Ahmed, Azza

Background: Reduced or low-dose direct oral anticoagulants (DOACs) have been studied in randomized control trials for the extended prevention of venous thromboembolism (VTE) after 6 months of treatment at full, therapeutic doses. The real-world effectiveness as well as utilization of this approach in clinical practice compared to continuing at therapeutic doses is unclear. Aims: Examine the effectiveness, safety and utilization of reduced-dose DOACs in cancer patients and overweight patients. Methods: Consecutive patients with VTE were identified using the Mayo Clinic VTE Registry from March 1st, 2013 to December 31st, 2021. Patients were followed prospectively for outcomes of VTE recurrence, death, major bleeding and clinically relevant non major bleeding (CRNMB) either in person or by survey. Patients with recurrent VTE or bleeding during the first 3 months were excluded from further analysis. After completion of anticoagulation treatment for 3 months with either rivaroxaban or apixaban, patients continuing anticoagulation were evaluated in a nested case-control study. Results: A total of 404 patients (283 (70%) on apixaban and 121 (30%) on rivaroxaban) were identified in the low dose DOAC and 3060 in the full dose anticoagulation group. Overall, the mean age was 60.7 years (SD 14.4), mean weight was 89.9 kg (SD 23.8) and 55.1% were males. Within the full cohort, patients with active cancer were less likely to be prescribed low dose DOACs (HR 0.56; 95%CI 0.42-0.73; p<0.001). However, low dose DOAC prescription was more likely in patients with pulmonary embolism alone (HR 1.48; 95%CI 1.21-1.80; p<0.001) or in combination with DVT (HR 1.54; 95%CI 1.25,1.90; p<0.001). Patients transitioned to low dose DOACs had similar age, sex and weight compared to the full dose anticoagulation group, however, fewer patients with weight ≥120 kg had reduced dosing (HR 0.68; 95%CI 0.46,0.99; p=0.046). The mean time to start of a low dose DOAC was 5.1 months overall, 5.4 months in cancer patients, and 3.6-4.9 months in non-cancer patients (Table 1). Non-cancer patients had significantly lower transition numbers in those ≥120kg (HR 0.62; 95%CI 0.40,0.97; p=0.038). In non-cancer patients In comparing weight, ≥120kg to <120kg, in the low dose group, only death was statistically different with higher risk in those ≥120kg (HR 6.44; 95%CI1.27,32.81; p=0.025). Cancer patients transitioned to low dose DOACs around 5 months on average with a median of 3.3 months. Apixaban continued to be the dominant DOAC used (78%) in the low dose group. The cancers with the most patients on low dose DOACs include lymphoma, prostate, melanoma, ovarian, and breast. There was no significant difference in VTE recurrence or death in the cancer group on different DOAC doses. Conclusion: Our results show that anticoagulant prescribers are not always waiting until 6 months to transition to low doses and low doses are being utilized in cancer patients despite lack of cancer-specific studies during the analyzed time period. Although the sample size limits the precision of this analysis, we did not find statistically significant increases in VTE recurrence with low dose DOACs in either cancer patients or with elevated body weight. We did find CRNMB but not MB was observed more frequently in weights above 120kg, possibly from unadjusted confounding in this unadjusted analysis.

Background. Acute kidney injury (AKI) is a well-known complication following a transcatheter aortic valve replacement (TAVR) and is associated with higher morbidity and mortality. Objective. We aim to compare the risk of developing AKI after transfemoral (TF), transapical (TA), and transaortic (TAo) approaches following TAVR. Methods. We searched Medline and EMBASE databases from January 2009 to January 2021. We included studies that evaluated the risk of AKI based on different TAVR approaches. After extracting each study’s data, we calculated the risk ratio and 95% confidence intervals using RevMan software 5.4. Publication bias was assessed by the forest plot. Results. Thirty-six (36) studies, consisting of 70,406 patients undergoing TAVR were included. Thirty-five studies compared TF to TA, and only seven investigations compared TF to TAo. AKI was documented in 4,857 out of 50,395 (9.6%) patients that underwent TF TAVR compared to 3,155 out of 19,721 (16%) patients who underwent TA-TAVR, with a risk ratio of 0.49 (95% CI, 0.36–0.66; p < 0.00001 ). Likewise, 273 patients developed AKI out of the 1,840 patients (14.8%) that underwent TF-TAVR in contrast to 67 patients out of the 421 patients (15.9%) that underwent TAo-TAVR, with a risk ratio of 0.51 (95% CI, 0.27–0.98; p = 0.04). There was no significant risk when we compared TA to TAo approaches, with a risk ratio of 0.89 (95% CI, 0.29–2.75; p = 0.84). Conclusion. The risk of post-TAVR AKI is significantly lower in patients who underwent TF-TAVR than those who underwent TA-TAVR or TAo-TAVR.

Abstract Background: Reduced or low-dose direct oral anticoagulants (DOACs) have been studied in randomized control trials for the extended prevention of venous thromboembolism (VTE) after 6 months of treatment at the therapeutic doses. The real-world effectiveness as well as utilization of this approach in clinical practice compared to continuing at therapeutic doses is unknown. Aims: Evaluate the efficacy of reduced-dose DOACs compared to standard therapeutic anticoagulation in patients with extended anticoagulation. Methods: Consecutive patients with VTE were identified using the Mayo Clinic VTE Registry from March 1st , 2013 to December 31st, 2020. Patients were followed prospectively for outcomes of VTE recurrence, death, major bleeding and clinically relevant non major bleeding (CRNMB) either in person or by survey. Type of anticoagulation and dose changes were recorded, and progressing to a low dose was treated as an endpoint. In the models relating it to the outcome, it was treated as a time-dependent covariate in the cox models. After completing standard anticoagulation treatment for 3 months with any anticoagulant, patients continuing anticoagulation were divided into two groups: standard therapeutic anticoagulation (any drug) vs those who transitioned to rivaroxaban 10 mg daily or apixaban 2.5mg twice daily any time after 3 months. Patients with recurrent VTE, major or CRNMB during the first 3 months were excluded from further analysis. Results: 219 patients (153 on Apixaban and 66 on Rivaroxaban) were identified in the low dose DOAC and 2521 in the standard anticoagulation group. The mean age was 60.7 years, mean weight was 93.2 Kg and 55.9% were males (Table 1). Patients on low dose DOACs were about the same age and weight compared to standard anticoagulation group. Among all diagnosis categories, patients with active cancer were less likely to be prescribed low dose DOACs (HR 0.56; 95%CI 0.42-0.73; P&lt;0.001), while low dose DOACs prescription was more likely in patients with pulmonary embolism (HR 1.45; 95%CI 1.11-1.89; P=0.007). The median months to start a low dose DOAC after completing the 3 months was 3.1 months with standard deviation of 6.6 months and interquartile range 2.8 months. There was no statistically significant association in the likelihood of going to a low dose group in relation to VTE recurrence (HR 1.36; 95%CI 0.42-4.45; P=0.61) or major bleeding (HR 0.59; 95%CI 0.08-4.37; P=0.61). However, transitioning to low dose DOAC was associated with reduced mortality (HR 0.53; 95%CI 0.35-0.80; P=0.003). Also, patients on low dose DOACs were more likely to have a CRNMB (HR 2.76; 95%CI 1.15-6.62; P=0.02). Conclusion: In this study of patients continuing anticoagulation past 3 months for an initial acute venous thromboembolic event, transitioning to low dose DOACs was not associated with any statistically significant association with VTE recurrence or major bleeding. However, mortality was lower and CRNMB was higher in this unadjusted analysis. Our results show that physicians are not always waiting until 6 months to transition to low doses and low doses are being utilized in cancer patients. Further research is needed to better understand the higher risk for CRNMB identified in this group. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.