What is the clinical evidence from this study?

Study design: RCT. Population: Total knee replacement (n=1217). Intervention: Apixaban vs. Enoxaparin 30 mg bid or open-label warfarin (INR 1.8-3.0). Primary outcome: Composite of all venous thromboembolic events (asymptomatic and symptomatic DVT, PE) and all-cause death during the treatment period (p=<0.02).

What does this research mean for the field?

Apixaban significantly reduces the composite of venous thromboembolic events and all-cause death compared to enoxaparin and warfarin after knee replacement surgery, while maintaining an acceptable bleeding safety profile. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To assess the antithrombotic efficacy, dose-response relationship, and bleeding safety of apixaban compared with enoxaparin and open-label warfarin in patients undergoing total knee replacement.

November 16, 2006Blood

A Phase II Randomized, Double-Blind, Eight-Arm, Parallel-Group, Dose-Response Study of Apixaban, a New Oral Factor Xa Inhibitor for the Prevention of Deep Vein Thrombosis in Knee Replacement Surgery - On Behalf of the Apixaban Investigators.

Q: What are the key findings of this study?

Apixaban significantly reduced the composite of VTE and all-cause death compared to enoxaparin (8.6% vs 15.6%; p<0.02) and warfarin (26.6%; p<0.001) after knee replacement surgery.

Q: What does this research mean for the field?

Apixaban significantly reduces the composite of venous thromboembolic events and all-cause death compared to enoxaparin and warfarin after knee replacement surgery, while maintaining an acceptable bleeding safety profile. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To assess the antithrombotic efficacy, dose-response relationship, and bleeding safety of apixaban compared with enoxaparin and open-label warfarin in patients undergoing total knee replacement.

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Key result

Apixaban significantly reduced the composite of VTE and all-cause death compared to enoxaparin (8.6% vs 15.6%; p<0.02) and warfarin (26.6%; p<0.001) after knee replacement surgery.

Why the study?

Does apixaban prevent venous thromboembolic events in patients undergoing total knee replacement?

Population

1,217 patients undergoing total knee replacement

Comparison

Apixaban given as a single or twice-daily… vs Enoxaparin 30 mg bid or open-label warfarin…

Design

RCT, allocated randomly to 1 of 6 double-blind doses of apixaban, or…

Follow-up

42 days

Authors

MLMichael R. LassenUniversity of Copenhagen BDBruce L. DavidsonVascular / Pulmonary Vascular AGAlexander GallusSouth Australia Pathology

Discussion

Member takes

Implication

Supports apixaban for VTE prophylaxis after knee replacement; extends Phase II data to guide Phase III trials.

Key Points

To assess the antithrombotic efficacy, dose-response relationship, and bleeding safety of apixaban compared with enoxaparin and open-label warfarin in patients undergoing total knee replacement.
Randomized, double-blind, 8-arm parallel-group phase II trial allocating patients undergoing knee replacement to 1 of 6 apixaban dosing regimens (5, 10, or 20 mg daily as single or divided doses), enoxaparin 30 mg twice daily, or open-label warfarin (INR 1.8–3.0).
Treatments lasted 10–14 days starting post-surgery, with follow-up on day 42 across 1,217 safety-analyzed and 856 efficacy-evaluable patients.
The primary endpoint was a composite of venous thromboembolism (symptomatic/asymptomatic deep vein thrombosis, pulmonary embolism) and all-cause death adjudicated by a blinded independent committee.
The combined apixaban group achieved a significantly lower composite VTE and all-cause death rate (8.6%) compared with enoxaparin (15.6%, p<0.02) and warfarin (26.6%, p<0.001).
Total daily apixaban doses of 5, 10, and 20 mg showed event rates of 10.6%, 8.6%, and 6.8% (dose-response trend p=0.09); apixaban 2.5 mg BID had a rate of 9.9% (95% CI: 5.1–17.0) and 5 mg QD had 11.3% (95% CI: 5.8–19.4) versus 15.6% (95% CI: 9.4–23.8) for enoxaparin.
Major bleeding across apixaban arms ranged from 0.0% (2.5 mg BID) to 3.3% (20 mg QD), with 0.0% major bleeding observed in both enoxaparin and warfarin groups.

Study Design

Type

RCT (n=1,217)

Blinding

Double-blind

Randomization

Parallel-Group

Structured PICO

Does apixaban prevent venous thromboembolic events in patients undergoing total knee replacement?

Population

1,217 patients undergoing total knee replacement

Intervention

Apixaban (5, 10, or 20 mg) given as a single or twice-daily divided dose, started 12 to 24 hours after completing surgery, continued for 10-14 days

Comparator

Enoxaparin 30 mg bid (started 12 to 24 hours after completing surgery) or open-label warfarin titrated to an INR of 1.8-3.0 (started the evening of the day of surgery)

Outcome

Composite of all venous thromboembolic events (VTE) comprising asymptomatic and symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE) and all-cause death during the treatment periodcomposite

Main Result

Absolute Event Rate: 8.6% vs 15.6%

p-value: p=<0.02

In a Phase II dose-ranging study, apixaban demonstrated superior efficacy for VTE prevention after knee replacement surgery compared to enoxaparin and warfarin, with an acceptable bleeding profile.

Cite This Study

Lassen et al. (2006) conducted an RCT in Total knee replacement (n=1,217). Apixaban vs. Enoxaparin 30 mg bid or open-label warfarin (INR 1.8-3.0) was evaluated on Composite of all venous thromboembolic events (asymptomatic and symptomatic DVT, PE) and all-cause death during the treatment period (p=<0.02). Apixaban significantly reduced the composite of VTE and all-cause death compared to enoxaparin (8.6% vs 15.6%; p<0.02) and warfarin (26.6%; p<0.001) after knee replacement surgery.

synapsesocial.com/papers/6a1553b09b87f33fc69f73ad https://doi.org/10.1182/blood.v108.11.574.574

Topics

PCSK9 inhibitors

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A Phase II Randomized, Double-Blind, Eight-Arm, Parallel-Group, Dose-Response Study of Apixaban, a New Oral Factor Xa Inhibitor for the Prevention of Deep Vein Thrombosis in Knee Replacement Surgery - On Behalf of the Apixaban Investigators.

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Cite This Study

Topics

A Phase II Randomized, Double-Blind, Eight-Arm, Parallel-Group, Dose-Response Study of Apixaban, a New Oral Factor Xa Inhibitor for the Prevention of Deep Vein Thrombosis in Knee Replacement Surgery - On Behalf of the Apixaban Investigators.

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Cite This Study

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