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With its narrow therapeutic range, warfarin is a tricky drug to use.
Dosing depends on many factors, including interactions with other medications, certain foods, or over-the-counter supplements. Outside of its therapeutic range, warfarin can increase the risk of bleeding or conversely of developing blood clots. Patients had been advised to avoid vitamin K–rich foods so as not to counteract warfarin’s effects, although clinical guidance now recommends consistent intake instead.
But newer findings have weighed in with another option: increase vitamin K intake to maintain stable anticoagulation, and do it with food. At the American Society for Nutrition’s recent annual meeting, Guylaine Ferland, PhD, a professor of nutrition at the University of Montreal in Canada, reported findings from a small study that showed boosting daily dietary vitamin K consumption appears more effective at maintaining stable anticoagulation for patients with a history of warfarin instability than simply offering general dietary advice.
“These are foods most people eat anyway, it’s just that they have to introduce them into their usual diet in a more systematic manner and in perhaps a more well-informed manner,” Ferland said.
Although warfarin has been losing ground to the newer direct oral anticoagulants (DOACs) including apixaban and dabigatran, Ferland said the drug isn’t about to disappear from the anticoagulation landscape. “There remain a number of conditions that will call for warfarin,” such as mechanical heart valves and renal insufficiency, she said. Warfarin also is the drug of choice for antiphospholipid syndrome, noted Paige Christensen, NP, associate medical director of thrombosis and anticoagulation for Intermountain Healthcare in Salt Lake City.
“This conversation and these dietary interests in vitamin K probably aren’t going to go away for a long time,” Christensen added.
The 46 patients in Ferland’s randomized controlled trial had been treated with warfarin for more than 6 months, but their anticoagulation status was in the therapeutic range less than half the time. The study’s primary clinical end point was having warfarin levels in the therapeutic range more than 70% of the time from 4 to 24 weeks. Being in the therapeutic range at least 70% of the time has been associated with a reduced risk of stroke and lower death rates.
About half of the patients received general dietary information. The other half received dietary counseling on specific foods they could eat to increase their vitamin K consumption by 150 μg daily along with recipes and cooking instructions. At the end of the study, 50% of patients in the dietary counseling group met the clinical end point compared with 20% in the control group.
Ferland noted that previous research has shown that higher vitamin K intake was associated with more stable anticoagulation with warfarin. But some studies weren’t randomized or they used a supplement rather than food. “The idea to aim for the same kind of vitamin K you would get with a low-dose supplement but doing this through food was appealing to me,” Ferland explained.
“We think that by increasing daily intake there will be a bit more that is stored in the liver,” she said. “On a day when someone doesn’t eat as much for some reason, the impact on…anticoagulation will not be as dramatic.”
Christensen said she found the study promising. “[I]t makes sense clinically with what we see every day with our patients,” she added. In her practice, clinicians educate patients to keep their vitamin K intake consistent. Compared with avoidance, she said, “patients seem to be more compliant and tended to have more success” in maintaining stable anticoagulation with warfarin.
What’s more, she noted, the variety of foods in the study’s dietary plan provide additional nutrients and they appeal to her patients’ palate.
Ferland’s study focused on 3 food groups—leafy green vegetables as well as cabbages, broccoli, and lettuces; oils; and fresh or dried herbs. She and her colleagues met with study participants in the intervention group once a month for nutrition talks, a cooking lesson, or other discussions. The participants also received written information about the most commonly consumed green vegetables, oils, and herbs. Ferland and her colleagues came up with easy ways to describe the equivalent of 150 μg of vitamin K in the foods participants were encouraged to eat.
Some of the participants devised their own strategies to get their daily 150 μg. “They would have a smoothie every morning with kale and mango,” Ferland said. “They knew they had their 150 μg and then they could forget about [it] for the rest of the day.”
Given the emphasis on maintaining consistent daily vitamin K intake, it’s important to keep in mind that too much of a certain food can tip the scales. At UC San Diego Health’s anticoagulation clinic, that food often is kale, a vitamin K powerhouse with 531 µg of vitamin K in a cooked, half-cup serving. Clinical pharmacist Megan Lang, PharmD, asks patients upfront when she meets them about their kale intake. The vegetable is so popular in San Diego that Lang said she feels “like kale is on its own island.”
Some of her patients also blend it in smoothies, but for others—those receiving chemotherapy cycles that ruin the appetite for a few days, elderly patients who eat poorly, or college students with erratic eating habits—Lang uses an over-the-counter vitamin K supplement to ensure consistent intake. The supplement is inexpensive and “then [patients] don’t have to worry about grocery shopping,” she added.
Ferland plans to submit her data for publication, but she’s still crunching data. A question she thinks physicians would like to have answered is whether the dietary intervention would entail increasing patients’ warfarin dosage. “This is what we’re computing,” from patient records during the 6-month study, she said.
A natural next step, she added, is comparing outcomes of patients who take warfarin and follow the increased vitamin K food plan with those who take DOACs. The newer drugs sometimes are considered superior because they have a wider therapeutic range than warfarin, so patients don’t need to be monitored as often and they don’t need to watch their diet as closely. The DOACS are less likely to cause brain bleeds but more likely to result in gastrointestinal bleeding.
The DOACs also are far more expensive. Christensen estimated that the out-of-pocket DOAC cost is $300 to $400 per month compared with $10 to $30 for warfarin. With some insurance plans, warfarin can be had for a $5 co-pay. Depending on insurance coverage, Christensen said the monthly DOAC cost could range between $50 and $250. “For many…it tips them over the edge,” she added. What’s more, the cost of reversing DOACs with a factor Xa inhibitor for patients who experience uncontrolled bleeding is $25 000 to $50 000 at Intermountain Health, Christensen said. Warfarin is reversed with vitamin K.
Ferland said that while the merits of warfarin vs DOACs continue to be debated, her early findings offer a relatively easy, accessible way to boost the likelihood of stabilizing anticoagulation for people who take warfarin. “I’m quite convinced the dietary intervention is beneficial,” she said.
Voelker R. Green Vegetables, Herbs, and Oils May Help Stabilize Patients Taking Warfarin. JAMA. Published online September 04, 2019. doi:10.1001/jama.2019.13060
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