Atrial Fibrillation and Anticoagulation Dr Mark Merrick GP Hannage Brook Medical Centre Wirksworth Meeting funded by Bayer HealthCare L.GB.MKT.07.2015.11874 July 2015 X-Impact is organised and funded by Bayer HealthCare. This meeting contains promotional content.

This meeting has been organised and funded by Bayer. Xarelto (rivaroxaban) prescribing information is available on request at this meeting   Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Bayer plc. Tel : 01635 563500 Fax : 01635 563703 Email : pvuk@bayer.com

Prevalence of AF

Stroke in AF Patients with AF have a five-fold higher stroke risk than those without AF AF doubles the risk of stroke when adjusted for other risk factors Without preventive treatment, each year approximately 1 in 20 patients (5%) with AF will have a stroke It is estimated that 15% of all strokes are caused by AF and that 12,500 strokes per year in England are directly attributable to AF

AF strokes are severe strokes 20% are fatal 60% are disabling Compared to non AF strokes:- 70% increased hospital mortality 40% decrease in chance of discharge home 20% increase length of hospital stay

Risk reduction with warfarin Reduces relative risk of stroke by approx 65 % Absolute risk reduction:- Primary stroke 2.7 % Secondary stroke 8.4 % Numbers needed to treat for 1 year to prevent 1 stroke:- Primary stroke 37 Secondary stroke 12 Overall 25 (approx)

NOACS Studies show to be at least as effective and probably more effective than Warfarin at stroke reduction in AF

Days since randomization ROCKET AF – Primary efficacy endpoint Stroke or systemic embolism 120 240 480 600 720 1 2 3 4 5 6 840 360 Cumulative event rate (%) Warfarin Rivaroxaban Days since randomization Number of subjects at risk Rivaroxaban▼ 6958 Warfarin 7004

ASPIRIN There is no role for aspirin in the treatment of AF It may be used in conjunction with an anticoagulant if there is coexisting vascular disease eg MI, PAD

CHA2D2S2 VASC ITEM SCORE Congestive Heart Failure or Left Ventricular Dysfunction 1 Hypertension 1 Age >/= 75 2 Diabetes 1 Stroke/TIA 2 Vascular disease (MI, PAD) 1 Age (65-74) 1 Sex category (female) 1

CHA2D2S2 VASC Score Annual Stroke Rate 0 0.8% 1 2% 3 3.7% 4 5.9% 5 9.3% 6 15.3% 7 19.7% 8 21.5% 9 23.6%

HAS-BLED SCORE

NICE June 2014 Anticoagulation may be with apixaban, dabigatran, rivaroxaban or a vitamin K antagonist Discuss the options for anticoagulation with each patient and base the choice on their clinical features and preferences

Which Anticoagulant?

Warfarin- Pros Warfarin has been prescribed for more than 50 years. Warfarin remains an established and cost effective option for anticoagulation in patients. Can be used in valve disease including valve replacement. INR gives clinicians a guide to patient compliance. Effective and familiar use of antidote with vitamin K should a severe bleed occur whilst being treated. Clearance of warfarin is not affected by renal function. For patients with poor adherence, long half life may be advantageous

Warfarin - Cons Warfarin - time to peak effect ranges from 3-5 days and a half-life averaging 40 hours. Warfarin is known to interact with many food and drugs Patients may have difficulty around complying with or accessing INR monitoring Narrow therapeutic range Poor INR control associated with increased morbidity and mortality

NICE Guideline for AF (June 2014) Review TTR at each visit (exclude 1st 6 weeks and must be over a period of ≥ 6/12): Reassess if over the past 6 months: x2 INRs > 5 or x1 INR > 8 or x2 INRs < 1.5 TTR < 65% Try to correct and take into account reasons for poor control: Cognitive function Adherence Illness Interacting drug Rx Lifestyle inc.diet and EtOH If cannot be improved consider other strategies

NOACS - PROS As well tolerated as warfarin No food and minimal drug interactions Predictable anticoagulant response (no A/C monitoring) Fixed dosing As or more effective than warfarin Rapid onset and offset of action

NOAC - CONS Short half life – missed does means inadequate anticoagulation Cost Renal function determines dose. Not suitable for severe renal impairment. Does require baseline tests and ongoing monitorring Not suitable for valvular AF No known antidote

Bleed risks of NOACs NOACS all have lower risk of Intracranial Bleeds Warfarin has slightly lower GI bleed risk than Rivaroxaban and Dabigatran (trials use different criteria so no head to head data) GI bleeds on NOACS seem less severe

Renal Function and NOACS All NOACs are a reasonable choice in mild to moderate CKD Estimated Creatinine Clearance should be calculated to determine dose. Cockroft-Gault equation uses age ,weight and serum creatinine) CrCl> 50 ml/min: No dosing adjustments required CrCl30-50 ml/min: use lower dose CrCl15-30 ml/min: do not use dabigatran

Safe Prescribing of NOACs Counselling the importance of strict adherence to therapy is the most crucial aspect of NOAC Rx (reinforce at every FU) Routine monitoring: Hb and liver function (annually) Renal function: Annually for CKD stage I–II (CrCl≥60 ml/min) 6 monthly for CKD stage III (CrCl30–60 ml/min) 3 monthly for CKD stage IV (CrCl≤30 ml/min) Regular (3 monthly) follow up: Counselling Side effects Medication review (interactions)

Drug Interactions Verapamil (use lower dose dabigatran) Amiodarone Dronedarone “Azole” antifungals HIV protease inhibitors Rifampicin, St John’s wort and phenytoin (drugs that affect CYP and P450)

Switching Warfarin to a NOAC: INR < 2.0: start NOAC immediately INR 2.0-2.5: start NOAC the next day NOAC to warfarin: Initiate warfarin with NOAC concomitantly until INR ≥ 2 Re-test INR 24hrs after NOAC discontinuation Missed doses: pt should take forgotten dose up till 6h (if bd NOAC) or 12h (if od NOAC) after scheduled intake otherwise skip dose and take next dose as scheduled

Hannage Brook AF Audit 11/14 - Practice size 8500 - Number on AF register 207 - Score of 2 or more but no anticoagulation 63 Score of 1 (no anticoag) 8 Score 2 or more on aspirin 40 Score 1 on aspirin 4

Nottingham City CCG: The Huge opportunity in Af 750 AF patients undiagnosed •In addition, use of CHA2DS2-Vasc instead of CHADS2and reducing exception reporting for anticoagulation to less than 15%, a further 2000high risk AF patients could be anticoagulated This will likely result in: 56 fewer strokes per year 19 fewer deaths per year £660,000 reduction in AF stroke related hospital admission costs per year

Discussion Choosing which anticoagulant Fear of new drugs Patients worried re change (esp if on aspirin) Worried not having INR Compliance Medidose Domiciliary patients GP-Pharmacy communication