Once a patient is stabilized on warfarin therapy, how often should he or she be monitored

Let’s revisit our patient KD, a 58-year-old male who had unprovoked deep vein thrombosis. He completed 3 months of initial anticoagulation therapy and elected to continue with indefinite warfarin therapy in order to reduce his future risk for venous thromboembolism (VTE), specifically pulmonary embolism (PE). KD has now been on warfarin for a total of 7 months and his international normalized ratio (INR) values have been consistently therapeutic (range of 2.1 to 3.1) over the last 3 months while taking warfarin 5 mg daily except for Mondays and Fridays when he takes 7.5 mg (total weekly dose 40 mg). 

As KD has been stable throughout his entire treatment duration and specifically over the past 3 months, he asks if he is still required to come into clinic every 4 weeks to have his INR checked. Can KD have the interval between his INR checks extended?

The Research

The CHEST guidelines1 recommend monitoring the INR every 4 weeks in most patients. However, in those patients who have been stable on warfarin therapy for at least 3 months, CHEST suggests that it is reasonable to consider extending the interval between INR checks to 12 weeks. CHEST defines stable as consistently therapeutic INR values while receiving a stable dose of warfarin. However, it is unclear whether the recommendation is truly evidence-based and ready for widespread implementation as it was based on a single study by Shulman et al.2

Shulman et al studied 250 patients to investigate whether extending the INR monitoring interval out to 12 weeks was as safe as monitoring it every 4 weeks.2 However, subjects included in the study had to be receiving the same warfarin for at least 6 months at study entry (as opposed to the CHEST-recommended 3 months). 

In the study, subjects in both groups were contacted at 4-week intervals for counseling an education; this was primarily done to maintain blinding between groups. Although there was no difference in the maintenance of a therapeutic INR—as measured by the time in the therapeutic range—between groups at the conclusion of the study, it is important to note that individuals in the extended-interval group did not go a full 12 weeks without physician contact as they would in the real world under the proposed 12-week follow-up period.

So did CHEST get the recommendation for extending the INR monitoring interval correct? The study had 2 main differences. First, patients were stable for 6 months and were contacted at least every 4 weeks in the clinical study whereas CHEST recommends only 3 months of stability prior to extending the INR interval to 12 weeks. Furthermore, per the CHEST guidelines,1 it is unlikely that patients would be contacted every 4 weeks between in-clinic INR appointments. Yet, despite these notable shortcomings between the available evidence and the CHEST recommendation, we still believe there are certain patients who can be considered for extended-interval INR monitoring. 

Clinical Application

We use the CHEST guidelines1 to identify patients who should be considered for extended-interval INR monitoring. Importantly, the risks and benefits of such a strategy should be discussed thoroughly with patients prior to extending the follow-up interval. With less frequent check-ups, there is a potential for a subtherapeutic or supratherapeutic INR to go unnoticed for a longer period of time—which in turn can potentially put the patient at risk for VTE or bleeding complications, respectively. Patients will not receive routine counseling regarding diet consistency and medication adherence, and screening for changes in medications will also not be done as consistently. 

Therefore, patient education on home monitoring for signs and symptoms of bleeding should be emphasized and patients should be counseled to contact the clinic should any questions or concerns arise between visits or if medications will be started or stopped. Communication will be paramount and a method to reliably communicate with the patient should be identified, whether electronically through messaging systems or via telephone contact. 

If issues are encountered, clinicians should not hesitate to bring patients into clinic to evaluate the INR to ensure it is still therapeutic, assess for changes in medications or diet, and assess for any signs or symptoms of bleeding or thrombosis. If the INR is therapeutic and no other concerns are evident, the patient can return to extended-interval monitoring if preferred; shortening the follow-up interval, even temporarily, should always be a consideration to ensure the safety of warfarin therapy. 

Recommended Strategy

Suitable patients for extended-interval INR monitoring are those who are adherent to therapy, have a stable dose of warfarin, and have a consistent diet. The patient must be evaluated for “overall suitability” (aside from just INR values) so consideration should be given to overall health and stability of concomitant disease states and medications. 

Once a suitable patient is identified and they are extensively counseled, we prefer to slowly extend the INR interval from 4 to 6 weeks, then 8 weeks, and finally, 12 weeks. This strategy is recommended for 2 reasons: 

• Slowly extending the interval allows the patient and clinician to get comfortable with the extended interval follow-up in a gradual manner, allowing for patients to return to a shorter INR monitoring interval in a timely manner if any problems or issues arise.

• If patients are stable for 12 weeks at the start of the increased monitoring interval, the additional 6- and 8-week intervals will add up to a total of 6 months of patient stability prior to 12-week extended interval monitoring, which is consistent with the available clinical evidence. 

Outcome of the Case

KD has been receiving a stable dose of warfarin for at least the last 3 months, which met the CHEST criteria for stability. Given that KD has been doing well with his warfarin throughout his entire treatment period, he appears to be a suitable candidate for extended-interval INR monitoring. Prior to pursuing such a strategy, KD would be extensively counseled on the potential risks and benefits and a method to reliably communicate with him would be established. 

If KD was agreeable, his next INR check would be scheduled for 6 weeks, followed 8-week, and then 12-week intervals. We would not hesitate to bring KD to clinic for an INR check should a situation arise and we would not hesitate to shorten the monitoring-interval if INR values become inconsistent or changes in health or medications occur.

The Take-Away

1. Some patients may be suitable for extended-interval INR monitoring. Patients who are adherent to therapy, have stable INR values and consistent diets, and overall have stable comorbid disease states and medication regimens can be considered.

2. CHEST recommends that patients with stable INR values for at least 3 months can be considered for extending the INR monitoring interval to 12 weeks. However, available clinical trial evidence suggests that patients should be stable for at least 6 months prior to extending the monitoring interval.

3. Prior to extending the monitoring interval, patients should be thoroughly counseled on the potential risks and benefits of extended-interval INR monitoring. A reliable method of communication should be established prior to starting the extended-interval strategy.

4. If the extended-interval strategy is pursued, we prefer to gradually extend the monitoring to 6-week, then 8-week, and finally, 12-week intervals. Clinicians should not hesitate to check the INR sooner should potential problems arise. 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. 

References:

1.Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: CHEST Evidence-Based Clinical Practice Guidelines. 2012;141(2 Suppl).

2.Schulman S, Parpia S, Stewart C, et al. Warfarin dose assessment every 4 weeks versus every 12 weeks in patients with stable international normalized ratios: a randomized trial. Ann Intern Med. 2011;155:653-659, W201-203.