D-dimer enhances risk targeted thromboprophylaxis in ambulatory cancer patients.

BACKGROUND Thromboprophylaxis for ambulatory cancer patients 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 VTE risk threshold for thromboprophylaxis. METHODS The AVERT trial compared thromboprophylaxis with apixaban to placebo among cancer patients 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, b) ≥8% and <8% 6-month VTE risk thresholds. RESULTS 574 patients were randomized in the AVERT trial, 466 (81%) with baseline D-dimer were included in the study. 237 subjects received apixaban, 229 received placebo. In the complete cohort, there were 13 (5·5%) VTE events in the apixaban arm compared to 26 (11·4%) events in the placebo arm (aHR-0·49 (0.25-0.95), p<0·05). Number needed to treat (NNT) to prevent one VTE=17. 82(35%) and 72(31%) patients in the apixaban and placebo arms, respectively had a 6-month VTE risk ≥8%. In this sub-group, 7(8·4%) VTE events occurred with apixaban and 19(26·3%) events with placebo (aHR-0·33 (0·14-0·81), p<0.05), NNT=6. Individuals with a VTE risk <8% derived no benefit from apixaban thromboprophylaxis (aHR-0·89 (0·30-2·65), p=0·84). Increased rates of overall bleeding were observed with apixaban in both the complete (aHR-2·11 (1·09-4·09), p<0.05) and ≥8% predicted risk cohorts (aHR-2·87 (0·91-9·13), p=0·07). CONCLUSIONS A 6-month VTE risk threshold of ≥8% increases the efficiency of risk targeted thromboprophylaxis in ambulatory cancer patients. IMPLICATIONS FOR PRACTICE Ambulatory cancer patients 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 to 17 in with 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.