Franziska Michalski

Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry

Worldwide, rivaroxaban is increasingly used for stroke prevention in atrial fibrillation and treatment of venous thromboembolism, but little is known about rivaroxaban-related bleeding complications in daily care. Using data from a prospective, noninterventional oral anticoagulation registry of daily care patients (Dresden NOAC registry), we analyzed rates, management, and outcome of rivaroxaban-related bleeding. Between October 1, 2011, and December 31, 2013, 1776 rivaroxaban patients were enrolled. So far, 762 patients (42.9%) reported 1082 bleeding events during/within 3 days after last intake of rivaroxaban (58.9% minor, 35.0% of nonmajor clinically relevant, and 6.1% major bleeding according to International Society on Thrombosis and Haemostasis definition). In case of major bleeding, surgical or interventional treatment was needed in 37.8% and prothrombin complex concentrate in 9.1%. In the time-to-first-event analysis, 100-patient-year rates of major bleeding were 3.1 (95% confidence interval 2.2-4.3) for stroke prevention in atrial fibrillation and 4.1 (95% confidence interval 2.5-6.4) for venous thromboembolism patients, respectively. In the as-treated analysis, case fatality rates of bleeding leading to hospitalizations were 5.1% and 6.3% at days 30 and 90 after bleeding, respectively. Our data indicate that, in real life, rates of rivaroxaban-related major bleeding may be lower and that the outcome may at least not be worse than that of major vitamin K antagonist bleeding, and probably better. This trial was registered at www.clinicaltrials.gov as identifier #NCT01588119.

Effectiveness and safety of rivaroxaban therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry.

The effectiveness and safety of rivaroxaban for stroke prevention in atrial fibrillation (SPAF) demonstrated in ROCKET AF needs to be confirmed in daily care. To evaluate effectiveness and safety of rivaroxaban therapy in SPAF patients in daily care, we used data from an ongoing, prospective, non-interventional registry of more than 2700 patients on novel oral anticoagulants in daily care. Between October 1, 2011 and February 28, 2013, a total of 1204 SPAF patients receiving rivaroxaban were enrolled. During a mean follow-up of 796.2 ± 207.3 days, the combined endpoint of stroke/transient ischaemic attack/systemic embolism occurred at a rate of 2.03/100 patient-years in the intention-to-treat analysis (95 % confidence interval [CI] 1.5-2.7) and at 1.7/100 patient-years in the on-treatment analysis (events within 3 days after last intake). On-treatment rates were higher in patients selected for 15 mg rivaroxaban (n=384) once daily [OD] compared with the 820 patients selected for 20 mg OD (2.7 [95 % CI 1.6-4.2] vs 1.25/100 patient-years [95 % CI 0.8-1.9]). On treatment, major bleeding occurred at a rate of 3.0/100 patient-years and significantly more often in patients receiving the 15 mg OD dose compared with the 20 mg OD dose (4.5 vs 2.4/100 patient-years). Rivaroxaban treatment discontinuation occurred in a total of 277 patients during follow-up (12.0/100 patient-years in Kaplan-Meier analysis). Our data contribute to the confirmation of effectiveness and relative safety of rivaroxaban in daily-care patients. Furthermore, rivaroxaban discontinuation rates were considerably lower than those reported for vitamin K antagonists.

Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation

The effectiveness and safety of dabigatran for stroke prevention in atrial fibrillation (SPAF) demonstrated in RE-LY needs to be confirmed in daily care. To evaluate treatment persistence, effectiveness and safety of dabigatran therapy in SPAF patients in daily care, we used data from an ongoing, prospective, non-interventional registry of more than 2,500 patients on novel oral anticoagulants in daily care. Between October 1, 2011 and February 28, 2013, a total of 341 SPAF patients receiving dabigatran were enrolled. The combined endpoint of stroke/transient ischaemic attack/systemic embolism occurred at a rate of 2.93/100 patient-years in the intention-to-treat analysis (95%-CI 1.6-4.9) and at 1.9/100 patient-years in the on treatment analysis (events within three days after last intake). On-treatment rates were higher in patients selected for 110 mg dabigatran (n=183) BID compared to the 158 patients selected for 150 mg BID (2.88 [95% CI 1.16- 5.93] vs 0.86/100 patient-years [95% CI 0.10, 3.12]). On treatment, major bleeding occurred at a rate of 2.3/100 patient-years and numerically more often in patients receiving the 110 mg BID dose compared to the 150 mg BID dose (2.9 vs 1.7/100 patient-years). Dabigatran treatment discontinuation occurred in a total of 124 patients during follow-up (25.8 per 100 patient-years in Kaplan Meier analysis). Main reasons for treatment discontinuation were non-bleeding side effects. Our data contribute to the confirmation of effectiveness and relative safety of dabigatran in unselected patients in daily care. However, discontinuation rates are not lower than those reported for patients treated with vitamin K antagonists.

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.

Management and outcomes of vaginal bleeding and heavy menstrual bleeding in women of reproductive age on direct oral anti-factor Xa inhibitor therapy: a case series

BACKGROUND Observational data and results from post-hoc analyses in clinical trials suggest that direct oral factor Xa inhibitors might increase menstrual bleeding intensity in women of reproductive age, but the extent of this effect is unknown. We aimed to investigate the management and outcomes of vaginal bleeding complications during therapy with direct oral factor Xa inhibitors in a case series of women of reproductive age. METHODS To identify individuals for inclusion in this case series, we searched two sources of prospectively collected data from women of reproductive age treated with direct oral factor Xa inhibitors: the non-interventional Dresden NOAC Registry (NCT01588119), which is based in the administrative district of Dresden (Saxony, Germany), and all locally archived data from phase 3 trials of direct oral factor Xa inhibitors done at University Hospital Carl Gustav Carus Dresden. Vaginal bleeding events were defined as any vaginal bleeding complications as reported by the patient. We collected data on type and dosage of anticoagulation; suspected or confirmed bleeding events, hospital admissions, and mortality; and pattern and management of vaginal bleeding events. For all cases of bleeding identified, we reviewed all available source data to identify examination results suggesting potential underlying anatomical causes of bleeding. FINDINGS We identified 178 women of reproductive age who received direct oral factor Xa inhibitor therapy, of whom 57 had vaginal bleeding events, including 50 who received rivaroxaban, six who received apixaban, and one who received edoxaban. These 57 women had 72 vaginal bleeding events, including 59 cases of heavy menstrual bleeding and 13 bleeding events unrelated to the menstrual cycle. 51 (86%) of these heavy menstrual bleeding events (two major bleeding events, 17 clinically relevant non-major bleeding events, 32 minor bleeding events) were treated conservatively (eg, change of oral hormone therapy or reduction, temporary interruption, or discontinuation of direct oral factor Xa inhibitor) and the remaining eight (14%) events (three major bleeding events and five clinically relevant non-major bleeding events) required elective surgical or interventional treatment (hysterectomy, curettage, ovary excision, or excision of ovarian cysts). Of the 57 women, 13 (23%) had a second bleeding event and two (4%) had a third event. Nine patients had underlying anatomical abnormalities; compared with patients without abnormalities, these patients had more intense bleeding, more had recurrent bleeding (five [56%] of nine patients with abnormalities vs eight [17%] of 48 patients without abnormalities), and more needed surgical treatment for bleeding (eight [89%] of nine vs zero of 48). INTERPRETATION Vaginal bleeding, particularly heavy menstrual bleeding, is a common complication in women of reproductive age on direct oral factor Xa inhibitor therapy. Most cases can be treated conservatively, but patients with severe or recurrent vaginal bleeding complications should be assessed for underlying anatomical abnormalities, which might require surgical or interventional treatment. Further data are needed to provide guidance on prevention and treatment of vaginal bleeding complications in this patient population. FUNDING None.

Vaginal bleeding and heavy menstrual bleeding during direct oral anti-Xa inhibitor therapy

Vaginal bleeding and heavy menstrual bleeding during direct oral anti-Xa inhibitor therapy -

Deep Vein Thrombosis – Current Management Strategies

Deep vein thrombosis (DVT) is a frequent and potentially life-threatening condition, and acute and late complications are common. The diagnostic approach to DVT needs to be reliable, widely available, and cost-effective. Furthermore, several therapeutic options are available for DVT treatment and the choice of anticoagulant drug, dosage, and treatment duration has to reflect the specific situation of the individual DVT patient. This review was aimed to provide bedside guidance for clinicians faced with common (and less common) clinical scenarios in DVT treatment.