risk of major bleeding Douketis J, NEJM 2015

Pengo V, TH 2009

High thromboembolic risk: mechanical mitral valve prostheses, monoleaflet mechanical aortic prostheses or bileaflet aortic prostheses associated with AF or previous arterial embolism, AF associated with previous arterial thromboembolism or mitral valve disease, previous cardiogenic or unexplained systemic embolism, and venous thromboembolism in the previous 3 months. All other cases were considered low to intermediate thromboembolic risk. Another step is the measurement of the anti-hemostatic effect of the anti- Thrombotic agents, if possible. This allows to ascertain that bleeding is related To the drug effect and that reversal is indicated.

Anticoagulation Protocols Applied According to Patient Thromboembolic Risk Pengo V, TH 2009

Study Flow-Chart Pengo V, TH 2009

Thromboembolic Event Details Pengo V, TH 2009

Conclusion The incidence of thromboembolic events was low. All 5 thromboembolic events occurred in high thromboembolic- risk patients resulting in an incidence 1.7%. We also found a low incidence of bleeding events (major bleeding, 1.2%). Pengo V, TH 2009

NOAC Discontinuation Prior to Elective Surgical Intervention

Approved European labels for NOACs and their dosing in CKD Heidbuchel H, Europace 2015

Profilassi nei pazienti che hanno sospeso gli anticoagulanti orali inibitori della vitamina K Alto rischio -> EBPM 70 U/kg x 2 Basso e medio rischio -> EBPM alla dose profilattica elevata LG Regione Toscana

BRIDGING Therapy in pazienti sotto inibitori della vitamina K LG Regione Toscana

Gestione dei pazienti in terapia con NAO da sottoporre a chirurgia d’elezione LG Regione Toscana

Gestione dei pazienti in terapia con NAO da sottoporre a chirurgia d’elezione LG Regione Toscana

La gestione delle emergenze: antidoti

Strategies for anticoagulation reversal in bleeding associated with warfarin and new oral anticoagulants Enriquez A, Europace 2015

Management of bleeding associated with NOACs Enriquez A, Europace 2015

Comparison of specific antidotes for NOACs Enriquez A, Europace 2015

DOAC-Antidotes Pollack V, NEJM 2015

Time Courses of Plasma Concentrations of Unbound Dabigatran DOAC-Antidotes Time Courses of Plasma Concentrations of Unbound Dabigatran before and after the Administration of Idarucizumab patients who had serious bleeding patients who required urgent surgery Pollack V, NEJM 2015

Time Courses of Plasma Concentrations of Idarucizumab before and after the Administration of Idarucizumab patients who had serious bleeding patients who required urgent surgery Pollack V, NEJM 2015

Idarucizumab for dabigatran reversal DOAC-Antidotes Idarucizumab for dabigatran reversal Rapidly and complete reversal of the anticoagulant activity of dabigatran in 88 to 98% of patients No safety concerns among the 90 patients involved in this study — including patients who were given idarucizumab on clinical grounds but were later found to have had normal results on clotting tests at baseline — or among the more than 200 volunteers who were administered idarucizumab in previous studies Pollack V, NEJM 2015

DOAC-Antidotes

Siegal D, NEJM 2015

Time Courses of Anti–Factor Xa Activity before and after Administration of Andexanet Siegal D, NEJM 2015

Time Courses of Anti–Factor Xa Activity before and after Administration of Andexanet Siegal D, NEJM 2015

Time Courses of Plasma Concentrations of Unbound Apixaban or Rivaroxaban before and after Administration of Andexanet Siegal D, NEJM 2015

Conclusion Andexanet is a specific, rapidly acting antidote that is being developed for urgent reversal of factor Xa inhibitor anticoagulant activity. Siegal D, NEJM 2015

Conclusion In our studies, andexanet rapidly restored factor Xa activity and thrombin generation and reduced unbound factor Xa inhibitor concentrations in apixaban-treated and rivaroxaban-treated older participants. The reversal of anticoagulation with andexanet was not associated with safety concerns or thrombotic events. The ongoing ANNEXA-4 phase 3b–4 study (ClinicalTrials.gov number, NCT02329327) is evaluating the efficacy and safety of andexanet in patients with factor Xa inhibitor–associated acute major bleeding Siegal D, NEJM 2015

In life-threatening situations, the possibility to barely DOAC-Antidotes In life-threatening situations, the possibility to barely immediately reverse the anticoagulation effect of NOACs could have importance. For example, when hemodynamic stability has been compromised during hemorrhagic shock, stopping active bleeding could be necessary in trying to stabilize vital functions. Proietti M, JTT 2015

Quale rapporto costo/efficacia? DOAC-Antidotes Dubbi sugli antidoti La loro efficacia/sicurezza sarà valutata in RCT di adeguata potenza e con sample size decisi su end-point clinici (e non solo farmacologici)? Quale l’appropriatezza del loro uso? Quali i possibili effetti indesiderati? Quale rapporto costo/efficacia?

La ripresa della terapia nei pazienti con NAO

Resumption of antithrombotic therapy Baron T, NEJM 2013

Resumption of anticoagulant based on the peak effect and onset of action Benzon HT, British Journal of Anesthesia 2013

When to restart the non-vitamin K antagonist anticoagulants? For procedures with immediate and complete haemostasis, the NOAC can be resumed 6–8 h after the intervention. The same applies after atraumatic spinal/epidural anaesthesia or clean lumbar puncture (i.e. non-bloody tap). For many surgical interventions, however, resuming full dose anticoagulation within the first 48–72 h after the procedure may carry a bleeding risk that could outweigh the risk of cardio-embolism. Heidbuchel H, Europace 2015

When to restart the non-vitamin K antagonist anticoagulants? For procedures associated with immobilization, it is considered appropriate to initiate a reduced venous thromboprophylactic (e.g. 0.5 mg/kg/day of enoxaparin) or intermediate dose of LMWHs (e.g. 1 mg/kg/day of enoxaparin) 6–8 h after surgery if adequate haemostasis has been achieved, whereas full therapeutic anticoagulation by restarting NOACs is deferred 48–72 h after the invasive procedure Heidbuchel H, Europace 2015

I possibili pazienti su cui riflettere

Which patient subgroups do not from treatment with non-vitamin antagonist oral anticoagulants? benefit K

Dabigatran versus Warfarin in Patients with Mechanical Heart Valves Randomization 2:1 168 DE 84 warfarin Eikelboom J et al NEJM 2013; 369:1206–14

Eikelboom JW et al, N Eng J Med, September 2013 Conclusioni …nessun beneficio ed un eccesso di rischio nei pazienti con protesi valvolari cardiache meccaniche. Unfortunately, dabigatran failed in the treatment of patients with mechanical heart valves. No news of the other direct anticoagulants in these patients. I remember that 10 year ago, a new oral anticoagulant drug, ximelagatran was tested with good results and was promising to replace warfarin. However it was suddenly withdrawn due to potential hepatic toxicity.

Eligibility for NOAC Therapy in AF Patients With Valvular Disease

Apixaban in Comparison With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease CLINICAL PERSPECTIVE by Alvaro Avezum, Renato D. Lopes, Phillip J. Schulte, Fernando Lanas, Bernard J. Gersh, Michael Hanna, Prem Pais, Cetin Erol, Rafael Diaz, M. Cecilia Bahit, Jozef Bartunek, Raffaele De Caterina, Shinya Goto, Witold Ruzyllo, Jun Zhu, Christopher B. Granger, and John H. Alexander Circulation Volume 132(8):624-632 August 25, 2015 Copyright © American Heart Association, Inc. All rights reserved.

Efficacy outcomes. Efficacy outcomes. Stroke or systemic embolism; stroke; ischemic or unknown type of stroke; hemorrhagic stroke; death from any cause; composite of stroke, systemic embolism, and death; and composite of stroke, systemic embolism, myocardial infarction, and death in patients with and without valvular heart disease treated with apixaban versus warfarin. *P value for the randomized treatment by valvular heart disease status interaction. CI indicates confidence interval; HR, hazard ratio; MI, myocardial infarction; and SE, systemic embolism. Alvaro Avezum et al. Circulation. 2015;132:624-632 Copyright © American Heart Association, Inc. All rights reserved.

Safety outcomes. Safety outcomes. ISTH major bleeding, intracranial bleeding, major or clinically relevant nonmajor bleeding, and any bleeding in patients with and without valvular heart disease treated with apixaban versus warfarin. *P value for the randomized treatment by valvular heart disease status interaction. CI, confidence interval; HR, hazard ratio; and ISTH indicates International Society on Thrombosis and Haemostasis. Alvaro Avezum et al. Circulation. 2015;132:624-632 Copyright © American Heart Association, Inc. All rights reserved.

Conclusions In a large contemporary clinical trial in patients with atrial fibrillation and an indication for oral anticoagulation, over a quarter of patients have a history of moderate or severe valvular heart disease or previous valvular surgery. There was no evidence of a differential effect of apixaban over warfarin in patients with and without valvular heart disease in reducing stroke and systemic embolism, causing less major bleeding, and reducing mortality With the exception of those with clinically significant mitral stenosis or mechanical prosthetic heart valves

Pazienti in cui i NAO vanno sicuramente o probabilmente evitati 1. FA valvolare (protesi meccaniche, valvulopatia mitralica severa) 2. FA da cause reversibili (ipertiroidismo non trattato, intervento cardiochirurgico, embolia polmonare…) 3. Ipertensione non controllata nonostante il trattamento (>180/100 mmHg [RE-LY, ARISTOTLE], > 170/100 mmHg [ENGAGE-AF]) 4. Recente ictus: precedenti 14 giorni (RE-LY, ROCKET-AF), 7 giorni (ARISTOTLE), 30 giorni (ENGAGE-AF) 5. Recenti emorragie gastrointestinali: precedenti 12 mesi (RE-LY), 6 mesi (ROCKET-AF), 12 mesi (ENGAGE-AF), ‘recente’ (ARISTOTLE) 6. Insufficienza renale severa: VFG < 30 ml/h (RE-LY, ROCKET- AF, ENGAGE-AF), < 25 ml/h (ARISTOTLE) 7. Intervento chirurgico maggiore già pianificato. 8. Hb < 9.0 g/dl (ARISTOTLE) o < 10 g/dl (altri trials) 9. Gravi malattie coesistenti

I condizionamenti normativi

Piani terapeutici AIFA per i NAO Apixaban Dabigatran Rivaroxaban Condizioni di ingresso Paziente con Fibrillazione Atriale Non Valvolare (FANV) cronica o parossistica Paziente con Fibrillazione Atriale Non Valvolare (FANV) Paziente con Fibrillazione Atriale Non Valvolare (FANV) permanente Ai fini dell'eleggibilità bisogna rientrare in una delle seguenti condizioni (1, 2 o 3) Gruppo 1 CHA2 DS 2 -VASc ≥1 e HAS-BLED >3 CHA2 DS 2 –VASc >3 Gruppo 2 TTR negli ultimi 6 mesi <70% TTR negli ultimi 6 mesi <60% Gruppo 3 Il trattamento anticoagulante non è attuabile per difficoltà oggettive ad eseguire i controlli di INR.

Having more effective or safer anticoagulants was not the original hypothesis for their development the original hypothesis was to find “non- inferior” agents compared with warfarin, with better acceptance because of the lack of need of frequent coagulation testing

Suggerimenti per il follow-up

Initiation and Structured Follow-up of Patients on NOACs

Checklist During Follow-up of Patients With AF on NOAC Therapy

conclusioni

Effective use of NOACS in clinical practice Patient selection – ADHERENCE Dose selection – creatinine clearance, age, weight Determine interval follow-up – structured follow-up!! Assess stability of renal function over time Blood pressure control Avoidance of concomitant antiplatelet therapy, when possible Package insert – avoid potent drug interactions, guidance on transitions

A possible guide for the choice of the best novel oral anticoagulant Prisco D, J Cardiovasc Med 2015

AVK nel 2015 ? Sì, perché… Se ben monitorati, gli AVK sono efficaci e sicuri come i NAO L’aderenza alla terapia con AVK è strettamente controllata Rarissime complicanze anche a lungo termine (a parte le emorragie) Molta esperienza clinica (antidoti, pazienti con pluri-patologie….) Costano pochissimo (a molti sembra un pregio)

AVK nel 2015 ? No, perché… Il monitoraggio può rivelarsi complicato e costoso Hanno un lento inizio di azione terapeutica = sono spesso necessarie complicate procedure di “bridging” Subiscono parecchie interferenze (farmaci, cibi, malattie renali o epatiche…) Costano pochissimo (per alcuni è un difetto…)

NAO e medicina generale

VobisNewSMagazinE Anno IV 2014

Test di laboratorio qualitativi e quantitativi per monitorare l’efficacia della terapia anticoagulante VobisNewSMagazinE Anno IV 2014

Interazioni farmacologiche VobisNewSMagazinE Anno IV 2014

Gestione degli imprevisti durante terapia VobisNewSMagazinE Anno IV 2014

Interventi chirurgici o procedure diagnostiche invasive VobisNewSMagazinE Anno IV 2014

Switching da una terapia anticoagulante ad un’altra VobisNewSMagazinE Anno IV 2014