Warfarin and Atrial Fibrillation

Thu, 02/20/14 - 15:39

Authors:
Eric A. Dietrich, PharmD, BCPS, and Louis Kuritzky, MD
The advent of a variety of
methodologically new antithrombotic agents has provided clinicians with important choices to
make when selecting treatments for commonplace syndromes, such as atrial fibrillation,
pulmonary embolism, and deep venous thrombosis. Although newer agents show great promise,
they should in no way detract from the time-honored and the well-substantiated success of
warfarinwhich is still recommended by respected consensus groups, such as The American
College of Chest Physicians (AT9),
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as the preferred initial treatment for atrial fibrillation.
This column aims to establish a strong foundation in the fundamentals of appropriate
administration, monitoring, and management of warfarin. The goal is for primary care clinicians
to feel at home to initiate, monitor, and adjust dosing through the gamut of commonplace
scenarios one is likely to encounter.
Evidence-based guidelines are designed to help with clinical decision-making and come with a
warning that they are not a substitute for using your best judgment. While not every clinical
encounter is a double-blind, randomized, placebo-controlled answer, we will couple evidence-
based standards of treatment with therapeutic wisdom that stems from the experience of (most
usually) very successful management of patients requiring antithrombotic treatment in a primary
care clinic that is co-managed by clinical pharmacologists in concert with primary care
physicians.
What is Warfarin?
Warfarin, also known as dicoumarol, was discovered when grazing cattle experienced bleeding
after eating feed that was spoiled with sweet clover, which contains dicoumarol. Coumarin, the
parent compound of warfarin, is a synthetic version of dicoumarol. The name warfarin is derived
from its discovery at the University of Wisconsin as part of research funded by the Wisconsin
Alumni Research Foundation (WARF, leading to warf-) combined with the chemical class
coumarin (-arin) that warfarin belongs too.
How Does it Work?
Since it is impossible for anyone other than hematologists or overzealous medical and veterinary
students to remember all the steps of the coagulation cascade, suffice it to say that numerous
steps in the coagulation process are amenable to blockade resulting in hypocoagulability. For
several decades, the standard test to measure blood coagulability was the prothrombin time (PT),
commonly known as the Pro-time. The PT measured the time to clotting of a blood sample
compared to controlwhich in normal patients is 12 to 13 seconds.
As valuable as the PT was, it was not generalizable. That is, the PT at your local hospital would
differ (sometimes significantly) from the hospital across the street, since every test was
compared to a local onsite control that was not the same from lab-to-lab.
To the rescue came the international normalized ratio (INR), which inherently compensated for a
control, such that all laboratory sites could use the same method and come up with comparable
results. Normally coagulating blood has an INR of 0.9-1.1, and persons are considered
meaningfully (potentially therapeutically) anticoagulated when the INR is >2.0.
Anticoagulation with warfarin is not immediateit requires time. This is because depletion of
endogenous clotting factors takes time. Factor II (Table) has the longest half-life of active steps
in the coagulation cascade. Until factor II is appreciably reduced, warfarin cannot express its full
anticoagulant effects. Since, on average, it takes about 5 days to deplete factor II to a relevant
extent in healthy individuals, we do not typically anticipate seeing meaningful increments in
coagulation status until at least 5 days of warfarin administration.
A Case Study
Agatha is an 85-year-old woman with controlled hypertension (lisinopril 20 mg/d). She has just
moved to your community from another town. Her sister brought her in for a complaint of
irregular heart beat, which occurred every day for the last 3 weeks. She says her symptoms dont
really bother her, but it was noted that her heart rate was irregular when her sister measured her
blood pressure for the last several weeks. Your physical examination is unremarkable except for
an EKG that shows atrial fibrillation at 110 bpm.
Addressing Atrial Fibrillation
1. Risk stratification for stroke. The CHADS2 score is the most widely used risk stratification
tool for persons with atrial fibrillation. CHADS2 incorporates congestive heart failure (1 point),
hypertension (1 point), age over 75 years (1 point), diabetes mellitus (1 point), and history of
stroke or transient ischemic attack (2 points) to predict the risk of stroke. AT9 indicates that at a
CHADS score of 1 or greater antithrombotic therapy is recommended. Agathas CHADS score is
2 (age >75 years and hypertension). Therefore, she needs antithrombotic therapy.
2. Provide antithrombotic therapy for persons at sufficient risk as per AT9.
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After discussing
currently recommended treatments (warfarin, dabigatran, rivaroxaban, and apixiban), Agatha and
her sister agree to start warfarin.
3. Promptly initiate antithrombotic therapy. The most important aspects of taking warfarin are
consistency, diet, and interfering substances (a topic to be discussed in future cases).
We ask patients to administer their warfarin at night. Why? Most patient monitoring is done
during the day. In the event of a supratherapeutic INR, if the patient has not yet taken their daily
dose, we may omit or reduce it that same day. In the event the measured INR is subtherapeutic,
we may promptly (even that same morning) augment their dose.
Ultimately, however, consistency trumps time of day. If a patient remembers to take their
warfarin as part of their morning routine when they brush their teeth, but their nights are more
irregular, wed prefer to go with whatever best fits their lifestyle. It is more important to find a
consistent time of day that the patient is confident will lead to good adherence.
Whats the Take Home?
1. Patients with atrial fibrillation should first be risk stratified for the risk of stroke. CHADS2
and CHADSVasc are currently used, however the AT9 Guidelines recommend CHADS2 for its
simplicity.
2. AT9 recommendations suggest antithrombotic therapy for patients with atrial fibrillation and a
CHADS score of 1 or greater.
3. Administration of antithrombotic therapy at night may simplify management of out-of-range
INR results.
4. Consistency of dosing administration is paramount. Even though nocturnal dosing is preferred,
whatever time the patient feels will best suit consistency should be selected.
In the above case, the patient agreed to start warfarin. Our next column will cover how to initiate
and monitor warfarin treatment on Agatha.
Eric A. Dietrich, MD, graduated from the 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.
Louis Kuritzky, MD, is a family physician affiliated with the University of Florida Family
Medicine Residency Program, where he commonly co-manages warfarin cases with his
colleagues.
References:
1. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: CHEST Evidence-Based
Clinical Practice Guidelines. 2012;141(2 Suppl).
2. Coumadin [package insert]. Princeton, NJ: Bristol-Myers Squibb Pharma Company; 2011.