Rates, management and outcome of bleeding complications during edoxaban therapy in daily care - results from the DRESDEN NOAC REGISTRY.

Edoxaban is licensed in many countries around the world, following successful phase-III trials in stroke prevention in atrial fibrillation (SPAF) and treatment of venous thromboembolism (VTE), but at present, little is known about edoxaban-related bleeding complications in daily care. Using data from a prospective, non-interventional oral anticoagulation registry, we analysed rates, management and outcome of edoxaban-related bleeding. Between 1 October 2011 and 28 February 2019, 996 patients were enrolled in the edoxaban cohort and a total of 891 bleeding events were observed (53.2% ISTH minor, 41.9% clinically relevant non-major and 4.9% major bleeding events). In case of major bleeding, surgical or interventional treatment was performed in 25.0% and prothrombin complex concentrate was given in 2 cases. In the time-to-first-event analysis, 100-patient-year rates of major bleeding were 3.1/100 patient-years (95% CI 2.2-4.2). In the as-exposed analysis, case-fatality rates of edoxaban-associated bleeding leading to hospitalizations were 7.5% and 9.0% at days 30 and 90 post bleeding, respectively. Taken together, our data indicate that, in real life, rates of edoxaban-related major bleeding in line with rates observed in phase III trials and that bleeding pattern, management and outcome of these events are not different from those reported for other direct factor Xa inhibitors. Clinical Trial Notation: Dresden NOAC Registry - ClinicalTrials.gov Identifier NCT01588119.

Management and outcome of gastrointestinal bleeding in patients taking oral anticoagulants or antiplatelet drugs.

BACKGROUND: Non-vitamin K dependent oral anticoagulants (NOACs) significantly decrease overall major bleeding rates compared with vitamin K antagonists (VKAs) but there is conflicting evidence regarding the relative risk of gastrointestinal bleeding. Since data regarding the types, the management, and the outcome of NOAC-associated gastrointestinal bleeding are scarce, we aimed to fill this gap by comparing cases of gastrointestinal bleeding associated with NOAC, VKA, or antiplatelet therapy. METHODS: All major gastrointestinal bleeding events documented in the prospective Dresden NOAC registry were identified, and bleeding location, lesion type, endoscopic treatment, use of blood and coagulation factor transfusion, length of stay, and in-hospital mortality were compared with historical data from a large cohort of consecutive gastrointestinal bleeding patients. RESULTS: In the 143 NOAC therapy cases, upper gastrointestinal tract bleeding was seen in 44.1%, lower gastrointestinal tract bleeding was seen in 42.0%, and no lesion could be identified in the remaining 14.0%. In contrast, upper gastrointestinal tract bleeding was commoner in the 185 VKA therapy cases (53.0%) and in the 711 antiplatelet therapy cases (68.1%). Among cases with upper gastrointestinal tract bleeding during VKA or antiplatelet therapy, 54.1% and 61.4% respectively presented with ulcers, compared with 27.0% for NOAC therapy. In contrast, hemorrhoid bleeding was the predominant lesion type for lower gastrointestinal tract bleeding with NOAC therapy, with a rate of 33.3%, compared with 10.6% with VKA therapy and 8.7% with antiplatelet therapy. NOAC-associated gastrointestinal bleeding resulted in comparatively low resource consumption, shorter hospitalization, and low in-hospital mortality (1.6%) compared with gastrointestinal bleeding historically seen with use of VKAs (in-hospital mortality 5.6%) or antiplatelet agents (in-hospital mortality 11.9%). CONCLUSIONS: Gastrointestinal bleeding in NOAC recipients is different from that seen with VKA or antiplatelet therapy and has a better short-term prognosis.

Drug persistence with rivaroxaban therapy in atrial fibrillation patients-results from the Dresden non-interventional oral anticoagulation registry.

AIMS: Worldwide, rivaroxaban is increasingly used for stroke prevention in atrial fibrillation (SPAF) but little is known about the rates of or reasons for rivaroxaban discontinuations in daily care. Using data from a prospective, non-interventional oral anticoagulation (NOAC) registry, we analysed rivaroxaban treatment persistence. METHODS AND RESULTS: Persistence with rivaroxaban in SPAF was assessed in an ongoing, prospective, non-interventional registry of >2600 NOAC patients from daily care using the Kaplan-Meier time-to-first-event analysis. Reasons for and management of rivaroxaban discontinuation were assessed. Potential baseline risk factors for treatment discontinuation were evaluated using Cox regression analysis. Between October 2011 and April 2014, 1204 rivaroxaban SPAF patients were enrolled [39.3% switched from vitamin K antagonists (VKAs) and 60.7% newly treated patients]. Of these, 223 patients (18.5%) stopped rivaroxaban during follow-up (median 544 days), which translates into a discontinuation rate of 13.6 (95% CI 11.8-15.4) per 100 patient-years. Most common reasons for treatment discontinuations were bleeding complications (30% of all discontinuations), followed by other side-effects (24.2%) and diagnosis of stable sinus rhythm (9.9%). A history of chronic heart failure (HR 1.43; 95% CI 1.09-1.87; P = 0.009) or diabetes (HR 1.39; 95% CI 1.06-1.82; P = 0.018) were the only statistically significant baseline risk factors for rivaroxaban discontinuation. After discontinuation of rivaroxaban, patients received antiplatelet therapy (31.8%), VKA (24.2%), another NOAC (18.4%), heparin (9.9%), or nothing (15.7%). CONCLUSION: Our data indicate that overall persistence with rivaroxaban therapy is high, with a discontinuation rate of ∼15% in the first year of treatment and few additional discontinuations thereafter.

Safety of switching from vitamin K antagonists to dabigatran or rivaroxaban in daily care--results from the Dresden NOAC registry.

AIM: Vitamin-K antagonists (VKA) and non-vitamin-K dependent oral anticoagulants (NOAC) have been approved for anticoagulation in venous thromboembolism (VTE) and atrial fibrillation and patients previously treated with VKA are switched to NOAC therapy. Safety data for this switching are urgently needed. METHODS: Using data from a large regional prospective registry of daily care NOAC patients, we evaluated the safety of switching anticoagulation from VKA to dabigatran or rivaroxaban. Switching procedures and cardiovascular and bleeding events occurring within 30 days after switching were centrally adjudicated. RESULTS: Between 1 October 2011 and 18 June 2013, 2231 patients were enrolled. Of these, 716 patients were switched from VKA to NOAC. Only 410 of the 546 evaluable patients (75.1%) had a recorded INR measurement within the 10 days preceding or following the end of VKA treatment (mean INR 2.4). As of day 30, major bleeding complications were rare (0.3%; 95% CI 0.0, 1.0) with an overall bleeding rate of 12.2% (95% CI 9.8, 14.8). Major cardiovascular events occurred in 0.8% (95% CI 0.3, 1.8). There was no significant difference in outcome event rates between the subgroups of patients with or without INR testing. CONCLUSION: In daily care, only 75% of VKA patients have an INR measurement documented before NOAC are started. On average, NOAC are started within 2 to 5 days after the last intake of VKA. However, at 30 days follow-up cardiovascular events or major bleedings were rare both in patients with and without INR testing. However, switching procedures need to be further evaluated in larger cohorts of patients.