Reversal or Repletion Treatment Strategies and Outcomes of Patients With Major Bleeding Events Managed in the Emergency Department: Large Real-Life Investigation in the Northwestern Healthcare District of Tuscany.

OBJECTIVE: To verify the incidence of bleeding events in patients on ongoing anticoagulant treatment in the real world and compare the results of different reversal or repletion strategies currently available for pharmacological treatment. METHODS: Patients managed in the emergency department (ED) with major bleeding events, on ongoing anticoagulation were stratified according to bleeding site and reversal or repletion therapy with andexanet alfa (ADX), idarucizumab (IDA), prothrombin complex concentrate (PCC), and vitamin K (Vit-K). ENDPOINT: Death at 30 days was compared in the subgroups with cerebral hemorrhage (CH) and gastrointestinal (GI) bleeding. RESULTS: Of the 809,397 visits in the years 2022-2023 at 6 EDs in the northwestern health district of Tuscany, 5372 patients with bleeding events were considered; 3740 were excluded due to minor bleeding or propensity score matching. Of the remaining 1632 patients with major bleeding, 548 on ongoing anticoagulation were enrolled; 334 received reversal or repletion agents. Patients with CH (n = 176) and GI bleeding (n = 108) represented the primary analysis cohorts in the study's strategic treatment assessment. Overall, 30-day survival of patients on ongoing aFXa treatment receiving on-label ADX versus off-label PCC showed a relative increase of 71%, while 30-day survival of patients on ongoing aFII receiving on-label IDA versus off-label PCC showed a relative increase of 30%; no substantial difference was found when comparing on-label PCC combined with Vit-K versus off-label Vit-K alone. Indeed, patients undergoing on-label ADX or IDA showed a statistically significant difference over off-label PCC (ADX vs. PCC: n = 15, events = 4, mean ± SD 82.50 ± 18.9, vs. 49, 13, 98.82 ± 27, respectively; analysis of variance [ANOVA] variance 8627; P < 0.001; posthoc test diff 32, 95% confidence interval: 28-35; P < 001; IDA vs. PCC: 20, 5, 32.29 ± 15.0 vs. 2, 1, 28.00 ± 0.0, respectively; ANOVA 1484; P < 0.001; posthoc test -29, -29 -29, respectively; P = n.d.). On-label PCC combined with Vit-K showed overall a slight statistically significant difference versus off-label Vit-K alone (52, 16, 100.58 ± 22.6 vs. 53, 11, 154.62 ± 29.8, respectively; ANOVA 310; P < 0.02; posthoc test 4, 0.7-7.2, respectively; P < 0.02). Data were confirmed in the group of patients with CH (ADX vs. PCC: n = 13, events = 3, mean ± SD 91.55 ± 18.6 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA variance 10,091, F = 261; P < 0.001; posthoc difference test 36, 95% confidence interval: 30-41; P < 0.001; IDA vs. PCC: 10, 2, 4.50 ± 2.5 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA 16,876,303, respectively; P < 0.001; posthoc test 41, 34-47, respectively; P < 0.001). On-label PCC combined with Vit-K showed an overall slight statistically significant difference compared with off-label Vit-K alone (P < 0.01 and P < 0.001 in the subgroups of CH and GI bleeding). CONCLUSIONS: Patients undergoing specific reversal therapy with on-label ADX or IDA, when treated with aFXa or aFII anticoagulants, respectively, showed statistically elevated differences in 30-day death compared with off-label repletion therapy with PCC. Overall, 30-day survival of patients on ongoing aFXa or aFII receiving on-label reversal therapy with ADX or IDA compared with off-label PCC repletion agents showed an increase of 71% and 30%, respectively.

Bleeding Events in Patients 75 Years of Age and Older Under Long-term Anticoagulant Therapy: A Real-life Study.

OBJECTIVE: To investigate the risk of bleeding events in older patients under oral anticoagulant with a 4-year survey of a catchment area with 197,722 inhabitants of whom 15,267 were on warfarin and 10,397 on direct oral anticoagulants (DOACs). METHODS: Patients presented to the Emergency Department with major bleeding were enrolled and stratified according to age ≥75 years and ongoing warfarin or DOACs. Primary endpoint was 1-month death. RESULTS: Out of 1919 major bleeding, those of patients ≥75 years of age were 1127 (59%) versus 792 (41%) <75 years of age, P < 0.0001. In patients ≥75 years of age, brain hemorrhage accounted for 612 (54%) patients, gastrointestinal hemorrhage for 301 (27%), hematuria for 104 (9%), and other hemorrhage for 108 (10%). In patients ≥75 years of age, those on warfarin accounted for 175 versus 53 on DOACs, without difference of Charlson Comorbidity Index (5.25 ± 1.92 versus 5.09 ± 1.61; P = 0.5824). One-month death in patients ≥75 of age versus <75 years of age accounted for 77 (4.0%) versus 20 (1.0%); P < 0.0001. One-month death in patients ≥75 of age on DOACs was very low, without difference versus <75 years and within DOACs. Among DOACs, absolute bleeding events showed differences as follows: 3 bleeding events for edoxaban versus 21 for dabigatran; P < 0.001; versus 16 for rivaroxaban, P = 0.006; and versus 13 for apixaban, P = 0.02. CONCLUSIONS: Major bleeding and 1-month death accounted for higher percentage in patients ≥75 years of age and in patients receiving warfarin. Among DOACs, edoxaban presented the lowest absolute rate of hemorrhage among the 4 available DOACs, without difference in mortality.