Key Points• In a real-world setting, annualized bleeding rates of major rivaroxaban bleeding are lower than those reported for vitamin K antagonists.• Treatment of major rivaroxaban bleeding is simple and rarely requires pro-coagulants; outcome at 90 days is better than that reported for vitamin K antagonists.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-patientyear 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. (Blood. 2014;124(6):955-962)

AimsWorldwide, 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 resultsPersistence 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%).ConclusionOur 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.

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И.С. ЯВЕЛОВ, д.м.н., ФГБУ «Федеральный научно-клинический центр физико-химической медицины Федерального медико-биологического агентства» В статье представлены результаты применения ривароксабана для профилактики инсульта и тромбоэмболий не в сосуды центральной нервной системы у больных с неклапанной фибрилляцией предсердий в широкой врачебной практике. Показано, что в целом эффективность и безопасность этого лекарственного средства в повсед-невной врачебной деятельности соответствует ожиданиям, сформировавшихся по итогам крупного контролируемого клинического испытания ROCKET-AF.КЛЮЧЕВЫЕ СЛОВА: пероральные антикоагулянты, фибрилляция предсердий, ROCRET-AF, ривароксабан

AIMVitamin-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. METHODSUsing 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. RESULTSBetween 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. CONCLUSIONIn 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. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Patients on vitamin-K antagonists (VKA) need to have their INR tested before a transition to a different anticoagulant. Different INR thresholds exist for different anticoagulants and for different indications, but existing recommendations have never been analyzed. • Consequently, the recommendations for switching from VKA to non-vitamin-K dependent direct oral anticoagulants (NOAC or DOAC) in the summary of product characteristics (SMPCs) of the NOACs are not evidence based.• In daily practice, considerable concerns are raised about these recommendations (initiation of NOAC at INR values <2.0 for apixaban and dabigatran in SPAF, INR <2.5 for rivaroxaban in venous thromboembolism (VTE) and INR <3.0 for rivaroxaban in stroke prevention in non-valvular atrial fibrillation (SPAF).• In the Rocket-AF trial, major bleeding complications were highest in the subgroup of rivaroxaban patients with VKA pre-treatment compared with the subgroups of patients without VKA pre-treatment or the subgroup of pre-treated patients randomized to warfarin. This could be an indicator that the transition from VKA pre-treatment to NOAC increases bleeding risks. WHAT THIS STUDY ADDS• In daily practice, only 75% of all patients had a recorded INR measurement within 10 days before or after the end of VKA treatment. The baseline characteristics of patients receiving INR testing were not different ...

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Gastrointestinal bleeding in NOAC recipients is different from that seen with VKA or antiplatelet therapy and has a better short-term prognosis.

Prospective trials have shown that rivaroxaban thromboprophylaxis is superior over low-molecular-weight heparin (LMWH) in patients undergoing hip and knee replacement surgery. However, patients treated under trial conditions are different from unselected routine patients, which may affect efficacy and safety of thromboprophylaxis. The objective was to evaluate the efficacy and safety of rivaroxaban or LMWH thromboprophylaxis in unselected patients undergoing hip and knee replacement surgery in daily care. In a monocentric, retrospective cohort study in 5,061 consecutive patients undergoing hip and knee replacement surgery a comparison of LMWH (hospital standard in 2006-2007) and rivaroxaban (since 2009) was made with regard to rates of symptomatic VTE, bleeding and surgical complications and length of hospital stay. Rates of symptomatic VTE were 4.1 % (LMWH) and 2.1 % (rivaroxaban; p=0.005) with rates for distal DVT 2.5 vs. 1.1 % (p<0.001). Rates of major VTE were numerically higher with LMWH (1.7 vs. 1.1%, not statistically significant). Rates of major bleeding (overt bleeding leading to surgical revision or death, occurring in a critical site, or transfusion of at least two units of packed red blood cells) were statistically lower with rivaroxaban (2.9 vs. 7.0%; p<0.001). Rivaroxaban patients had fewer surgical complications (1.1 vs. 3.7%; p<0.001) and a shorter length of hospitalisation (8.3 days; 95% CI 8.1- 8.5 vs. 11.1 days; 10.7- 11.5; p< 0.001). We conclude that rivaroxaban thromboprophylaxis is more effective than LMWH in unselected patients undergoing hip and knee replacement surgery in daily care and that switching from LMWH to rivaroxaban could be beneficial. Prospective comparisons are warranted to confirm our findings.