Apixaban to prevent venous thromboembolism in patients with cancer

AVERT Investigators

doi:10.1056/NEJMoa1814468

Apixaban to prevent venous thromboembolism in patients with cancer

AVERT Investigators

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

680 Citas (Scopus)

Resumen

BACKGROUND: Patients with active cancer have an increased risk of venous thromboembolism, which results in substantial morbidity, mortality, and health care expenditures. The Khorana score (range, 0 to 6, with higher scores indicating a higher risk of venous thromboembolism) has been validated to identify patients with cancer at elevated risk for this complication and may help select those who could benefit from thromboprophylaxis. METHODS: We conducted a randomized, placebo-controlled, double-blind clinical trial assessing the efficacy and safety of apixaban (2.5 mg twice daily) for thromboprophylaxis in ambulatory patients with cancer who were at intermediate-to-high risk for venous thromboembolism (Khorana score, ≥2) and were initiating chemotherapy. The primary efficacy outcome was objectively documented venous thromboembolism over a follow-up period of 180 days. The main safety outcome was a major bleeding episode. RESULTS: Of the 574 patients who underwent randomization, 563 were included in the modified intention-to-treat analysis. Venous thromboembolism occurred in 12 of 288 patients (4.2%) in the apixaban group and in 28 of 275 patients (10.2%) in the placebo group (hazard ratio, 0.41; 95% confidence interval [CI], 0.26 to 0.65; P<0.001). In the modified intention-to-treat analysis, major bleeding occurred in 10 patients (3.5%) in the apixaban group and in 5 patients (1.8%) in the placebo group (hazard ratio, 2.00; 95% CI, 1.01 to 3.95; P=0.046). During the treatment period, major bleeding occurred in 6 patients (2.1%) in the apixaban group and in 3 patients (1.1%) in the placebo group (hazard ratio, 1.89; 95% CI, 0.39 to 9.24). CONCLUSIONS: Apixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo.

Idioma original	English
Páginas (desde-hasta)	711-719
Número de páginas	9
Publicación	New England Journal of Medicine
Volumen	380
N.º	8
DOI	https://doi.org/10.1056/NEJMoa1814468
Estado	Published - feb. 21 2019
Publicado de forma externa	Sí

Nota bibliográfica

Funding Information:
Apixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo. (Funded by the Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance; AVERT ClinicalTrials.gov number, NCT02048865.)

Funding Information:
Dr. Carrier reports receiving grant support and honoraria from Leo Pharma and Bayer and honoraria from Sanofi-Aventis, Pfizer, and Bristol-Myers Squibb; Dr. Abou-Nassar, receiving honoraria from Janssen, Sanofi, Lundbeck, Novartis, Celgene, and Leo Pharma; Dr. Tagalakis, receiving honoraria from Bristol-Myers Squibb, Pfizer, and Leo Pharma, fees for serving on a speakers bureau from Servier, grant support from Sanofi and CanVECTOR–Canadian Institutes of Health Research, and travel support from Bayer; Dr. Shivakumar, receiving lecture fees from Pfizer and Bayer; Dr. Kuruvilla, receiving lecture fees and advisory board fees from Pfizer, Leo Pharma, Bayer, and Servier; Dr. Hill, receiving consulting fees and honoraria from Bayer and honoraria from Boehringer Ingelheim, Leo Pharma, Bristol-Myers Squibb, and Pfizer; Dr. Lee, receiving grant support from Bristol-Myers Squibb, consulting fees and fees for serving on a steering committee from Bayer, and consulting fees from Leo Pharma, Pfizer, and Servier; Dr. Gross, receiving lecture fees and advisory board fees from Bristol-Myers Squibb, Pfizer, Bayer, and Leo Pharma, receiving advisory board fees from ApoPharma, and holding a patent (CA2014/000483) on a method for assaying a protease; Dr. El-Maraghi, receiving honoraria from Amgen, Bayer, Bristol-Myers Squibb, Celgene, Eli Lilly, Ipsen, Leo Pharma, Merck, Pfizer, Servier, and Takeda and honoraria and travel support from AstraZeneca, Boehringer Ingelheim, and Roche; Dr. Goss, receiving honoraria from AstraZeneca and Boehringer Ingelheim; Dr. Le Gal, receiving honoraria from Sanofi and bioMérieux and serving as coinvestigator for Portola Pharmaceuticals, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, Leo Pharma, Daiichi Sankyo, and Bayer; Dr. Stewart, receiving honoraria from Roche Canada, Boehringer Ingelheim Canada, Novartis Canada, Merck Canada, AstraZeneca Canada, Bristol-Myers Squibb, Exactis, Pfizer Canada, and Celgene; and Dr. Wells, receiving grant support, lecture fees, and advisory board fees from Bayer HealthCare, lecture fees from Medscape, Pfizer, and Daiichi Sankyo, fees for serving on a writing committee from Itreas, grant support from Bristol-Myers Squibb/Pfizer, consulting fees from Janssen Scientific, and fees for serving on a roundtable from Sanofi. No other potential conflict of interest relevant to this article was reported.

Publisher Copyright:
Copyright © 2018 Massachusetts Medical Society.

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General Medicine

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@article{38e25ae75a5042dba95ad21bda44f15f,

title = "Apixaban to prevent venous thromboembolism in patients with cancer",

abstract = "BACKGROUND: Patients with active cancer have an increased risk of venous thromboembolism, which results in substantial morbidity, mortality, and health care expenditures. The Khorana score (range, 0 to 6, with higher scores indicating a higher risk of venous thromboembolism) has been validated to identify patients with cancer at elevated risk for this complication and may help select those who could benefit from thromboprophylaxis. METHODS: We conducted a randomized, placebo-controlled, double-blind clinical trial assessing the efficacy and safety of apixaban (2.5 mg twice daily) for thromboprophylaxis in ambulatory patients with cancer who were at intermediate-to-high risk for venous thromboembolism (Khorana score, ≥2) and were initiating chemotherapy. The primary efficacy outcome was objectively documented venous thromboembolism over a follow-up period of 180 days. The main safety outcome was a major bleeding episode. RESULTS: Of the 574 patients who underwent randomization, 563 were included in the modified intention-to-treat analysis. Venous thromboembolism occurred in 12 of 288 patients (4.2%) in the apixaban group and in 28 of 275 patients (10.2%) in the placebo group (hazard ratio, 0.41; 95% confidence interval [CI], 0.26 to 0.65; P<0.001). In the modified intention-to-treat analysis, major bleeding occurred in 10 patients (3.5%) in the apixaban group and in 5 patients (1.8%) in the placebo group (hazard ratio, 2.00; 95% CI, 1.01 to 3.95; P=0.046). During the treatment period, major bleeding occurred in 6 patients (2.1%) in the apixaban group and in 3 patients (1.1%) in the placebo group (hazard ratio, 1.89; 95% CI, 0.39 to 9.24). CONCLUSIONS: Apixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo.",

author = "{AVERT Investigators} and Marc Carrier and Karim Abou-Nassar and Ranjeeta Mallick and Vicky Tagalakis and Sudeep Shivakumar and Ariah Schattner and Philip Kuruvilla and Danny Hill and Silvana Spadafora and Katerine Marquis and Mateya Trinkaus and Anna Tomiak and Lee, {Agnes Y.Y.} and Gross, {Peter L.} and Alejandro Lazo-Langner and Robert El-Maraghi and Glenwood Goss and Gal, {Gregoire Le} and David Stewart and Timothy Ramsay and Marc Rodger and Debra Witham and Wells, {Philip S.}",

note = "Funding Information: Apixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo. (Funded by the Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance; AVERT ClinicalTrials.gov number, NCT02048865.) Funding Information: Dr. Carrier reports receiving grant support and honoraria from Leo Pharma and Bayer and honoraria from Sanofi-Aventis, Pfizer, and Bristol-Myers Squibb; Dr. Abou-Nassar, receiving honoraria from Janssen, Sanofi, Lundbeck, Novartis, Celgene, and Leo Pharma; Dr. Tagalakis, receiving honoraria from Bristol-Myers Squibb, Pfizer, and Leo Pharma, fees for serving on a speakers bureau from Servier, grant support from Sanofi and CanVECTOR–Canadian Institutes of Health Research, and travel support from Bayer; Dr. Shivakumar, receiving lecture fees from Pfizer and Bayer; Dr. Kuruvilla, receiving lecture fees and advisory board fees from Pfizer, Leo Pharma, Bayer, and Servier; Dr. Hill, receiving consulting fees and honoraria from Bayer and honoraria from Boehringer Ingelheim, Leo Pharma, Bristol-Myers Squibb, and Pfizer; Dr. Lee, receiving grant support from Bristol-Myers Squibb, consulting fees and fees for serving on a steering committee from Bayer, and consulting fees from Leo Pharma, Pfizer, and Servier; Dr. Gross, receiving lecture fees and advisory board fees from Bristol-Myers Squibb, Pfizer, Bayer, and Leo Pharma, receiving advisory board fees from ApoPharma, and holding a patent (CA2014/000483) on a method for assaying a protease; Dr. El-Maraghi, receiving honoraria from Amgen, Bayer, Bristol-Myers Squibb, Celgene, Eli Lilly, Ipsen, Leo Pharma, Merck, Pfizer, Servier, and Takeda and honoraria and travel support from AstraZeneca, Boehringer Ingelheim, and Roche; Dr. Goss, receiving honoraria from AstraZeneca and Boehringer Ingelheim; Dr. Le Gal, receiving honoraria from Sanofi and bioM{\'e}rieux and serving as coinvestigator for Portola Pharmaceuticals, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, Leo Pharma, Daiichi Sankyo, and Bayer; Dr. Stewart, receiving honoraria from Roche Canada, Boehringer Ingelheim Canada, Novartis Canada, Merck Canada, AstraZeneca Canada, Bristol-Myers Squibb, Exactis, Pfizer Canada, and Celgene; and Dr. Wells, receiving grant support, lecture fees, and advisory board fees from Bayer HealthCare, lecture fees from Medscape, Pfizer, and Daiichi Sankyo, fees for serving on a writing committee from Itreas, grant support from Bristol-Myers Squibb/Pfizer, consulting fees from Janssen Scientific, and fees for serving on a roundtable from Sanofi. No other potential conflict of interest relevant to this article was reported. Publisher Copyright: Copyright {\textcopyright} 2018 Massachusetts Medical Society.",

year = "2019",

month = feb,

day = "21",

doi = "10.1056/NEJMoa1814468",

language = "English",

volume = "380",

pages = "711--719",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "8",

}

TY - JOUR

T1 - Apixaban to prevent venous thromboembolism in patients with cancer

AU - AVERT Investigators

AU - Carrier, Marc

AU - Abou-Nassar, Karim

AU - Mallick, Ranjeeta

AU - Tagalakis, Vicky

AU - Shivakumar, Sudeep

AU - Schattner, Ariah

AU - Kuruvilla, Philip

AU - Hill, Danny

AU - Spadafora, Silvana

AU - Marquis, Katerine

AU - Trinkaus, Mateya

AU - Tomiak, Anna

AU - Lee, Agnes Y.Y.

AU - Gross, Peter L.

AU - Lazo-Langner, Alejandro

AU - El-Maraghi, Robert

AU - Goss, Glenwood

AU - Gal, Gregoire Le

AU - Stewart, David

AU - Ramsay, Timothy

AU - Rodger, Marc

AU - Witham, Debra

AU - Wells, Philip S.

N1 - Funding Information: Apixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo. (Funded by the Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance; AVERT ClinicalTrials.gov number, NCT02048865.) Funding Information: Dr. Carrier reports receiving grant support and honoraria from Leo Pharma and Bayer and honoraria from Sanofi-Aventis, Pfizer, and Bristol-Myers Squibb; Dr. Abou-Nassar, receiving honoraria from Janssen, Sanofi, Lundbeck, Novartis, Celgene, and Leo Pharma; Dr. Tagalakis, receiving honoraria from Bristol-Myers Squibb, Pfizer, and Leo Pharma, fees for serving on a speakers bureau from Servier, grant support from Sanofi and CanVECTOR–Canadian Institutes of Health Research, and travel support from Bayer; Dr. Shivakumar, receiving lecture fees from Pfizer and Bayer; Dr. Kuruvilla, receiving lecture fees and advisory board fees from Pfizer, Leo Pharma, Bayer, and Servier; Dr. Hill, receiving consulting fees and honoraria from Bayer and honoraria from Boehringer Ingelheim, Leo Pharma, Bristol-Myers Squibb, and Pfizer; Dr. Lee, receiving grant support from Bristol-Myers Squibb, consulting fees and fees for serving on a steering committee from Bayer, and consulting fees from Leo Pharma, Pfizer, and Servier; Dr. Gross, receiving lecture fees and advisory board fees from Bristol-Myers Squibb, Pfizer, Bayer, and Leo Pharma, receiving advisory board fees from ApoPharma, and holding a patent (CA2014/000483) on a method for assaying a protease; Dr. El-Maraghi, receiving honoraria from Amgen, Bayer, Bristol-Myers Squibb, Celgene, Eli Lilly, Ipsen, Leo Pharma, Merck, Pfizer, Servier, and Takeda and honoraria and travel support from AstraZeneca, Boehringer Ingelheim, and Roche; Dr. Goss, receiving honoraria from AstraZeneca and Boehringer Ingelheim; Dr. Le Gal, receiving honoraria from Sanofi and bioMérieux and serving as coinvestigator for Portola Pharmaceuticals, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, Leo Pharma, Daiichi Sankyo, and Bayer; Dr. Stewart, receiving honoraria from Roche Canada, Boehringer Ingelheim Canada, Novartis Canada, Merck Canada, AstraZeneca Canada, Bristol-Myers Squibb, Exactis, Pfizer Canada, and Celgene; and Dr. Wells, receiving grant support, lecture fees, and advisory board fees from Bayer HealthCare, lecture fees from Medscape, Pfizer, and Daiichi Sankyo, fees for serving on a writing committee from Itreas, grant support from Bristol-Myers Squibb/Pfizer, consulting fees from Janssen Scientific, and fees for serving on a roundtable from Sanofi. No other potential conflict of interest relevant to this article was reported. Publisher Copyright: Copyright © 2018 Massachusetts Medical Society.

PY - 2019/2/21

Y1 - 2019/2/21

N2 - BACKGROUND: Patients with active cancer have an increased risk of venous thromboembolism, which results in substantial morbidity, mortality, and health care expenditures. The Khorana score (range, 0 to 6, with higher scores indicating a higher risk of venous thromboembolism) has been validated to identify patients with cancer at elevated risk for this complication and may help select those who could benefit from thromboprophylaxis. METHODS: We conducted a randomized, placebo-controlled, double-blind clinical trial assessing the efficacy and safety of apixaban (2.5 mg twice daily) for thromboprophylaxis in ambulatory patients with cancer who were at intermediate-to-high risk for venous thromboembolism (Khorana score, ≥2) and were initiating chemotherapy. The primary efficacy outcome was objectively documented venous thromboembolism over a follow-up period of 180 days. The main safety outcome was a major bleeding episode. RESULTS: Of the 574 patients who underwent randomization, 563 were included in the modified intention-to-treat analysis. Venous thromboembolism occurred in 12 of 288 patients (4.2%) in the apixaban group and in 28 of 275 patients (10.2%) in the placebo group (hazard ratio, 0.41; 95% confidence interval [CI], 0.26 to 0.65; P<0.001). In the modified intention-to-treat analysis, major bleeding occurred in 10 patients (3.5%) in the apixaban group and in 5 patients (1.8%) in the placebo group (hazard ratio, 2.00; 95% CI, 1.01 to 3.95; P=0.046). During the treatment period, major bleeding occurred in 6 patients (2.1%) in the apixaban group and in 3 patients (1.1%) in the placebo group (hazard ratio, 1.89; 95% CI, 0.39 to 9.24). CONCLUSIONS: Apixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo.

AB - BACKGROUND: Patients with active cancer have an increased risk of venous thromboembolism, which results in substantial morbidity, mortality, and health care expenditures. The Khorana score (range, 0 to 6, with higher scores indicating a higher risk of venous thromboembolism) has been validated to identify patients with cancer at elevated risk for this complication and may help select those who could benefit from thromboprophylaxis. METHODS: We conducted a randomized, placebo-controlled, double-blind clinical trial assessing the efficacy and safety of apixaban (2.5 mg twice daily) for thromboprophylaxis in ambulatory patients with cancer who were at intermediate-to-high risk for venous thromboembolism (Khorana score, ≥2) and were initiating chemotherapy. The primary efficacy outcome was objectively documented venous thromboembolism over a follow-up period of 180 days. The main safety outcome was a major bleeding episode. RESULTS: Of the 574 patients who underwent randomization, 563 were included in the modified intention-to-treat analysis. Venous thromboembolism occurred in 12 of 288 patients (4.2%) in the apixaban group and in 28 of 275 patients (10.2%) in the placebo group (hazard ratio, 0.41; 95% confidence interval [CI], 0.26 to 0.65; P<0.001). In the modified intention-to-treat analysis, major bleeding occurred in 10 patients (3.5%) in the apixaban group and in 5 patients (1.8%) in the placebo group (hazard ratio, 2.00; 95% CI, 1.01 to 3.95; P=0.046). During the treatment period, major bleeding occurred in 6 patients (2.1%) in the apixaban group and in 3 patients (1.1%) in the placebo group (hazard ratio, 1.89; 95% CI, 0.39 to 9.24). CONCLUSIONS: Apixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo.

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DO - 10.1056/NEJMoa1814468

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JO - New England Journal of Medicine

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Apixaban to prevent venous thromboembolism in patients with cancer

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ASJC Scopus Subject Areas

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