AF and the New Oral Anti-CoagulantsEvidenced based approach. Adapted from ESC guidelines.

Dr Raj Chahal, Cardiology TraineeNovember 2013

Current State Of Play

Atrial Fibrillation (AF) is not a benign condition.

Increased risk of stroke.

Risk of stroke varies with risk factors.

Increase mortality hazard ratio aside from stroke risk.

Clinical Events (outcomes) affected by AF

Prevalence

The most common sustained cardiac arrhythmia

Hospital based prevalence data probably underestimates as often asymptomatic.

Prevalence doubles with each decade of age from 0.5% at age 50-59 to 9% at 80-89 years.

Risks factors of developing AF: Age (OR 2.1 Men, 2.2 Women) Diabetes (OR 1.4 Men, 1.6 Women) Hypertension (OR 1.5 Men, 1.4 Women) Valve disease (OR 1.8 Men, 3.4 Women)

Conditions predisposing to, or encouraging progression of AF

Stroke Risk

CHADS2 Cardiac Failure Hypertention Age over 75 Diabetes Stroke/TIA (2 points)

CHADS2 score and stroke rate

*The adjusted stroke rate was derived from the multivariable analysis assuming no aspirin usage; these stroke rates arebased on data from a cohort of hospitalised AF patients, published in 2001, with low numbers in those with a CHADS2 scoreof 5 and 6 to allow an accurate judgement of the risk in these patients. Given that stroke rates are declining overall, actualstroke rates in contemporary non-hospitalised cohorts may also vary from these estimates. Adapted from Gage BF et al.

AF = atrial fibrillation; CHADS2 = cardiac failure, hypertension, age, diabetes, stroke (doubled).

Risk factors for stroke andthrombo-embolism in non-valvular AF

AF= atrial fibrillation; EF = ejection fraction (as documented by echocardiography, radionuclide ventriculography, cardiaccatheterization, cardiac magnetic resonance imaging, etc.); LV = left ventricular; TIA = transient ischaemic attack.

Adjusted stroke rate according to CHA2DS2-VASc score

The HAS-BLED bleeding risk score

*Hypertension is defined as systolic blood pressure > 160 mmHg.

INR = international normalized ratio.

European Society of Cardiology (ESC)

CURRENT GUIDELINES…

Choice of NOAC

All have similar large studies with evidence of non-inferiority to warfarin.

Dosing DABIGATRAN 150mg/110mg bd RIVAROXABAN 20mg/15mg od APIXABAN 5mg/2.5mg bd

Reasons for reduced dose include Age >80 CrCl <50 for Dabigatran/Rivaroxaban CrCl <30 for Apixaban

Other Considerations

Limit of CrCl Dabigatran 30 Rivaroxaban 15 Apixaban 15

Storage Dabigatran cannot be put into blister packs

Drug interactions Amiodarone, Clarithromycin, Verapamil, ‘conazoles

Comparison of NOAC Trials

DABIGATRAN RIVAROXABAN APIXABAN

patients 18,113 14,264 18,201

f/u 2 yrs 707 days 1.8 yrs

Primary outcome(Hazard ratio)

150mg- 1.11% (0.66)110mg- 1.53% (0.74)

1.7%(0.79)

1.27%(0.79)

Major bleeding(Hazard ratio)

150mg- 3.11% (0.93)110mg- 2.71% (0.69)

3.6%(vs 3.4%)

2.13%(0.69)

Haemorragic stroke(Hazard ratio)

150mg- 0.30% (0.41)110mg- 0.23% (0.31)

0.5%(0.67)

0.24%(0.51)

GI bleeding Higher Higher Higher

Bleeding…

There is no antidote…

In Dabigatran dialysis may be helpful…

No clear evidence for use of Octiplex/Beriplex/Tranaxamic Acid…

Discontinuation of NOACs

“Hi is that the medics?… Surgeons here… just wanted some advice about…”

DISCONTINUATION OF DABIGATRAN

Timing of discontinuation after last dose of dabigatran before surgery

Renal function Half-life Standard risk High risk (CrCl mL/min) (hours) of bleeding bleeding

≥ 80 13 (11-22) 24 hours 2 days

≥ 50 to < 80 15 (12-34) 24 – 48 hours 2-3 days

>30 to < 50 18 (13-23) 48 – 72 hours 4 days

30* 27 (22-35) 2 – 5 Days > 5 days

*contra-indicated

DISCONTINUATION OF RIVAROXABAN

If an invasive procedure or surgical intervention is required, rivaroxaban should be stopped at least 24 hours before the intervention, if possible and based on the clinical judgement of the physician.If the procedure cannot be delayed the increased risk of bleeding should be assessed against the urgency of the intervention.

Rivaroxaban should be restarted after the invasive procedure or surgical intervention as soon as possible provided the clinical situation allows and adequate haemostasis has been established.

DISCONTINUATION OF APIXABAN

Apixaban should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of bleedingApixaban should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding including interventions for which any bleeding that occurs is expected to be minimal, non-critical in its location or easily controlled.

If surgery or invasive procedures cannot be delayed, appropriate caution should be exercised, taking into consideration an increased risk of bleeding against the urgency of intervention.Apixaban should be restarted after the invasive procedure or surgical intervention as soon as possible provided the clinical situation allows and adequate haemostasis has been established.