Vitamin K & Blood Thinners: New Hope for Kidney Patients?

randomized-controlled-trial PMID: 33753537

Quick Summary: A recent study found that for people on dialysis with an irregular heartbeat (atrial fibrillation), a blood thinner called rivaroxaban, sometimes with vitamin K2, may be safer and more effective than older blood thinners. This means fewer heart problems and less bleeding.

What The Research Found

Researchers looked at how well different blood thinners worked for people on dialysis who also had atrial fibrillation, a condition where the heart beats irregularly. They found that rivaroxaban, either alone or with vitamin K2, was better at preventing heart problems and caused less bleeding compared to a common blood thinner called a vitamin K antagonist (VKA).

Study Details

Who was studied: 132 people on dialysis with atrial fibrillation.

How long: The study followed patients for about 1.9 years on average.

What they took:

Some took a VKA (like warfarin), with their dose adjusted to keep their blood thinness at a certain level.
Some took rivaroxaban (10 mg daily).
Some took rivaroxaban (10 mg daily) plus vitamin K2, three times a week.

What This Means For You

If you're on dialysis and have atrial fibrillation, this research suggests that rivaroxaban, possibly with vitamin K2, could be a better option than older blood thinners. This could mean:

Fewer heart attacks and strokes: The study showed a lower risk of these serious events.

Less bleeding: Rivaroxaban, especially with vitamin K2, seemed to cause less dangerous bleeding.

Important Note: Always talk to your doctor before changing any medications or taking new supplements, including vitamin K2. They can help you decide what's best for your specific health situation.

Study Limitations

It's important to know that this study has some limitations:

Small Study: The study only included a small number of people, so the results might not apply to everyone.

Location: The study was done in Japan, so the results might be different for people in other parts of the world.

Not "Blind": The researchers and patients knew which treatment they were getting, which could have affected the results.

Stopped Early: The study was stopped before it was supposed to finish, which could affect the reliability of the results.

Vitamin K2's Role: The study didn't fully explain how vitamin K2 helps, so more research is needed.

Key Findings

The Valkyrie trial found that rivaroxaban (10 mg/day) alone or combined with vitamin K2 (45 μg thrice weekly) significantly reduced cardiovascular events and bleeding risks compared to vitamin K antagonists (VKAs) in hemodialysis patients with atrial fibrillation. The primary composite endpoint (fatal/nonfatal cardiovascular events) occurred at 63.8 per 100 person-years in the VKA group versus 26.2 in the rivaroxaban group and 21.4 in the rivaroxaban + K2 group. The rivaroxaban + K2 combination showed the lowest risk (competing risk-adjusted HR: 0.41, 95% CI: 0.25–0.68). Major bleeding rates were 16% for VKAs, 7% for rivaroxaban, and 4% for rivaroxaban + K2.

Study Design

This multicenter, open-label randomized controlled trial (RCT) enrolled 132 hemodialysis patients with atrial fibrillation in Japan. Participants were assigned to three groups: VKA (target INR 2–3), rivaroxaban 10 mg daily, or rivaroxaban 10 mg + vitamin K2 (menaquinone-4, 45 μg thrice weekly). Median follow-up was 1.88 years (IQR: 1.01–3.38), with treatment continuation post-18-month follow-up extension.

Dosage & Administration

VKA group: Dose-adjusted to maintain INR between 2 and 3.
Rivaroxaban group: 10 mg orally once daily.
Rivaroxaban + K2 group: 10 mg rivaroxaban daily + 45 μg vitamin K2 (menaquinone-4) thrice weekly.
All patients underwent hemodialysis thrice weekly.

Results & Efficacy

Primary endpoint: Rivaroxaban + K2 reduced event rates by 66% vs. VKA (HR: 0.41, 95% CI: 0.25–0.68). Rivaroxaban alone reduced rates by 59% (HR: 0.41 vs. VKA, though exact CI not provided).
All-cause mortality: Lower in DOAC groups (21.4 deaths/100 person-years for rivaroxaban + K2 vs. 38.5 for VKA).
Safety: Life-threatening/major bleeding occurred in 16% of VKA patients vs. 7% (rivaroxaban) and 4% (rivaroxaban + K2). Premature discontinuation occurred in 25% of participants overall.

Limitations

Small sample size: Only 132 patients, limiting generalizability.
Single-country population: Conducted in Japan, raising questions about applicability to other ethnicities.
Open-label design: Potential bias due to lack of blinding.
Early termination: The trial was stopped prematurely, possibly affecting long-term outcome reliability.
Unclear K2 mechanism: The role of vitamin K2 in enhancing rivaroxaban’s efficacy remains speculative without biomarker data.

Clinical Relevance

For hemodialysis patients with atrial fibrillation, rivaroxaban (with or without vitamin K2) may offer superior protection against cardiovascular events and bleeding compared to VKAs. However, the reduced dose of rivaroxaban (10 mg/day) and thrice-weekly vitamin K2 administration require careful monitoring in this population. Clinicians should weigh these findings against the study’s limitations, including early termination and regional demographics. The combination of rivaroxaban + K2 shows promise but needs validation in larger, global trials before routine adoption. Patients should not self-administer vitamin K2 without medical guidance, as interactions with anticoagulants may vary.

Source: PubMed (NCT03799822, 2021).