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LBA-1 Two Doses of Apixaban for the Extended Treatment of Venous Thromboembolism

Program: Late-breaking Abstracts
Session: Late-Breaking Abstracts
Tuesday, December 11, 2012, 7:30 AM-9:00 AM
Hall B5, Level 1, Building B (Georgia World Congress Center)

Giancarlo Agnelli, MD1*, Harry Roger Buller, MD, PhD2*, Alexander Cohen, MD3*, Madelyn Curto, DVM4*, Alexander S. Gallus, M.D.5, Margot R. Johnson, MD, BSC4*, Anthony R. Porcari, PhD, PharmD4, Gary E Raskob, PhD6 and Jeffrey I. Weitz, MD7

1University of Perugia, Perugia, Italy
2Dept of Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands
3King’s College Hospital, London, London, United Kingdom
4Pfizer Inc,, Groton, CT
5SA Pathology, Flinders Medical Centre, Bedford Park, Australia
6College of Public Health, Univesity of Oklahoma Health Sciences Center, Oklahoma City, OK
7Thrombosis & Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada

Background: Apixaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for extended treatment of venous thromboembolism.

Objectives: To compare the efficacy and safety of two doses of apixaban (2.5 or 5 mg twice daily) with placebo for the extended treatment of venous thromboembolism in patients who have completed 6 to 12 months of prior anticoagulant therapy.

Methods: This randomized, double-blind study (ClinicalTrials.gov number, NCT00633893) compared two apixaban doses (2.5 or 5 mg twice daily) with placebo for 12 months in patients with venous thromboembolism who had completed 6–12 months of anticoagulation. The primary efficacy outcome was symptomatic recurrent venous thromboembolism or all-cause mortality. Secondary efficacy outcomes included (a) the composite of symptomatic venous thromboembolism or venous thromboembolism-related death, and (b) the composite of symptomatic venous thromboembolism, venous thromboembolism-related death, myocardial infarction, stroke, or cardiovascular-related death. The primary safety outcome was major bleeding; the secondary safety outcome was major and clinically relevant non-major bleeding.

Results: The study included 2486 patients: 829, 840, and 815 randomized to placebo, apixaban 2.5 mg, and apixaban 5 mg, respectively. Rates of the primary efficacy outcome were 11.6% in the placebo group, compared with 3.8% and 4.2% in the apixaban 2.5 mg and 5 mg groups, respectively (absolute risk differences of 7.8% and  7.4%, respectively; 95% confidence intervals 5.3% to 10.3% and 4.8% to 10%, respectively; p<0.001 for both comparisons). Other outcomes are detailed in the Table.

Conclusions: Both doses of apixaban reduced the risk of symptomatic recurrent fatal or non-fatal venous thromboembolism by approximately 80% without increasing the rate of major bleeding. In addition, both apixaban doses reduced arterial thrombotic events. The lower apixaban dose may be preferred for extended treatment, because of the trend for less clinically relevant non-major bleeding.


Apixaban
2.5 mg

Apixaban
5 mg

Placebo

Apixaban 2.5 mg vs. Placebo

Apixaban 5 mg vs. Placebo

Apixaban 2.5 mg vs. 5 mg

No. patients (%)

No. patients (%)

No. patients (%)

Relative Risk

(95% CI)

Relative Risk

(95% CI)

Relative Risk

(95% CI)

Intent-to-treat population

840

813

829

First recurrent VTE or VTE-related death

14 (1.7)

14 (1.7)

73 (8.8)

0.19 (0.11 to 0.33)

0.20 (0.11 to 0.34)

0.97 (0.46 to 2.02)

First recurrent VTE, VTE-related death, MI, stroke, or CV-related death

18 (2.1)

19 (2.3)

83 (10.0)

0.21 (0.13 to 0.35)

0.23 (0.14 to 0.38)

0.92 (0.48 to 1.74)

Safety population

840

811

826

First major bleed

2 (0.2)

1 (0.1)

4 (0.5)

0.49 (0.09 to 2.64)

0.25 (0.03 to 2.24)

1.93 (0.18 to 21.25)

First clinically relevant non-major bleed

25 (3.0)

34 (4.2)

19 (2.3)

1.29 (0.72 to 2.33)

1.82 (1.05 to 3.18)

0.71 (0.43 to 1.18)

First major or clinically relevant non-major bleeding

27 (3.2)

35 (4.3)

22 (2.7)

1.20 (0.69 to 2.10)

1.62 (0.96 to 2.73)

0.74 (0.46 to 1.22)

Net clinical benefit: First VTE, VTE-related death, MI, stroke, CV-related death or major bleeding

20 (2.4)

20 (2.5)

86 (10.4)

0.23 (0.14 to 0.37)

0.24 (0.15 to 0.38)

0.97 (0.52 to 1.79)


Disclosures: Agnelli: Bristol Myers Squibb: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy; Boehringer Ingelheim: Consultancy; Bayer Healthcare: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Sanofi-Aventis : Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Buller: Isis: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Sanofi-aventis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Daiichi: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Thrombogenics: Consultancy, Research Funding. Cohen: Astellas: Consultancy, Research Funding; AstraZenica: Consultancy, Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Boheringer-Ingelheim: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Daiichi: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; GlaxoSmithKline: Consultancy, Research Funding; Johnson & Johnson: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Mitsubishi Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Portola: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Schering Plough: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Curto: Pfizer: Employment. Gallus: Pfizer: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Daiichi Sankyo: Consultancy; Bayer: Membership on an entity’s Board of Directors or advisory committees; boehringer-Ingelheim: Membership on an entity’s Board of Directors or advisory committees. Johnson: Pfizer: Employment. Porcari: Pfizer: Employment. Raskob: Pfizer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Bristol Myer Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Johnson & Johnson: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy; Quintiles: Consultancy; National Blood Clot Alliance: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Weitz: Bristol Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Daiichi-Sankyo: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy, Honoraria.

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