**2. Evaluation of the risk of tromboembolism and bleeding to recommend anticoagulant therapy in the AF**

Currently, there have been scales for assessing the risk of stroke and bleeding in patients with AF. The risk of stroke is classified into low, moderate and high, depending on the fac‐ tors set out in the CHADS2 scale (Table 2) [8]. A higher score greater risk. Patients at high risk should receive OACs and low risk, acetylsalicylic acid or nothing (prefer no treatment). In intermediate-risk patients should consider any of the two treatments.


**Table 2.** Stroke risk stratification with the CHADS2 score

Given the limitations of CHADS2 scale, a large proportion of patients are classified as inter‐ mediate risk and to the omission of potential risk factors for thromboembolism, there is the scale CHA2DS2-VASc [9,10]. This new scale is more comprehensive as additional risk factors: the presence of vascular disease, a younger age range than the CHADS2 and female category (Table 3). The patients with a grade of 0 are at low risk and should not be treated. The rest should be considered for oral anticoagulation, establishing the risk of bleeding by HAS-BLED scale (Table 4) [11]. In patients with a HAS-BLED score ≥3, caution and regular review are recomended and to correct the potentially reversible risk factors for bleeding. A high HAS-BLED score per se should not be used to exclude patients from OAC therapy.


**Table 3.** Stroke risk stratification with the CHA2DS2-VASc score


**Table 4.** HAS-BLED risk criteria

stratify each patient, both the risk of stroke such as bleeding, to individually assess what the

Due to the complexity of the use of VKAs in routine clinical practice in the last decade has developed an extensive research activity and has seen the introduction of new oral anticoa‐ gulants (NOACs): The direct thrombin inhibitors (dabigatran) and factor Xa (rivaroxaban and apixaban) that do not possess the disadvantages of the VKAs. These drugs are charac‐ terized by rapid onset of action, low potential for drug and food interactions and a predicta‐

ble anticoagulant effect that avoids the need to monitor coagulation (Table 1) [5-7].

Predictable anticoagulant effect No routine coagulation monitoring required

In intermediate-risk patients should consider any of the two treatments.

Diana enzymatic cascade specific clotting Low risk of adverse effects related to its mechanism of action

**2. Evaluation of the risk of tromboembolism and bleeding to recommend**

Currently, there have been scales for assessing the risk of stroke and bleeding in patients with AF. The risk of stroke is classified into low, moderate and high, depending on the fac‐ tors set out in the CHADS2 scale (Table 2) [8]. A higher score greater risk. Patients at high risk should receive OACs and low risk, acetylsalicylic acid or nothing (prefer no treatment).

> **CHADS2 acronym Score** Congestive Heart failure (CHF) 1 Hypertension 1 Aged ≥ 75 years 1 Diabetes mellitus 1 Stroke or transient ischemic attack (TIA) 2 **Maximum score 6**

best therapeutic approach in each case.

208 Atrial Fibrillation - Mechanisms and Treatment

**Comparative features of VKAs and NOACs**

**Table 1.** Comparative features of VKAs and NOACs

**anticoagulant therapy in the AF**

**Table 2.** Stroke risk stratification with the CHADS2 score

**Advantage Clinical implications** The rapid onset of action No bridge therapy required

Low potential for interactions with food No dietary restrictions Low potential for drug interactions Few drugs restrictions

> If a patient has a rating of less than 2 on the CHADS2 scale, it also assesses the amendment CHA2DS2-VASc, although this could be applied directly: if the score is zero, who are at low risk, with none of the risk factors, no antithrombotic treatment is indicated and if the score is

1, is preferred to administer OACs (VKAs or NOACs) based upon an assessment of the risk of bleeding complications and patient preferences. If CHA2DS2-VASc score equal to or great‐ er than 2, the treatment is with OACs (VKAs or NOACs) is recommended, unless contrain‐ dicated. When the patients refuse the use of OACs (VKAs or NOACs), antiplatelet therapy should be considered (combination therapy with acetylsalicylic acid plus clopidogrel).

prothrombin to thrombin in the early stage (stage start) and end (amplification / propaga‐

The search of ideal anticoagulant is one of the most active fields of investigation in lasts years. The ideal anticoagulant would be one that fulfilled the following characteristics: Oral administration, effective in the treatment of AF and low bleeding risk, predictable kinetics, which does not require monitoring of coagulation and platelet count, which is not necessary to adjust the dose, wide therapeutic range, low drug interaction, cost effective and availabili‐

With these premises have been developed more specific inhibitors of coagulation factors: factor Xa and factor II (thrombin). In Table 5, inspired by Phillips and Ansell collected some of the most relevant pharmacological characteristics of NOACs (dabigatran, ribaroxaban

**Warfarin Acenocoumarol Dabigatran Rivaroxaban Apixaban**

72-96 h 1,5-3 h 2-4 h 1-3 h

Vol. of dist. 60-70 l 50 l Reported as low

Half-life 40 h 8-11 h 12-14 h 9-13 h 9-14 h Metabolism Liver-CYP2C9 Liver- CYP2C9 Conjugation Liver-CYP3A4 and

Monitoring INR INR Not needed Not needed Not needed

Assay PT/INR PT/INR Experimental Experimental Experimental

VKOR: vitamin K oxidase reductase; CYP: cytochrome P450; PCC: prothrombin complex concentrates; PPIs: proton

Vitamin K, FFP, PCC or

Factor IIa (Thrombin)

20% faecal

Twice daily

FFP, PCC or rFVIIa

absorption and potent P-gp inhibitors

Factor Xa Factor Xa

New Oral Anticoagulants in Atrial Fibrillation

http://dx.doi.org/10.5772/53614

211

Once daily Twice daily

FFP, PCC or rFVIIa FFP, PCC or

Partially through CYP3A4

75% faecal, 25% renal

rFVIIa

Potent CYP3A4 inhibitors

CYP2J2

66% faecal, 33% renal

Potent CYP3A4 inhibitors and P-gp inhibitors

and apixaban) compared with VKAs (warfarin and acenocoumarol) [18].

VKOR and factors II,

VII,IX,X

Elimination Bile and urine Bile and urine 80% renal,

Administration Once Daily Once Daily Once or

rFVIIa

**Table 5.** Summary of pharmacokinetics and pharmacodynamics of VKAs and NOACs

Drug interactions CYP2C9 PPIs decrease

Vitamin K, FFP, PCC or rFVIIa

pump inhibitors; P-gp: P-glycoprotein; h: hour.

tion phase) the model based on the coagulation system.

**4. New oral anticoagulants**

ty of an effective antidote.

Target VKOR and

Time to peak concentration

Antidote or potencial therapy for bleedind

factors II,VII,IX, X

In patients with CHA2DS2-VASc score of 1, apixaban and both doses of dabigatran (110 mg twice daily and 150 mg twice daily) had a positive net clinical benefit while, in patients with CHA2DS2-VASc score ≥2, all three NOACs were superior to warfarin, with a positive net clinical benefit, irrespective of bleeding risk. The patients with CHA2DS2-VASc equal to 0 have a lower risk of stroke and could be left with acetylsalicylic acid or no treatment, prefer‐ ring the latter option, as it has not shown any benefit in this group without treatment.

When using dabigatran, the dose is 150 mg administered twice daily in patients with low risk of hemorrhage (HAS-BLED scale of 0 to 2) and 110 mg twice daily in patients with in‐ creased risk hemorrhage (HAS-BLED ≥ 3), elderly patients, concomitant use of interacting drugs and moderate renal impairment (creatinine clearance (CrCl) 30-49 mL/min) [12].When using rivaroxaban, the dose is 20 mg daily in the most patients and 15 mg daily en high bleeding risk (HAS-BLED ≥ 3) and moderate renal impairment (CrCl 30-49 mL/min) [13].
