D-Dimer Enhances Risk-Targeted Thromboprophylaxis in Ambulatory Patients with Cancer
Bibliographic record
Abstract
BACKGROUND: Thromboprophylaxis for ambulatory patients with cancer is effective, although uncertainties remain on who should be targeted. Using D-dimer values from individuals enrolled to the AVERT trial, we sought to identify and validate a more efficient venous thromboembolism (VTE) risk threshold for thromboprophylaxis. MATERIALS AND METHODS: The AVERT trial compared thromboprophylaxis with apixaban with placebo among patients with cancer with a Khorana Risk Score ≥2. The D-dimer measured at randomization was used to calculate an individualized 6-month VTE risk using the validated CATScore. A modified intention-to-treat analysis was used to assess efficacy (VTE) and safety (major and overall bleeding) in the (a) complete cohort and (b) ≥8% and < 8% 6-month VTE risk thresholds. RESULTS: Five hundred seventy-four patients were randomized in the AVERT trial; 466 (81%) with baseline D-dimer were included in the study. Two hundred thirty-seven subjects received apixaban; 229 received placebo. In the complete cohort, there were 13 (5.5%) VTE events in the apixaban arm compared with 26 (11.4%) events in the placebo arm (adjusted hazard ratio [aHR] 0.49 [0.25-0.95], p < .05). Number needed to treat (NNT) to prevent one VTE = 17. Eighty-two (35%) and 72 (31%) patients in the apixaban and placebo arms, respectively, had a 6-month VTE risk ≥8%. In this subgroup, 7 (8.4%) VTE events occurred with apixaban and 19 (26.3%) events with placebo (aHR 0.33 [0.14-0.81], p < .05), NNT = 6. Individuals with a VTE risk <8% derived no benefit from apixaban thromboprophylaxis (aHR 0.89 [0.30-2.65), p = .84). Increased rates of overall bleeding were observed with apixaban in both the complete (aHR 2.11 [1.09-4.09], p < .05) and ≥ 8% predicted risk cohorts (aHR 2.87 [0.91-9.13], p = .07). CONCLUSION: A 6-month VTE risk threshold of ≥8% increases the efficiency of risk-targeted thromboprophylaxis in ambulatory patients with cancer. IMPLICATIONS FOR PRACTICE: Ambulatory patients with cancer receiving chemotherapy have an increased risk of venous thromboembolism (VTE). A Khorana Risk Score (KRS) ≥2 is currently the suggested threshold for thromboprophylaxis. Using baseline D-dimer values from individuals enrolled to the AVERT trial, this retrospective validation study identifies a 6-month VTE risk of ≥8% as a more efficient threshold for thromboprophylaxis. At this threshold, the number needed to treat to prevent one VTE is 6, compared with 17 when using a KRS ≥2. Conversely, individuals with a predicted risk of <8% derive no clinical benefit from thromboprophylaxis. Future prospective studies should validate this threshold for outpatient thromboprophylaxis.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".