NOACs: New Drugs You Cannot Afford Not to Master

The four NOACs have been approved for use in patients with non-valvular AF, DVT, PE and for preventing DVT following hip and knee surgery. In essence, with the exception of anticoagulation for mechanical valves, NOACs now cover every indication for which Coumadin is traditionally prescribed. 

MECHANISM OF ACTION OF TRADITIONAL AND THE NEWER ORAL ANTICOAGULANTS

The new oral anticoagulants work at sites different from Coumadin and are gaining acceptance because of their ease of use.

Coumadin interferes with coagulation by acting on four vitamin-K dependent coagulation factors (Figure 2). These factors are quite sensitive to changes in vitamin K availability.  Minor changes in diet or the use of antibiotics can affect these factors. It is therefore important to meticulously manage the level of anticoagulation (measured by PT/INR) in patients on Coumadin. Doses have to be carefully adjusted. 

Unlike Coumadin, NOACs act at sites quite close to the formation of the fibrin clot (Figure 2). The level of anticoagulation is therefore more predictable and the drugs can be given at a fixed dose without monitoring blood tests. There are also no dietary restrictions with these agents (Table 1). Patients and physicians find these features attractive and an increasing number of patients are now on Pradaxa and Xarelto.

Figure 2. Sites of Action of Coumadin, Xarelto, Eliquis, Savaysa (Factor Xa) and Pradaxa (Factor II)

In clinical trials, all NOAC agents have been as or more efficacious than Coumadin in preventing stroke in patients with non-valvular AF, in managing DVT or PE and in preventing DVT after hip and knee surgeries. In these trials, patients had fewer bleeding complications with the NOAC agents than with Coumadin.  

Table 1.  Comparison of Coumadin and NOACs

Although the degree of anticoagulation by NOACs can be measured by Ecarin Clotting Time (ECT), this test is rarely necessary because all the drugs give relatively predictable levels of anticoagulation. Dentists must decide whether it’s necessary to interrupt anticoagulation therapy. This depends on the procedure planned, the clinical scenario and the likelihood of bleeding complications.

For most non-surgical and simple surgical procedures, it’s reasonable to proceed with attention to local hemostatic measures without interrupting therapy.  This is based on an analogy drawn from managing patients on Coumadin, where interrupting Coumadin was found to have more risk than benefit. However, keep in mind NOACs have much faster onset and washout than Coumadin and relatively short half-life. 

A patient who is taken off either agent for 24 hours has a very short period with lessened anticoagulation. The risk of thrombus formation in patients during this short window is low. It is therefore theoretically safer to interrupt NOAC therapy than Coumadin therapy. However, the risk benefit ratio of transient interruption of therapy has not been clearly defined. It is important to include the patient’s physician in any decision that involves interrupting anticoagulation. Patients with significant risk of thrombosis have to be managed without interruption of therapy by careful use of local hemostatic measures.

Local hemostatic measures should include:

• Extra sutures

• Compressive packing and dressing

• Microfibrillar collagen hemostat

• Oxidized cellulose

• 4.8% tranexaminic acid mouthwash

• Tropical thrombin

For complex surgical procedures, it’s reasonable to consult with the patient’s physician to see if it is safe to interrupt NOAC therapy. 

For Pradaxa and Eliquis (BID drugs), the oral anticoagulant should be held the evening before the procedure and the morning of the procedure. Pradaxa and Eliquis should be resumed the evening after the procedure.

For Xarelto and Savaysa (QD drugs usually given in the evening), the medication should be held the evening before the procedure and resumed on the evening after the procedure.

In all instances, there is still residual anticoagulation and the patients should be warned about issues with hemostasis, but the short period of interruption should decrease the bleeding tendency.

ONE SHOULD NOT STOP ORAL ANTICOAGULANTS WITHOUT DOCUMENTATION OF THE OPINION OF THE MEDICAL CONSULTANTS

If the consulting physician deems the risk of interrupting the oral anticoagulants outweighs the benefit, it is then up to the dental professional to decide if the intended procedures can be done safely in the presence of full anticoagulation.

USE OF COMMONLY PRESCRIBED DRUGS IN DENTISTRY FOR PATIENTS ON NOACs

As is often the case, dental professionals should be aware of potential drug-drug interactions with these new oral anticoagulants. Drugs that interfere with the metabolism of these drugs should be avoided. Similarly, drugs that can increase bleeding complications also should be avoided.

I have included a page from the Ultimate Cheat Sheets for drugs that are safe to use and drugs that should be avoided in patients on Pradaxa (Table 2). Only drugs commonly prescribed by dentists are included. In instances where a drug prescribed is not on the list, it’s important to consult a source such as Lexicomp to be sure there is no drug-drug interactions with Pradaxa and Xarelto.

ACCEPTANCE OF THE NEWER ORAL ANTICOAGULANTS (NOACs)

It is clear the fixed dosage of NOACs, the elimination of PT/INR monitoring and the fact there are no dietary restrictions are attractive for patients and physicians alike. It is generally found in clinical trials that NOACs have similar efficacy and are safer than Coumadin.  There is therefore increasing use of NOACs clinically.

The previous concerns that these drugs do not have reversal agents are now addressed with the availability of Praxbind and Decoy Factor Xa. 

These drugs are now standard first line therapy for managing patients in AF, with DVT or PE and in the prevention of DVT after hip and knee surgeries.