Managing AF in Patients with Complex Comorbidities and Over the Long Term

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Mechanisms of AF and Relation to Disease States1 Diabetes Heart failure Obesity Coronary artery disease Valvular heart disease Hypertension Hyperthyroidism Renal impairment Anaemia Sepsis Surgical procedures Ageing Genetic predisposition Stretch-induced atrial fibrosis Hypocontractility Fatty infiltration Inflammation Vascular remodelling Ischaemia Ion channel dysfunction Ca2+ instability Electrolyte abnormalities Hyperstimulation of myocardial tissue Sympathetic overstimulation Reference 1. Kirchhof P, Benussi S, Kotecha D et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37: 2893-962. Reference: 1. Kirchhof P et al. Eur Heart J 2016; 37: 2893-962.

Mr P Aged 79 years, 65 kg Hypertension and dyslipidaemia Diet-controlled diabetes Persistent AF Stroke 2 years ago without any residual weakness. Alzheimer’s disease – MMSE 23 Medications include a NOAC and perindopril

Mr P’s Renal Function Deteriorates Following Yearly Check-up Recommendations Class Level Assessment of kidney function by serum creatinine or creatinine clearance is recommended in all AF patients to detect kidney disease and for correct dosing of therapy. I A All AF patients treated with oral anticoagulation should be considered for at least yearly renal function evaluation to detect chronic kidney disease. IIa B Reference 1. Kirchhof P, Benussi S, Kotecha D et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37: 2893-962. Reference: 1. Kirchhof P et al. Eur Heart J 2016; 37: 2893-962.

Dose Reductions of NOACs in Renal Disease Apixaban1 no dose adjustment is necessary in patients with mild or moderate renal impairment. Contraindicated for patients with CrCl <25 mL/min Dose adjustment recommended if serum creatinine ≥133 μmol/L, age ≥80 years, body weight ≤60 kg Rivaroxaban2 Adjust dose from 20 mg to 15 mg o.d. in patients with CrCl 30-49 mL/min Contraindicated for patients with CrCl < 30 mL/min Dabigatran3 In NVAF patients with moderate renal impairment (30-50 mL/min CrCL), a dose reduction from 150 mg b.d. to 110 mg b.d. may be considered Contraindicated for patients with CrCl <30 mL/min References: ELIQUIS Approved Product Information. XARELTO Approved Product Information. PRADAXA Approved Product Information. References: 1. ELIQUIS Approved Product Information. 2. XARELTO Approved Product Information. 3. PRADAXA Approved Product Information.

Renal Dysfunction – Key Considerations Assess1 Before initiating NOAC If a decline in renal function is suspected Review1 Yearly 6-monthly if CrCl 30–60 mL/min Taking dabigatran etexilate >75 years of age Fragile Reference 1. Heidbuchel H, Verhamme P, Alings M et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015; 17: 1467-507. Reference: 1. Heidbuchel H et al. Europace 2015; 17: 1467-507.

Mr P Requires Surgery Mr P presents to the surgery for removal of a skin lesion on his left arm (small lesion requiring approx. 4 sutures). Considerations: Patient factors:1 renal function, age, history of bleeding complications, concomitant medications Estimation of thromboembolic risk 1 Major factors include presence of atrial fibrillation, prosthetic heart valves, and recent venous or arterial thromboembolism (eg, within the preceding three months) CHA2DS2-VASc score Estimation of procedural bleeding risk1 High risk (coronary artery bypass surgery, kidney biopsy, and any procedure lasting >45 minutes) 2-day risk of major bleeding 2 to 4% Low risk (cholecystectomy, carpal tunnel repair, and abdominal hysterectomy) 2-day risk of major bleeding 0 to 2% Does Mr P need to stop his NOAC prior to the procedure? If so, how soon before? Examples of high bleeding risk procedures include coronary artery bypass surgery, kidney biopsy, and any procedure lasting >45 minutes; low bleeding risk procedures include cholecystectomy, carpal tunnel repair, and abdominal hysterectomy. Importantly, these categories do not substitute for clinical judgement or consultation between the surgeon and other treating clinicians. (Lip) NOACs during surgery: Patient factors including renal function, age, history of bleeding complications, concomitant medications and surgical factors should be considered prior to discontinuing the drug. Compared with warfarin, which may need bridging anticoagulation in patients with higher thromboembolic risks, patients on NOACs are less likely to require bridging therapy. This is explained by the short halflife which allows for properly timed short-term cessation and early reinitiation after surgery.2 References 1. Lip GY, Douketis JD. Perioperative management of patients receiving anticoagulants. <http://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants?source=search_result&search=Perioperative+management+of+patients+receiving+anticoagulants&selectedTitle=1~150> [Accessed 30/12/2016]. 2. Rahman A, Latona J. New oral anticoagulants and perioperative management of anticoagulant/antiplatelet agents. Aust Fam Physician 2014; 43: 861-6. Reference: 1. Lip GY et al. In: Uptodate.com (Leung LLK, ed), Vol. 2016: Wolters Kluwer, 2016. 2. Rahman A et al. Aust Fam Physician 2014; 43: 861-6.

Interactive question Does Mr P Need to Stop His NOAC Prior to the Procedure? (small lesion requiring approx. 4 sutures) Yes, to minimise the risk of bleeding, 7 days before surgery Yes, to minimise the risk of bleeding, 24 hours before surgery Only if there is a concern of bleeding, 7 days before surgery Only if there is a concern of bleeding, 24 hours before surgery Cessation of NOACs is not necessary before surgery ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where bleeding would be non-critical in location or easily controlled.(Eliquis PI)

Reference Periprocedural Management of Anticoagulation Writing C, Doherty JU, Gluckman TJ et al. 2017 ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients With Nonvalvular Atrial Fibrillation: A Report of the American College of Cardiology Clinical Expert Consensus Document Task Force. J Am Coll Cardiol 2017. In Press Reference: 1. Periprocedural Management of Anticoagulation Writing C et al. J Am Coll Cardiol 2017. In Press. .

Reference Periprocedural Management of Anticoagulation Writing C, Doherty JU, Gluckman TJ et al. 2017 ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients With Nonvalvular Atrial Fibrillation: A Report of the American College of Cardiology Clinical Expert Consensus Document Task Force. J Am Coll Cardiol 2017. In Press Reference: 1. Periprocedural Management of Anticoagulation Writing C et al. J Am Coll Cardiol 2017. In Press. .

Cessation Before Surgery: Who Makes the Decision? Major surgery: GP is able to make recommendation, specialist opinion may be required if there is doubt Minor surgery (e.g. dentistry): GP may be asked to make recommendation Clinical assessment on when to stop and start therapy Bridging therapy may not be required in NVAF for patients taking a NOAC.1 Discussion Reference 1. Douketis JD, Spyropoulos AC, Kaatz S et al. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. N Engl J Med 2015; 373: 823-33. Reference: 1. Douketis JD et al. N Engl J Med 2015; 373: 823-33.

Mr P Presents Following ACS Mr P presented to the ED with ACS and underwent a percutaneous coronary intervention and received a stent 6 months ago He is now on triple therapy of a NOAC + aspirin 75 mg/day + clopidogrel 75 mg/day He has a calculated CHA2DS2-VASC score of 1 and a low-moderate HAS-BLED score What medication changes would you make?

Mr P presents following ACS. What medication changes would you make Mr P presents following ACS. What medication changes would you make. Would you? Move to dual OAC therapy after 6 months and monotherapy after 12 months Move to dual therapy after 1 month and OAC monotherapy after 12 months Move to dual therapy after 1 month and OAC monotherapy after 6 months Either 2 or 3 above depending on bleeding risk The following guidelines slides provide the answer

Antithrombotic Therapy after an Acute Coronary Syndrome in Atrial Fibrillation Patients Requiring Anticoagulation Reference 1. Kirchhof P, Benussi S, Kotecha D et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37: 2893-962. Reference: 1. Kirchhof P et al. Eur Heart J 2016; 37: 2893-962.

Antithrombotic Therapy After Elective Percutaneous Intervention in Atrial Fibrillation Patients Requiring Anticoagulation Reference 1. Kirchhof P, Benussi S, Kotecha D et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37: 2893-962. Reference: 1. Kirchhof P et al. Eur Heart J 2016; 37: 2893-962.

Mr P’s Alzheimer’s Disease Deteriorates (MMSE 14) He is Admitted to an Aged Care Facility Factors that would influence the decision to cease therapy Aged care facility Renal failure High HAS-BLED High risk of falls QOL issues apart from dementia Family or Power of Attorney input as to level of intervention requested

Create a Management Plan For All Patients DO Evaluate AF for underlying cardiovascular conditions Propose lifestyle changes to suitable AF patients Use oral anticoagulation unless they are at low risk for stroke based or have contraindications Reduce all modifiable bleeding risk factors Check ventricular rate and use rate control medications to achieve lenient rate control DO NOT Use antiplatelet therapy for stroke prevention in AF Permanently discontinue oral anticoagulation in AF patients at increased risk of stroke unless such a decision is taken by a multidisciplinary team Use rhythm control therapy in asymptomatic AF nor in patients with permanent AF This is the final slide. Use this checklist to overview the key points in AF management and reiterate the issues highlighted in this presentation. Reference 1. Kirchhof P, Benussi S, Kotecha D et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37: 2893-962. Reference: 1. Kirchhof P et al. Eur Heart J 2016; 37: 2893-962.

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