Safety and Effectiveness of Apixaban in Japanese Patients With Venous Thromboembolism in Clinical Practice　- A Post-Marketing Surveillance.

BACKGROUND: A post-marketing surveillance study (STANDARD-VTE) evaluated the real-world safety and effectiveness of apixaban in Japanese patients prescribed for either the treatment of venous thromboembolism (VTE) or prevention of recurrent VTE.Methods and Results:Patients newly initiated on apixaban were followed up for 52 weeks or 28 days post-discontinuation. Subgroup analysis was performed on patients with and without active cancer, and on patients with provoked VTE and with unprovoked VTE. A total of 1,119 patients were enrolled. Of these, 43.1% were aged ≥75 years, 46.4% had body weight ≤60 kg, and 21.3% had active cancer; mean serum creatinine was 0.76 mg/dL. The incidence of adverse drug reactions (ADRs) was 8.85%, and that of severe ADRs was 3.22%. Incidence of any bleeding, major bleeding, and recurrent VTE was 6.70%, 3.40%, and 0.80%, respectively. In patients starting apixaban 10 mg twice daily, THE incidence of any bleeding and major bleeding was 7.72% and 3.86%, respectively. In patients with active cancer, THE incidence of any bleeding and major bleeding was 16.81% and 9.24%, respectively. CONCLUSIONS: No new safety signals of apixaban were identified in Japanese patients with VTE. In this study, the safety and effectiveness of apixaban in real-world practice was consistent with the results of the apixaban phase III trial.

Secondary stroke prevention with apixaban in nonvalvular atrial fibrillation: A subgroup analysis of the STANDARD study.

BACKGROUND: Data on independent risk factors for stroke recurrence in Japanese patients with nonvalvular atrial fibrillation are limited. METHODS: We performed a subgroup analysis of a postmarketing surveillance study of apixaban (STroke prevention ANticoagulant Drug Apixaban Real-world Data study) in Japanese patients with nonvalvular atrial fibrillation receiving oral apixaban (5 mg/2.5 mg twice daily) in routine clinical practice. Patients were categorized into primary and secondary prevention groups based on the absence or presence of a history of ischemic stroke/transient ischemic attack, respectively. RESULTS: Patients in the secondary prevention group (1101 of 6306 patients [17.5%] analyzed; mean observation period, 15.7 months) had a higher risk of ischemic stroke or hemorrhage than those in the primary prevention group. The incidence rates of major (3.92%/year vs 2.06%/year), intracranial (1.87%/year vs 0.55%/year), and cerebral (1.14%/year vs 0.37%/year) hemorrhage and effectiveness outcomes (ischemic stroke/systemic embolism/transient ischemic attack, 3.25%/year vs 0.57%/year) were significantly higher (all P < 0.001) in the secondary prevention group than in the primary prevention group. Multivariate analysis identified no independent risk factors in the secondary prevention group, while prior major bleeding, alcohol abuse, advanced age, male sex, lower body weight, higher serum creatinine, and antiplatelet drug use were identified as risk factors for major hemorrhage, and advanced age and antiplatelet drug use for effectiveness outcomes in the primary prevention group. CONCLUSIONS: Among Japanese patients with nonvalvular atrial fibrillation who received apixaban, presence of a history of ischemic stroke/transient ischemic attack was associated with higher incidence rates of hemorrhage and thromboembolic events.

Safety and effectiveness of reduced-dose apixaban in Japanese patients with nonvalvular atrial fibrillation in clinical practice: A sub-analysis of the STANDARD study.

BACKGROUND: The safety and effectiveness of reduced-dose apixaban 2.5mg twice daily (BID) have not been elucidated thoroughly in Japanese patients with nonvalvular atrial fibrillation (NVAF). METHODS: A post-marketing survey study included NVAF patients who newly initiated apixaban for prevention of thromboembolism, and followed them for 104 weeks. Apixaban doses were selected at the discretion of treating physicians. Hemorrhagic and thromboembolic (ischemic stroke, systemic embolism, and transient ischemic attack) events were examined. The relationship between dose reduction criteria (DRC), selected doses, and outcome events was also examined. RESULTS: Of 6306 patients, 3600 (57.1%) received the standard dose (5mg BID) and 2694 (42.7%) received the reduced dose. Compared with the standard-dose group, the reduced-dose group had more female patients; the patients were older, of lower body weight, with reduced creatinine clearance, higher thromboembolic and hemorrhagic risk scores, and more frequent antiplatelet use. Incidence rates of major hemorrhage and thromboembolism were higher in the reduced-dose group compared with the standard-dose group (3.00%/year vs 1.93%/year, p=0.001 and 1.40%/year vs 0.72%/year, p=0.001, respectively). In the standard-dose group, 90.0% of patients did not meet the DRC (recommended standard-dose group). In the reduced-dose group, 62.4% of patients met the DRC (recommended reduced-dose group) and 34.9% did not (non-recommended reduced-dose group). Incidence rates of major hemorrhage and thromboembolism were numerically highest in the recommended reduced-dose group (3.30%/year, p=0.007 and 1.69%/year, p<0.001, respectively), followed by the non-recommended reduced-dose group. In multivariate analysis, apixaban dose was not associated with these outcome events. CONCLUSION: The reduced-dose group showed higher incidence rates of thromboembolic and major hemorrhagic events than the standard-dose group due to baseline clinical characteristics. The safety and effectiveness of reduced-dose apixaban need to be carefully monitored in clinical practice.

Safety and effectiveness of apixaban in Japanese patients with nonvalvular atrial fibrillation in clinical practice: A regulatory postmarketing surveillance, the STANDARD study.

BACKGROUND: Apixaban, a non-vitamin K oral anticoagulant (NOAC), was approved in Japan in 2012 for the prevention of thromboembolic events in patients with nonvalvular atrial fibrillation (NVAF). However, the safety and effectiveness of apixaban in clinical practice have not yet been elucidated thoroughly among Japanese NVAF patients. METHODS: A postmarketing surveillance study was conducted to determine the safety and effectiveness of apixaban. Patients were followed-up for 104 weeks. Outcome events included adverse drug reactions (ADRs), hemorrhages, and thromboembolic events (ischemic stroke, systemic embolism [SE], and transient ischemic attack [TIA]). RESULTS: Among 6306 NVAF patients in the safety analysis set (age, 74.5 ± 10.1 years; women, 41.1%; and CHADS 2 score, 2.0 ± 1.4), 3600 patients (57.1%) received the standard dose (5 mg twice daily) and 2694 (42.7%) received a reduced dose (2.5 mg twice daily) of apixaban. ADRs occurred in 604 patients (9.58%), with the most common being epistaxis (0.86%), subcutaneous hemorrhage (0.67%), and hematuria (0.57%). Incidence rate of any hemorrhages and major hemorrhage was 5.52% per year and 2.36% per year, respectively. Incidence rate of ischemic stroke/SE/TIA was 1.00% per year among 6286 patients in the effectiveness analysis set. Among three subgroups (3106 apixaban initiators, 2038 patients switched from warfarin, and 1118 patients switched from other NOACs), incidence rates of major hemorrhage (P = 0.221 for trend) and ischemic stroke/SE/TIA (P = 0.686 for trend) were comparable. CONCLUSIONS: No new safety signals of apixaban were identified in Japanese NVAF patients. Safety and effectiveness of apixaban were consistent with those in the ARISTOTLE study.

Microwave spectroscopy of the PBr radical in the X (3)Sigma(-) state.

The microwave spectrum of the PBr radical in the X (3)Sigma(-) ground electronic state has been observed by a source modulated spectrometer. The PBr radical was generated in a free space cell by an acdc glow discharge in a mixture of PBr(3) with He andor H(2). A spectrum with three spin components for each of the two isotopomers, P(79)Br and P(81)Br, was observed. The spectrum showed hyperfine splitting caused by interactions due to both bromine and phosphorus nuclei. The molecular constants including the magnetic hyperfine and nuclear quadrupole hyperfine interaction constants were determined by analyzing the observed spectrum. The spin density of the unpaired electrons was estimated from the observed hyperfine coupling constants to be 85.4% and 16.3% on the phosphorus and bromine atoms, respectively.