Novel Oral AntiCoagulants - SW Healthcare

1、 Xarelto (rivaroxaban) is subject to additional monitoring. Prescribing information is available at this meeting . Adverse events should be reported. Reporting Tel.: 01635 563 500, Fax.: 01635 563 703 Email: This meeting is organised and fully funded by BayerL.GB.MKT.02.2021.14660 February 2021Dr St

2、ephen JenkinsConsultant HaematologistRussells Hall Hospital DudleyDirect Oral AntiCoagulantsOral Direct Inhibitors (ODIs)Novel Oral Anticoagulants (NOACs) All are different terms for the same drugsThe NOACs Dabigatran - Pradaxa Rivaroxaban- Xarelto Apixaban- Eliquis Edoxaban- LixianaCE guidelines CG

3、180 Published date: June 2021AnticoagulationAnticoagulationAnticoagulation may be with apixaban, dabigatran etexilate, Anticoagulation may be with apixaban, dabigatran etexilate, rivaroxaban or a vitamin K antagonist.rivaroxaban or a vitamin K antagonist.1.5.2 Consider anticoagulation for men with a

4、CHA2DS2-VAScscore 1.5.2 Consider anticoagulation for men with aCHA2DS2-VAScscore of 1. Take the bleeding risk into account.new 2021of 1. Take the bleeding risk into account.new 20211.5.3 Offer anticoagulation to people with aCHA2DS2-VAScscore 1.5.3 Offer anticoagulation to people with aCHA2DS2-VAScs

5、core of 2 or above, taking bleeding risk into account.new 2021of 2 or above, taking bleeding risk into account.new 20211.5.4 Discuss the options for anticoagulation with the person and 1.5.4 Discuss the options for anticoagulation with the person and base the choice on their clinical features and pr

6、eferences.new 2021base the choice on their clinical features and preferences.new 2021RivaroxabanRivaroxaban1.5.9 Rivaroxaban is recommended as an option for the 1.5.9 Rivaroxaban is recommended as an option for the prevention of stroke and systemic embolism within its prevention of stroke and system

7、ic embolism within its licensed indication, that is, in people with nonvalvular licensed indication, that is, in people with nonvalvular atrial fibrillation with one or more risk factors such as:atrial fibrillation with one or more risk factors such as:Congestive heart failureCongestive heart failur

8、eHypertensionHypertensionAge 75years or olderAge 75years or olderDiabetes mellitusDiabetes mellitusPrior stroke or transient ischaemic attack.Prior stroke or transient ischaemic attack.This recommendation is fromRivaroxaban for the This recommendation is fromRivaroxaban for the prevention of stroke

9、and systemic embolism in people prevention of stroke and systemic embolism in people with atrial fibrillation(NICE technology appraisal with atrial fibrillation(NICE technology appraisal guidance256).2021guidance256).2021 The decision about whether to start treatment with rivaroxaban should be made

10、after an informed discussion between the clinician and the person about the risks and benefits of rivaroxaban compared with warfarin. For people who are taking warfarin, the potential risks and benefits of switching to rivaroxaban should be considered in light of their level of international normali

11、sed ratio (INR) control.Assessing anticoagulation control with vitamin K antagonistsAssessing anticoagulation control with vitamin K antagonists1.5.11Calculate the persons time in therapeutic range (TTR) 1.5.11Calculate the persons time in therapeutic range (TTR) at each visit. When calculating TTR:

12、at each visit. When calculating TTR:Use a validated method of measurement such as the Use a validated method of measurement such as the Rosendaal method for computerassisted dosing or Rosendaal method for computerassisted dosing or proportion of tests in range for manual dosingproportion of tests in

13、 range for manual dosingExclude measurements taken during the first 6weeks of Exclude measurements taken during the first 6weeks of treatmenttreatmentCalculate TTR over a maintenance period of at least Calculate TTR over a maintenance period of at least 6months.new 20216months.new 2021 1.5.12 Reasse

14、ss anticoagulation for a person with poor anticoagulation control shown by any of the following: 2INR values higher than 5 or 1INR value higher than 8 within the past 6months 2INR values less than 1.5 within the past 6months TTR less than 65%.new 2021 1.5.13 When reassessing anticoagulation, take in

15、to account and if possible address the following factors that may contribute to poor anticoagulation control: Cognitive function Adherence to prescribed therapy Illness Interacting drug therapy Lifestyle factors including diet and alcohol consumption.new 2021 1.5.14 If poor anticoagulation control c

16、annot be improved, evaluate the risks and benefits of alternative stroke prevention strategies and discuss these with the person.new 2021Warfarin Is An Effective Drug Ann Intern Med1999;131:492501Ann Intern Med1994;120120:897902Ann Intern Med1994;120120:897902AntiplateletsAntiplatelets1.5.15 Do NOT

17、offer aspirin monotherapy 1.5.15 Do NOT offer aspirin monotherapy solely for stroke prevention to people with solely for stroke prevention to people with atrial fibrillation.new 2021atrial fibrillation.new 2021The Vitamin K antagonists including Warfarin has been the mainstay of anticoagulation for

18、over half a centuryClinicians are intimately familiar with warfarin and there are clear guidelines for its use Monitoring for its anticoagulant effect is routinely available, and physicians and surgeons are aware of the need to interrupt warfarin for many interventional procedures There are establis

19、hed and highly effective treatment strategies for bleeding in patients receiving warfarin and for the management of unanticipated excess anticoagulant effectHowever warfarin has many undesired effects including interaction with:MedicationsFoods AlcoholResulting in over or under coagulation which can

20、 result in an adverse clinical outcome In addition to this frequent monitoring of the INR whilst taking warfarin can be burdensome, inconvenient and costlyWhat Are The Key Differences Between the NOACs and Warfarin N NNovel agentsNote All the NOACs have only been compared to Warfarin in the landmark

21、 Registration studiesComparison between studies is difficult due to inherent differences in study design including, blinding status, control group parameters, inclusion and exclusion criteriaThere have been no large head to head studiesEDITORIALA New Era for Anticoagulation in Atrial FibrillationJes

22、sica L. Mega, M.D., M.P.H.N Engl J Med 2021; 365:1052-1054September 15, 2021EDITORIALTARGETED ANTI-ANTICOAGULANTSKENNETH A. BAUER, M.D.N ENGL J MED 2021; 373:569-571AUGUST 6, 2021Strengths Large sample size Prospective design Independent endpoint adjudicationLimitations Single-arm, open-label study

23、Potential for selection bias Patient self-selection for risk of stroke or bleeding, and conscientious participation Investigators may have selected patients based around intact cognitive function Limited influence on data completeness in observational setting Outcomes not adjusted for baseline risk

24、factors 1. Camm AJ et al, Eur Heart J 2021; XANTUS is the first large, international prospective study to describe rivaroxaban use in a broad patient population with NVAF Patients were at lower overall risk than in the phase III ROCKET AF trialOver 96% patients receiving rivaroxaban did not experien

25、ce any of the outcomes of stroke/SE, treatment-emergent major bleeding or all-cause deathIn XANTUS, rivaroxaban demonstrated low rates of stroke/SE and major bleeding, including intracranial and GI bleedingIncidences of these outcomes generally increased with higher stroke risk scoresMajor bleeding

26、was mostly treated conservatively; reversal agents were rarely usedTreatment persistence and patient satisfaction were high 80% of patients remained on rivaroxaban 75% reported they were satisfied with their treatment at 1 year1. Camm AJ et al, Eur Heart J 2021; All NOACs are cleared to some extent

27、by the kidneys Dabigatran80% Rivaroxaban33% Apixaban25% Potential for drug accumulation in patients with severe renal impairment especially below eGFRs 10Any two INRs8Any three unexplained INRs 5 in any 6 month periodPolypharmacy especially if likely to have regular medications e.g. repeated antibio

28、ticsAny clinically significant bleed on warfarinAny embolic stroke or peripheral embolism on warfarinRequiring domiciliary phlebotomyPatient preferenceThough please note if a patient has a well controlled INR on warfarin there Though please note if a patient has a well controlled INR on warfarin the

29、re will be limited benefit (and potential risk) by switching from warfarin to the will be limited benefit (and potential risk) by switching from warfarin to the NOACs NOACs Newly diagnosed AF patient with risk factorsPatitents identified to switch to NOAC from existing anticoagulant1. GP to discuss

30、treatment options , risks and benefits2. Complete referral form to anti coagulant clinic (available from the GP Hub)3. Order at the time of referral unless already available within the last month:FBC, biochemisty for liver, kidney and bone and a clotting screen from a service which will report to DG

31、OHs.Anticoagulant clinic will ensure safe initiation and counselling of patient but NOT the choice of treatmentGP information letter sent for each patientGP to re check renal function at least annually if deteriotes patients may need to be referred back to clinic and anticoagulant changed to warfari

32、nRivaroxaban and Apixaban are licensed down to a CrCl of 15 ml/minPatients with renal impairment were excluded from the ROCKET-AF and EINSTEIN studies if they had a creatinine clearance (CrCl) of 30mmol/minPatients with a creatinine clearance of 50mmol/min only represented a small proportion (10%) o

33、f patients studied in ROCKET-AFSimilarly in ARISTOTLE patients with a creatinine clearance of 25mmolmin were excludedSimilarly in ARISTOTLE patients with a creatinine clearance of 50mmol/min only represented 17% of patients studiedFor practical purposes at RHH we define severe renal impairment as an

34、 eGFR 30mmol/minWe do NOT recommend Rivaroxaban or Apixaban for patients with an eGFR 30mmol/minWe recommend anticoagulation with warfarin for patients with eGFR 30mmol/minDrugs that interact with Rivaroxaban and are NOT recommended to be taken concomitantly are: Strong inhibitors of both CYP3A4 and

35、 P-gp (Increase Rivaroxaban plasma concentration) eg HIV protease inhibitors and Azole antifungals Strong inducers of CYP3A4 (Decrease Rivaroxaban plasma concentrations) Eg Rifampicin, Phenytoin, Carbemazipins, St Johns WortPatients who have undergone thrombolysis as part of acute treatment Pregnanc

36、y/Attempting conception Breast feeding Patients 2 the upper limit of normal &/or any evidence of chronic liver failure i.e. Child Pugh score B or above ) Low platelets 3,500 people anticoagulated with NOACs The very large majority of these patients are anticoagulated with RivaroxabanHowever we s

37、till have 5,000 patients anticoagulated with warfarinAs compared to 6,500 patients anticoagulated with warfarin when the NOACs were first introduced in November 2021Not Just NICE Approved for AF Also for VTE Orthopaedic thromboprophylaxis Secondary prevention in ACSSimilar issues with management reg

38、ardless of indication Dosing dependent on Renal Function Compliance Management of haemorrhagic complicationsPatients receive therapeutic LMWH until VTE radiologically confirmed This is to avoid logistical error and improve complianceWhen When radiologically confirmed (and no contraindication to radi

39、ologically confirmed (and no contraindication to Rivaroxaban): Rivaroxaban): Start Rivaroxaban when the next dose of therapeutic LMWH is due First 21 days of Rivaroxaban is prescribed (15mg BD dose) and simultaneously patient is referred to anticoagulation nursing team for counselling re anticoagula

40、tion Patient reviewed a second time by anticoagulation nursing team prior to day 21. A further 28 days of once daily Rivaroxaban is prescribed and patient is handed over to GP with standardised written information to patient and GP and duration of anticoagulation confirmedRenal failure with an eGFR

41、30 (caution/reduced dose with an eGFR of 30-50) Renal failure with an eGFR 30 (caution/reduced dose with an eGFR of 30-50) Other co-existing indications for anticoagulation (eg Mechanical heart valve)Patients who have undergone thrombolysis as part of acute treatment Patients who have undergone thro

42、mbolysis as part of acute treatment Pregnancy Pregnancy Breast feeding Patients 2 the upper limit of normal &/or any evidence of chronic liver failure i.e. Child Pugh score B or above ) Low platelets 50 Hypersensitivity to Rivaroxaban Concurrent use of KetaconazolePatients with Anti-Phospholipid

43、 SyndromePatients with Anti-Phospholipid SyndromePatients where there are concerns regarding absorptionPatients where there are concerns regarding compliancePatients where there are concerns regarding compliancePatients with active cancer/undergoing chemotherapy; these patients should receive Patien

44、ts with active cancer/undergoing chemotherapy; these patients should receive LMWH or enter into the SELECT-D study (comparing LMWH with Rivaroxaban)LMWH or enter into the SELECT-D study (comparing LMWH with Rivaroxaban)Warfarin is not going anywhere soon ! Patients with renal failure (eGFR Bleeding

45、events in NOAC-treated patientsSJenkinsetal,EHAPoster,2021Please noteMore litigation surrounds warfarin than any other medicationUsually related to poor communication Indication for anticoagulationDuration of anticoagulationConsequences of poor complianceInteractions Events occur with patients on an

46、ticoagulation Events occur with patients on anticoagulation Any AnticoagulantAny Anticoagulant However well managed However well managed History of Licensing/Availability Logistics of the Medication Trial Data Money!.Are we in a similar situation with the NOACs as we were with the ACE inhibitors 15

47、years ago.?The NOACs are: At least as effective as Warfarin Lower rates of the most feared complication of intracranial haemorrhage No monitoring required Far fewer interactionsAny Questions rivaroxaban tablet. Indication(s): Xarelto, co-administered with acetylsalicylic acid (ASA) alone or with ASA

48、 plus clopidogrel or ticlopidine, is indicated for the prevention of atherothrombotic events in adult patients after an acute coronary syndrome (ACS) with elevated cardiac biomarkers. 10mg Prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surger

49、y. 15mg/20mg Prevention of stroke & systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors such as congestive heart failure, hypertension, age 75, diabetes mellitus, prior stroke or transient ischaemic attack (SPAF). Treatment of deep vein thrombo

50、sis (DVT) & pulmonary embolism (PE), & prevention of recurrent DVT & PE in adults (see W&P for haemodynamically unstable PE patients). Posology & method of administration: Oral b.i.d. dose; patients should also take a daily dose of 75 100 mg ASA or a daily dose of 75 100 mg ASA i

51、n addition to either a daily dose of 75 mg clopidogrel or a standard daily dose of ticlopidine. Start Xarelto as soon as possible after stabilisation, including revascularisation for ACS; at the earliest 24 hours after admission & at discontinuation of parenteral anticoagulation. If dose is miss

52、ed take next dose, do not double the dose. 10mg Oral o.d. dose; initial dose taken 6 to 10 hours after surgery provided haemostasis established. 15mg/20mg Take with food SPAF: 20 mg orally o.d. DVT & PE: 15 mg b.i.d. for 3 weeks followed by 20 mg o.d. for continued treatment & prevention of

53、recurrent DVT & PE. All strengths - Refer to SmPC for full information on duration of therapy & converting to/from Vitamin K antagonists (VKA) or parenteral anticoagulants. Special populations: Patients undergoing cardioversion: Xarelto can be initiated or continued in patients who may requi

54、re cardioversion. Renal impairment: mild (creatinine clearance 50-80 ml/min) - no dose adjustment; /10mg - moderate (creatinine clearance 30-49 ml/min) no dose adjustment. Severe (creatinine clearance 15-29ml/min) - limited data indicate rivaroxaban concentrations are significantly increased, use wi

55、th caution. 15mg/20mg - moderate & severe renal impairment - limited data indicate plasma concentrations are significantly increased, use with caution SPAF: reduce dose to 15mg o.d., DVT & PE: 15 mg b.i.d. for 3 weeks, thereafter 20mg o.d. Consider reduction from 20mg to 15mg o.d. if patient

56、s bleeding risk outweighs risk for recurrent DVT & PE; All strengths - Creatinine clearance 75 years of age or with low body weight (60kg). Patients on treatment with Xarelto & ASA or Xarelto & ASA plus clopidogrel/ticlopidine should only receive concomitant treatment with NSAIDs if the

57、benefit outweighs the bleeding risk. All strengths- There is no need for monitoring of coagulation parameters during treatment with rivaroxaban in clinical routine, if clinically indicated rivaroxaban levels can be measured by calibrated quantitative anti-Factor Xa tests. Xarelto contains lactose. I

58、nteractions: Concomitant use with strong inhibitors of both CYP3A4 & P-gp not recommended as clinically relevant increased rivaroxaban plasma concentrations are observed. Avoid co-administration with dronedarone. Use with caution in patients concomitantly receiving NSAIDs, ASA or platelet aggreg

59、ation inhibitors due to the increased bleeding risk. Concomitant use of strong CYP3A4 inducers should be avoided unless patient is closely observed for signs and symptoms of thrombosis. Pregnancy & breast feeding: Contra-indicated. Effects on ability to drive and use machines: syncope (uncommon)

60、 & dizziness (common) were reported. Patients experiencing these effects should not drive or use machines. Undesirable effects: Common: anaemia, dizziness, headache, eye haemorrhage, hypotension, haematoma, epistaxis, haemoptysis, gingival bleeding, GI tract haemorrhage, GI & abdominal pains, dyspepsia, nausea, constipation, diarrhoea, vomiting, pruritus, ra