The Indian consensus guidance on stroke prevention in atrial fibrillation: An

emphasis on practical use of nonvitamin K oral anticoagulants

DR VIRBHAN BALAI

Practical suggestions have been formulated in the following clinical situations:

1. Dose recommendations of the NOACs in different clinical scenarios;

2. NOACs in patients with RHD3. Monitoring anticoagulant effect of the NOACs; 4. Overdose of NOACs; 5. Antidotes to NOACs; 6. Treatment of HCM with AF using NOACs; 7. NOACs dose

Introduction

AF is the most common sustained cardiac arrhythmia

Important risk factor for cardioembolic stroke.NVAF is associated with a 5-fold increased

risk of stroke.Valvular AF on the other hand is associated

with a 17- fold increased risk of stroke.Prevalence of 0.6% in the Indian subset.

The prevalence of paroxysmal AF as reported in the RE-LY, REALIZE, and IHRS-AF study was 38%, 43%, and 19.5%, respectively.

Perma-nent AF was reported in 18.6%, 34.3%, and 33.7% of participants in the RE-LY, REALIZE, and IHRS-AF study, respectively.

Every year, 20 million people worldwide experience a stroke. In the Asia-Pacific region, China and India have the

maximum number of deaths resulting from stroke.Approxi-mately 15% of all strokes are associated with AF.

Stroke risk assessment

CHA2DS2-VASc score of 0 (age <65 years with 'lone AF' [individuals without clinical or echocardiographical evidence of cardiopulmonary disease, including hypertension])and

CHA2DS2-VASc score of 1 (female patients aged <65 years and with 'lone AF') are 'truly low-risk' patients and antithrom- botic therapy should not be considered

Antithrombotic therapy should be considered for those with CHA2DS2-VASc score of equal to or more than 1 in males and equal to or more than 2 in females.

Bleeding risk assessment

Three bleeding risk assessment tools have been derived and validated in patients with AF.

1. HEMORR2HAGES (hepatic or renal disease, ethanol abuse, malignancy, older age [≥75 years], reduced platelet count or function, rebleeding risk, hypertension [uncontrolled], anemia, genetic factors, excessive fall risk, and stroke).

1. HAS- BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normal- ized ratio [INR], elderly [e.g., age >65 years, frailty, etc.], drugs/ alcohol concomitantly),

2. ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation)

The HAS-BLED score has been validated in multiple cohorts.

A high HAS-BLED score (≥3) is predictive of major bleeding during bridging of chronic anticoagulant therapy.

Incidence of intracerebral hemorrhage is the highest among the Asians.

Validation of both the CHA2DS2- VASc and the HAS-BLEED scores is required in the Indian population.

Oral antithrombotic agents

• Vitamin K antagonist (VKA) • Until 2009, vitamin K antagonist (VKA) (such as

warfarin) was the only class of oral anticoagulant approved for the

Target INR- For the primary prevention of stroke Patients >75 years, a target INR of 2 (range 1.6–

2.5).For patients < 75 years - 2.5 (range 2–3)

Patients receiving warfarin spent 61% of time within, 13% of time above, and 26% of time below the therapeutic range (INR range 2–3).

Reduction in stroke was the highest (79%) when the patients spent at least 70% of time within the therapeutic range.

The risk of mortality was reduced by 81% in warfarin users who spent at least 70% of time in the therapeutic range.

Limitations of vitamin K therapy

Amiodarone may themselves affect INR .Warfarin-related nephropathy- is a newly described

entity in those with an acutely increased INR of more than 3 soon after the initiation of warfarin.

CKD and INR exceeding 3, the one-year mortality was 31.1% compared with 18.9% without warfarin- related nephropathy.

Hence, the INR should be kept below 3 in all patients soon after starting warfarin.

Nonvitamin K oral anticoagulants (NOACs)

The NOACs fall into two major categories: Direct thrombin (factor IIa) inhibitors -

Dabigatran Direct factor Xa inhibitors -rivaroxaban,

apixaban, and edoxaban.

As com-pared to warfarin, these NOACs have a predictable pharmaco- kinetic profile and fewer food-drug and drug-drug interactions, and do not require routine anticoagulant monitoring.

Dabigatran received the US FDA approval to prevent stroke in patients with NVAF in 2010.

This was followed by rivaroxaban approval in 2011 and apixaban approval in 2012.

Edoxaban received the US FDA approval in 2015.

Efficacy and safety of NOACs versus warfarin in NVAF

Dabigatran reduced stroke (or systemic embolism) by 35% and apixaban reduced it by 21%.

More importantly, only dabigatran 150 mg BID showed a significant reduction in the incidence of ischemic stroke.

All NOACs reduced the risk of hemorrhagic stroke when com-pared with warfarin.

NOACs in Asian population

• Analysis of the RE-LY trial revealed that the rates of bleeding outcomes (major, GI major, life-threatening major, minor, total, intracranial, and hemorrhagic stroke) when on warfarin were numerically higher in the Asian subjects than in non-Asians.

Management of acute coronary syndrome in atrial fibrillation

Stroke management in patients on NOACs: (<4.5 h of symptom onset)

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