Apixaban for the Treatment of Japanese Subjects With Acute Venous Thromboembolism (AMPLIFY-J Study).

Abstract

BACKGROUND:

Anticoagulation is recommended as standard of care for venous thromboembolism (VTE) (pulmonary embolism [PE]/deep vein thrombosis [DVT]), for which unfractionated heparin (UFH) and warfarin are used in Japan. In the multi-regional AMPLIFY study, a fixed-dose regimen of apixaban alone was non-inferior to conventional therapy for treatment of PE/DVT and was associated with significantly fewer bleeding events.

METHODS AND RESULTS:

Japan phase 3 study (AMPLIFY-J), randomized, active-controlled, open-label study in Japanese subjects with acute PE/DVT, was designed based on AMPLIFY. Key objectives were to investigate safety and efficacy of apixaban in symptomatic PE/DVT subjects during 24-week treatment. UFH/warfarin was used as control treatment. Apixaban was initiated at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 23 weeks. All endpoints and imaging for thrombotic burden were assessed by an event adjudication committee. Eighty subjects were randomized, 33 subjects (41.3%) were aged <65 years. Proportion of major/clinically relevant non-major bleeding was lower in apixaban (7.5%) compared with well-controlled UFH/warfarin (28.2%; median TTR, 70.4%). [corrected]. Recurrent VTE occurred in no subjects in apixaban and in 1 subject in UFH/warfarin. Thrombotic burden results were similar in both groups. Proportions of subjects with adverse events was generally similar in both groups.

CONCLUSIONS:

Apixaban was well-tolerated and had a favorable safety profile. No clinically important efficacy difference compared with UFH/warfarin was observed.

• Authors: Mashio Nakamura, Masakatsu Nishikawa, Issei Komuro, Isao Kitajima, Yoshio Uetsuka, Takuji Yamagami, Hiroki Minamiguchi, Rika Yoshimatsu, Kosuke Tanabe, Nobushige Matsuoka, Kazuhiro Kanmuri, Hisao Ogawa
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 79 Issue 6 Pg. 1230-6 ( 2015) ISSN: 1347-4820 [Electronic] Japan
• PMID: 25912695 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Factor Xa Inhibitors
• Pyrazoles
• Pyridones
• apixaban
• Warfarin
• Heparin

Topics

• Aged
• Aged, 80 and over
• Anticoagulants (adverse effects, therapeutic use)
• Factor Xa Inhibitors (adverse effects, therapeutic use)
• Female
• Hemorrhage (chemically induced)
• Heparin (adverse effects, therapeutic use)
• Humans
• International Normalized Ratio
• Japan
• Male
• Middle Aged
• Pulmonary Embolism (drug therapy)
• Pyrazoles (adverse effects, therapeutic use)
• Pyridones (adverse effects, therapeutic use)
• Recurrence
• Treatment Outcome
• Venous Thromboembolism (drug therapy)
• Venous Thrombosis (drug therapy)
• Warfarin (adverse effects, therapeutic use)