How to Talk to Patients About the Novel Oral Anticoagulants
We have been following KD, a 58-year-old male with an unprovoked deep vein thrombosis (DVT) through his warfarin initiation and continuation. Recently, we gradually extended his international normalized ratio (INR) monitoring interval from every 4 weeks to every 12 weeks due to his history of consistency with his warfarin. His INR values continue to remain well-controlled and he does not have any problems with bruising, bleeding, or changes in medication or diet.
During one of his follow-up visits, he asks about a new drug called Eliquis (apixaban, Bristol-Myers Squibb/Pfizer) that he has seen a lot of TV commercials. He says the ads claim it is better than warfarin and wonders whether or not he should switch.
Should KD switch to a novel agent?
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RELATED CONTENT
Drug Interactions with Novel Oral Anticoagulants
Anticoagulation: An Update for Primary Care
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Marketing Blitz
Over the past couple of years 3 novel oral anticoagulants (NOACs) have been FDA approved: dabigatran (Pradaxa, Boehringer Ingelheim), rivaroxaban (Xarelto, Janssen), and apixaban. Originally approved for atrial fibrillation (AF), these agents have gained additional approval for the initial treatment of and long-term prevention of DVT and pulmonary embolus (PE).
Aggressive advertising campaigns have pushed these drugs to the forefront of consumers’ minds, often leading to similar questions as the one posed by KD. While some patients may be appropriate for the new agents, many are not—most notably advanced age and decreased renal function (among other patient factors) may lead to an unacceptably high rate of bleeding with the NOACs, and these events can be fatal.1
Physician–Patient Interactions
Here is an example of how we typically approach this conversation with our patients. The goal is to fully educate our patients on the NOACs and how they compare to warfarin. We start by discussing the issues related to monitoring as this aspect of NOACs use is generally the trigger that started the conversation (eg, hearing that NOACs do not require blood checks).
Monitoring
Clearly with warfarin, regular and routine INR checks are an essential step to ensure that the risks for bleeding and venous thromboembolism are minimized. The NOACs do not require routine monitoring—a point that is consistently and clearly indicated in the TV ads. That is because there is currently no reliable and accurate way to quantify the degree of anticoagulation afforded by the agent. Although this inability to monitor does seem a little unsettling, it is partly because these new agents produce consistent therapeutic effects and a way to routinely monitor them was not a high priority.
Similar to enoxaparin (most patients are familiar with this, especially individuals whose index event was a DVT or PE), these agents produce consistent effects in a many different patients, which makes monitoring the majority of the time unnecessary. However, there are times when knowing the degree of anticoagulation would be important—most notably during bleeding.
Safety
We know there is no way to monitor the degree of anticoagulation with the NOACs. However, when compared with warfarin, both dabigatran and rivaroxaban had similar overall risks for major bleeding, with the exception of higher bleeding into the GI tract.
Apixaban, on the other hand, had a lower risk for major bleeding compared with warfarin, although this does not mean bleeding with apixaban does not occur. Close monitoring of the INR, adherence with therapy, and consistency in diet can all help to minimize the risks for bleeding with warfarin.
If bleeding does occur with warfarin, there are ways to help reverse its anticioagulant effects. When administered, vitamin K begins to reverse the INR within 12 to 24 hours, depending on the route it is given and dosage. Blood products and other medications can also be given to help reverse warfarin’s effects and stop bleeding.
There is currently no way to reliably reverse the anticoagulant effect of the NOACs if major bleeding were to occur. The NOACs only work for about 12 hours, so when the drug is stopped, the effects are nearly gone after 24 hours (similar to the time course for vitamin K).
Selecting the appropriate patients and monitoring kidney function are important factors to minimize the risks for bleeding with the NOACs. Even though the NOACs claim to not require any routine monitoring, there still is some monitoring that is required to ensure the risks for bleeding are minimized.
Efficacy
In head-to-head comparisons with warfarin, dabigatran and apixaban are more effective at reducing the risks for stroke compared to warfarin in AF. Rivaroxaban is also thought to work as well as warfarin.
For the prevention of DVT and PE, all the new agents work as well as warfarin. However, how well these agents work compared to warfarin when the INR is very well-controlled is still unclear. It is generally thought that when the INR is very well-controlled, the NOACs are similar to warfarin and not better. Finally, warfarin has been shown to be cardioprotective, an effect that is not routinely seen in the NOACs. For certain patients, this protective effect can be very desirable.
Costs and Other Considerations
The NOACs are considerably more expensive than warfarin, which is available on the $4 medication lists from many national pharmacy chains. However, it is noteworthy to mention that NOACs do not have any dietary considerations and the list of interacting medications is considerably smaller than warfarin.
Both dabigatran and apixaban are dosed twice daily, which may hinder adherence in some patients. Rivaroxaban is dosed once daily; for AF, it must be taken with an evening meal, which limits the flexibility of a true “once -daily” medication.
Because NOACs only work for roughly 12 hours, a missed dose could leave a patient without anticoagulation for a considerable amount of time. It takes much longer for the therapeutic effects of warfarin to dissipate, making the potential consequences of the occasional missed dose less severe.
Outcome of the Case
Although KD could be considered for one of the NOACs, we would prefer to continue on warfarin as he is stable and does not have significant issues related to dietary indiscretion or problems coming to clinic for INR checks. For patients who are concerned, recent extension of the INR monitoring intervals could help alleviate the burden of INR monitoring.
The Take-Away
• The NOACs can be useful for certain patients in certain settings. Although they do not require routine monitoring, there currently is not a way to determine the degree of anticoagulation produced.
• In cases of excessive anticoagulation and bleeding, there is no reliable method or intervention to rapidly reverse the anticoagulant effects.
• The NOACs do provide consistent anticoagulation in most patients, and for those incurring a large burden associated with frequent trips to clinic for INR monitoring, they can be advantageous.
• However, for patients very stable on warfarin, the NOACs likely do not provide additional protection against blood clots as compared to warfarin. In those patients who are very stable, the INR monitoring interval can be extended to help alleviate the burden associated with frequent monitoring. ν
Eric A. Dietrich, PharmD, BCPS, graduated from UF College of Pharmacy in 2011 and completed a 2-year fellowship in family medicine where he was in charge of a coumadin clinic. He now works for the UF Colleges of Pharmacy and Medicine.
Reference:
1.Harper P, Young L, Merriman E. Bleeding risk with dabigatran in the frail
elderly. N Engl J Med. 2012;366:864-866.