Temporal trends in initiation of VKA, rivaroxaban, apixaban and dabigatran for the treatment of venous thromboembolism:A Danish nationwide cohort study

AbstractDanish nationwide registries were used to investigate temporal trends in initiation of rivaroxaban or apixaban or dabigatran versus vitamin K antagonists (VKA) in patients with venous thromboembolism (VTE). Patients treated with one of the NOACs (rivaroxaban, dabigatran, apixaban) or VKA were identified between February 2012 and September 2016. A total of 19,578 patients were included of which 10,844 (55.4%) were treated with VKA and 8,734 (44.6%) were treated with NOACs (rivaroxaban 7,572, apixaban 1,066, and dabigatran 96). Temporal trends showed a decrease in the initiation of VKA (p-value for decreasing trend, p &lt; 0001) and an increase in the initiation of rivaroxaban and apixaban (p-value for increasing trend, p &lt; 0001). By September 2016, 12%, 70%, 16%, and 2% of patients with VTE were initiated on VKA, rivaroxaban, apixaban, and dabigatran. Patients with previous VTE, chronic kidney disease, liver disease, cancer, and thrombophilia were more likely to be initiated on VKA compared with one of the NOACs. In conclusion the initiation of rivaroxaban and apixaban is increasing significantly over time in patients with VTE. Patients with previous VTE, chronic kidney disease, liver disease, cancer, and thrombophilia were more likely to be initiated on VKA compared with rivaroxaban or apixaban.</jats:p

Risk of ischemic stroke, hemorrhagic stroke, bleeding, and death in patients switching from vitamin K antagonist to dabigatran after an ablation

BACKGROUND:Safety regarding switching from vitamin K antagonist (VKA) to dabigatran therapy in post-ablation patients has never been investigated and safety data for this is urgently needed. The objective of this study was to examine if switch from VKA to dabigatran increased the risk of stroke, bleeding, and death in patients after ablation for atrial fibrillation. METHODS:Through the Danish nationwide registries, patients with non-valvular atrial fibrillation undergoing ablation were identified, in the period between August 22nd 2011 and December 31st 2015. The risk of ischemic stroke, hemorrhagic stroke, bleeding, and death, related to switching from VKA to dabigatran was examined using a multivariable Poisson regression model, where Incidence rate ratios (IRR) were estimated using VKA as reference. RESULTS:In total, 4,236 patients were included in the study cohort. The minority (n = 470, 11%) switched to dabigatran in the follow up period leaving the majority (n = 3,766, 89%) in VKA treatment. The patients in the dabigatran group were older, were more often males, and had higher CHA2DS2-VASc, and HAS-BLED scores. The incident rates of bleeding and death were almost twice as high in the dabigatran group compared with the VKA group. When adjusting for the individual components included in the CHA2DS2-VASc and HAS-BLED scores, the multivariable Poisson analyses yielded a non-significant IRR (95%CI) of 1.64 (0.72-3.75) for bleeding and of 1.41 (0.66-3.00) for death associated with the dabigatran group, compared to the VKA group. A significant increased risk of bleeding was found in the 110mg bid group with an IRR (95%CI) of 4.49(1.40-14.5). CONCLUSION:Shifting from VKA to dabigatran after ablation was associated with twice as high incidence of bleeding compared to the incidence in patients staying in VKA treatment. The only significant increased risk found in the adjusted analyses was for bleeding with 110mg bid dabigatran and not for 150mg bid. Since there was no dose-response for bleeding, the switch from VKA to dabigatran in itself was not a risk factor for bleeding

Familial clustering of venous thromboembolism:a Danish nationwide cohort study

BACKGROUND: Identification of risk factors for venous thromboembolism (VTE) is of utmost importance to improve current prophylactic regimes and treatment guidelines. The extent to which a family history contributes to the risk of VTE needs further exploration.OBJECTIVES: To examine the relative rate of VTE in first-degree relatives compared with the general population.METHODS: By crosslinking Danish nationwide registries we identified patients with VTE between 1978 and 2012, and their familial relations. The first member in a family to acquire VTE was defined as the proband. All first-degree relatives to probands were followed from the VTE date of the proband and until an event (VTE), death, emigration, 100 year birthday or end of study: 31st of December 2012, whichever came first. The relative rate of VTE was estimated by standardized incidence ratios (SIR) using time-dependent Poisson regression models, with the general population as a fixed reference.RESULTS: We identified 70,767 children of maternal probands, 66,065 children of paternal probands, and 29,183 siblings to sibling probands. Having a maternal proband or a paternal proband were associated with a significantly increased VTE rate of 2.15 (CI: 2.00-2.30) and 2.06 (CI: 1.92-2.21), respectively. The highest estimate of VTE was observed among siblings (adjusted SIR of 2.60 [CI: 2.38-2.83]). Noteworthy, the rate of VTE increased for all first-degree relatives when the proband was diagnosed with VTE in a young age (≤ 50 years).CONCLUSION: A family history of VTE was associated with a significantly increased rate of VTE among first-degree relatives compared with the general population.</p

Non-vitamin K antagonist oral anticoagulation usage according to age among patients with atrial fibrillation:Temporal trends 2011-2015 in Denmark

Among atrial fibrillation (AF) patients, Danish nationwide registries (2011–2015) were used to examine temporal trends of initiation patterns of oral anticoagulation (OAC) treatment according to age. Overall, 43,299 AF patients initiating vitamin K antagonists (VKA) (42%), dabigatran (29%), rivaroxaban (13%), or apixaban (16%) were included with mean age (SD) 72.1 (11.3), 71.5 (11.0), 74.3 (11.1), and 75.3 (11.1) years, respectively. Patients aged ≥85 years comprised 15%. Trend tests showed increase in patients ≥85 years initiating OAC (p < 0.0001). VKA usage decreased from 92% to 24% (p < 0.0001). This decrease was independent of age. Dabigatran was the most common non-VKA OAC (NOAC) (40% users), but usage decreased from 2014 until study end (6%) (p < 0.0001). Apixaban was the most used OAC at study end (41%), in particular among those ≥85 years (44%). Compared with patients aged <65 years, the odds ratios associated with initiating VKA, dabigatran, rivaroxaban, or apixaban for patients aged ≥85 years were 0.81 (95% CI 0.75–0.86), 0.65 (95% CI 0.60–0.70), 1.52 (95% CI 1.38–1.67), and 2.09 (95% CI 1.89–2.30), respectively. In conclusion, substantial increase in NOAC usage has occurred. Increasing age was associated with upstart of rivaroxaban or apixaban with reference to age <65 within the specific agent