**5. Monitoring of NOACs**

The NOACs not require routine monitoring. However, there are situations where it is advis‐ able to monitor selected patients as those with extreme weights, kidney failure or those who suffer thrombotic complications being treated with these drugs.

As a result of the occurrence of serious adverse effects, including severe gastrointestinal bleeding (81 cases) and deaths (260 cases) of bleeding in patients treated with dabigatran were published safety ratings by the rating agencies worldwide drug advising monitoring of renal function in patients with moderate renal impairment (30-50 mL/min) receiving dabi‐ gatran and in patients over 75 years. Rivaroxaban is contraindicated if CrCl <15 mL/min, and should be used with caution if is 15-30 mL/min.

Monitoring is also useful to evaluate the adherence to treatment (the omission of one or more doses puts the patient at risk of complications at an early stage) or when the patient needs to undergo an invasive procedure. When subjecting a patient to an invasive proce‐ dure, it is important to note that the drug half-life (12-14 hours dabigatran, rivaroxaban 9-13 hours and apixaban 9-14 hours). If the invasive procedure has a low bleeding risk, it is suffi‐ cient to suspend the drug 24-36 hours before surgery and if no complications arise, resume anticoagulant treatment at 36-48 hours [23].

Thus, in a patient treated with dabigatran and rivaroxaban that presents a mild bleeding complication, it is advisable to delay the next drug administration or discontinuation. If bleeding is moderate or severe, symptomatic treatment is indicated as mechanical compres‐ sion standard, surgical hemostasis bleeding control procedure, blood products and hemody‐ namic support (packed red cells or fresh frozen plasma). In the case of very severe bleeding will require charcoal filtration or haemodialysis or administration of an agent for reversing the specific procoagulant effect, such as prothrombin complex, the prothrombin complex

concentrate or activated recombinant factor VIIa. In this case, experience is limited.

advantage of inducing a lesser extent intracerebral hemorrhages (Table 6).

Study design Randomized open

Follow-up period,

Randomized groups

Primary endpoint: stroke and systemic embolism (in % per

Major bleeding events

years

year)

label

Dose-ajusted WA vs. blinded doses of DA (150 mg BID, 110 mg BID)

1.71% WA 1.54% DA 110mg 1.11% DA 150mg

3.57% WA 2.87% DA 110mg 3.32% DA 150mg

**Table 6.** Summary of the main clinical trials with NOACs

**7. Evaluation of scientific evidence, relevance and limitations of the study**

It will analyze the scientific evidence, the limitations of design and the clinical relevance of the results of published clinical trials (RE-LY, ROCKET AF, AVERROES and ARISTOTLE). In general, these new drugs are at least equally effective and safer than warfarin, with the

**Dabigatran Rivaroxaban Apixaban**

Multicenter, randomized, doubleblind, double-dummy

Dose-ajusted WA vs. RI 20 mg OD

> 2.42% WA 2.12% RI

> 3.45% WA 3.6% RI

BID: twice daily; OD: once daily; WA: warfarin; DA: dabigatran; RI: rivaroxaban; API: apixaban; AAS: acetylsalicylic acid

Number of patients 18.113 14.264 5.599 18.201 Mean age 71.5 years 73 years 70 years 70 years Male:female ratio 63.6%: 36.4% 60%:40% 58.5%: 41.5% 64.7%: 35,30%

Mean CHADS2 score 2.1 3.5 2.1 2.1

**(RE-LY) (ROCKET AF) (AVERROES) (ARISTOTLE)**

2 years 1.9 years 1.1 years 1.8 years

Multicenter, randomized, doubleblind, doubledummy

New Oral Anticoagulants in Atrial Fibrillation

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

215

AAS 81-324 mg OD vs. API 5 mg BID

> 3.9% AAS 1.7% API

> 1.2% AAS 1.4% API

Multicenter, randomized, doubleblind, doble-dummy

Dose-ajusted WA vs. API 5 mg BID

> 1.60% WA 1.27% API

> 3.09% WA 2.13% API

The ideal test for monitoring of direct thrombin inhibitors is the coagulation time of ecarin, with a linear relationship, and a good slope and discriminate levels of dabigatran in plasma. The problem is that it is non-standardized and few laboratories possess it.

The studies suggest that dabigatran monitoring will be done with a variant of thrombin time (TT). TT is very sensitive, with a linear relationship, but with a high slope, so that at low concentrations of dabigatran, TT extends above the detection limit of the coagulometer. It is a very good from a qualitative point of view, to assess adherence to treatment, but cannot quantify levels. The thrombin time will be a diluted thrombin time, marketed as Hemoclot®, which manages to improve the linear relationship with respect to TT and discriminate be‐ tween low, intermediate and high dabigatran in plasma [24].

Monitoring of rivaroxaban will be done by a method chromogenic anti-factor Xa. This test is marketed as anti-Xa assay. Is a sensitive and accurate, useful to measure the maximum and minimum plasma concentrations of rivaroxaban [25,26].
