Low Dose Oral Vitamin K Does Not Increase Time in Therapeutic Range: Results of a Multicentre Clinical Trial
Bibliographic record
Abstract
Abstract Warfarin remains the most commonly used oral anticoagulant. Its efficacy is closely correlated with the time in therapeutic range (TTR) of the international normalized ratio (INR). Excellent anticoagulant management systems can achieve TTRs in excess of 80%: however, in day-to-day clinical practice TTR values in the range of 50 to 60% are more commonly seen. Strategies to increase TTR are widely sought; one such intervention is the daily administration of low dose vitamin K (VK) administered to reduce variations in VK intake and thus reduce fluctuations in the INR due to such variability. In this multicentre, blinded, randomized controlled trial we allocated patients on chronic warfarin therapy to receive either 0.150 mg of daily oral VK, or matching placebo. After a one month “run in period” to allow adjustment of the warfarin dose, patients were followed for a maximum of 9 months (mean 6 months), their INR was determined, their TTR calculated and their mean warfarin dose calculated. A total of 253 patients were enrolled at 4 clinical centres between Aug 19, 2010 and Aug 30, 2013; 18 (9 in each group) were excluded from this analysis due to inadequate follow-up data, mostly as a result of withdrawal from the study during the run in period. Of the 117 analyzable patients allocated to VK, 66 were male (average age 66.9 yrs). Of the 118 analyzable patients allocated to placebo 59 were male (average age 65.7 yrs). Indications for warfarin were similar between the two groups, as was the frequency of renal insufficiency and the presence of cancer. Patients allocated to placebo were more likely to report a history of bleeding (7% vs 3%). Mean TTR over the 6 months prior to enrollment to the study was 54.6% in the placebo group, and 51.8% in the VK group. Mean TTR over an average follow-up of 6 months after completion of the 1 month run-in period was 66% in the placebo group, and 65.1% in the VK group. We conclude that inclusion in this study resulted in a statistically (and likely clinically) significant improvement in the TTR. The improvement in the TTR we observed appeared to be predominately as a result of attentive clinical management, rather than administration of VK. Our findings do not support the use of daily, low dose oral vitamin K administered in an effort to improve TTR. Disclosures Crowther: Portola: Consultancy; Leo: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy; AKP America: Consultancy; Heart and Stroke Foundation: Career Investigator award Other; Celgene: Honoraria; Shire: Honoraria; CSL Behring: Honoraria. Lazo Langer:Pfizer: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; Leo Pharma: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria; Alexion: Research Funding; Daichii Sankyo: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Yeo:Bayer: Honoraria. Schulman:Boehringer Ingelheim: Consultancy, Honoraria, Research Funding; Bayer HealthCare: Consultancy, Honoraria, Research Funding.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.010 | 0.012 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.004 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".