A randomized trial of rosuvastatin in the prevention of venous thromboembolism

Robert J Glynn; Eleanor Danielson; Francisco A H Fonseca; Jacques Genest; Antonio M Gotto; John J P Kastelein; Wolfgang Koenig; Peter Libby; Alberto J Lorenzatti; Jean G MacFadyen; Børge Nordestgaard; James Shepherd; James T Willerson; Paul M Ridker

doi:10.1056/NEJMoa0900241

A randomized trial of rosuvastatin in the prevention of venous thromboembolism

Robert J Glynn, Eleanor Danielson, Francisco A H Fonseca, Jacques Genest, Antonio M Gotto, John J P Kastelein, Wolfgang Koenig, Peter Libby, Alberto J Lorenzatti, Jean G MacFadyen, Børge Nordestgaard, James Shepherd, James T Willerson, Paul M Ridker

553 Citations (Scopus)

Abstract

BACKGROUND: Controversy persists regarding the extent of shared pathways between arterial and venous thrombosis and whether treatments of known efficacy for one disease process have consistent benefits for the other. Observational studies have yielded variable estimates of the effect of statin therapy on the risk of venous thromboembolism, and evidence from randomized trials is lacking. METHODS: We randomly assigned 17,802 apparently healthy men and women with both low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to receive rosuvastatin, 20 mg per day, or placebo. We followed participants for the first occurrence of pulmonary embolism or deep-vein thrombosis and performed analyses of the data on an intention-to-treat basis. RESULTS: During a median follow-up period of 1.9 years (maximum, 5.0), symptomatic venous thromboembolism occurred in 94 participants: 34 in the rosuvastatin group and 60 in the placebo group. The rates of venous thromboembolism were 0.18 and 0.32 event per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio with rosuvastatin, 0.57; 95% confidence interval [CI], 0.37 to 0.86; P=0.007); the corresponding rates for unprovoked venous thromboembolism (i.e., occurring in the absence of a known malignant condition, trauma, hospitalization, or surgery) were 0.10 and 0.17 (hazard ratio, 0.61; 95% CI, 0.35 to 1.09; P=0.09) and for provoked venous thromboembolism (i.e., occurring in patients with cancer or during or shortly after trauma, hospitalization, or surgery), 0.08 and 0.16 (hazard ratio, 0.52; 95% CI, 0.28 to 0.96; P=0.03). The rates of pulmonary embolism were 0.09 in the rosuvastatin group and 0.12 in the placebo group (hazard ratio, 0.77; 95% CI, 0.41 to 1.45; P=0.42), whereas the rates of deep-vein thrombosis only were 0.09 and 0.20, respectively (hazard ratio, 0.45; 95% CI, 0.25 to 0.79; P=0.004). Consistent effects were observed in all the subgroups examined. No significant differences were seen between treatment groups in the rates of bleeding episodes. CONCLUSIONS: In this trial of apparently healthy persons, rosuvastatin significantly reduced the occurrence of symptomatic venous thromboembolism. (ClinicalTrials.gov number, NCT00239681.)

Original language	English
Journal	New England Journal of Medicine
Volume	360
Issue number	18
Pages (from-to)	1851-61
Number of pages	11
ISSN	0028-4793
DOIs	https://doi.org/10.1056/NEJMoa0900241
Publication status	Published - 2009

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10.1056/NEJMoa0900241

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Glynn, R. J., Danielson, E., Fonseca, F. A. H., Genest, J., Gotto, A. M., Kastelein, J. J. P., Koenig, W., Libby, P., Lorenzatti, A. J., MacFadyen, J. G., Nordestgaard, B., Shepherd, J., Willerson, J. T., & Ridker, P. M. (2009). A randomized trial of rosuvastatin in the prevention of venous thromboembolism. New England Journal of Medicine, 360(18), 1851-61. https://doi.org/10.1056/NEJMoa0900241

Glynn, RJ, Danielson, E, Fonseca, FAH, Genest, J, Gotto, AM, Kastelein, JJP, Koenig, W, Libby, P, Lorenzatti, AJ, MacFadyen, JG, Nordestgaard, B, Shepherd, J, Willerson, JT & Ridker, PM 2009, 'A randomized trial of rosuvastatin in the prevention of venous thromboembolism', New England Journal of Medicine, vol. 360, no. 18, pp. 1851-61. https://doi.org/10.1056/NEJMoa0900241

@article{e8fd2200841411df928f000ea68e967b,

title = "A randomized trial of rosuvastatin in the prevention of venous thromboembolism",

abstract = "BACKGROUND: Controversy persists regarding the extent of shared pathways between arterial and venous thrombosis and whether treatments of known efficacy for one disease process have consistent benefits for the other. Observational studies have yielded variable estimates of the effect of statin therapy on the risk of venous thromboembolism, and evidence from randomized trials is lacking. METHODS: We randomly assigned 17,802 apparently healthy men and women with both low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to receive rosuvastatin, 20 mg per day, or placebo. We followed participants for the first occurrence of pulmonary embolism or deep-vein thrombosis and performed analyses of the data on an intention-to-treat basis. RESULTS: During a median follow-up period of 1.9 years (maximum, 5.0), symptomatic venous thromboembolism occurred in 94 participants: 34 in the rosuvastatin group and 60 in the placebo group. The rates of venous thromboembolism were 0.18 and 0.32 event per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio with rosuvastatin, 0.57; 95% confidence interval [CI], 0.37 to 0.86; P=0.007); the corresponding rates for unprovoked venous thromboembolism (i.e., occurring in the absence of a known malignant condition, trauma, hospitalization, or surgery) were 0.10 and 0.17 (hazard ratio, 0.61; 95% CI, 0.35 to 1.09; P=0.09) and for provoked venous thromboembolism (i.e., occurring in patients with cancer or during or shortly after trauma, hospitalization, or surgery), 0.08 and 0.16 (hazard ratio, 0.52; 95% CI, 0.28 to 0.96; P=0.03). The rates of pulmonary embolism were 0.09 in the rosuvastatin group and 0.12 in the placebo group (hazard ratio, 0.77; 95% CI, 0.41 to 1.45; P=0.42), whereas the rates of deep-vein thrombosis only were 0.09 and 0.20, respectively (hazard ratio, 0.45; 95% CI, 0.25 to 0.79; P=0.004). Consistent effects were observed in all the subgroups examined. No significant differences were seen between treatment groups in the rates of bleeding episodes. CONCLUSIONS: In this trial of apparently healthy persons, rosuvastatin significantly reduced the occurrence of symptomatic venous thromboembolism. (ClinicalTrials.gov number, NCT00239681.)",

author = "Glynn, {Robert J} and Eleanor Danielson and Fonseca, {Francisco A H} and Jacques Genest and Gotto, {Antonio M} and Kastelein, {John J P} and Wolfgang Koenig and Peter Libby and Lorenzatti, {Alberto J} and MacFadyen, {Jean G} and B{\o}rge Nordestgaard and James Shepherd and Willerson, {James T} and Ridker, {Paul M}",

note = "Keywords: Aged; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, LDL; Double-Blind Method; Female; Fluorobenzenes; Hemorrhage; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Male; Middle Aged; Pulmonary Embolism; Pyrimidines; Risk; Sulfonamides; Venous Thromboembolism; Venous Thrombosis",

year = "2009",

doi = "10.1056/NEJMoa0900241",

language = "English",

volume = "360",

pages = "1851--61",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "18",

}

TY - JOUR

T1 - A randomized trial of rosuvastatin in the prevention of venous thromboembolism

AU - Glynn, Robert J

AU - Danielson, Eleanor

AU - Fonseca, Francisco A H

AU - Genest, Jacques

AU - Gotto, Antonio M

AU - Kastelein, John J P

AU - Koenig, Wolfgang

AU - Libby, Peter

AU - Lorenzatti, Alberto J

AU - MacFadyen, Jean G

AU - Nordestgaard, Børge

AU - Shepherd, James

AU - Willerson, James T

AU - Ridker, Paul M

N1 - Keywords: Aged; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, LDL; Double-Blind Method; Female; Fluorobenzenes; Hemorrhage; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Male; Middle Aged; Pulmonary Embolism; Pyrimidines; Risk; Sulfonamides; Venous Thromboembolism; Venous Thrombosis

PY - 2009

Y1 - 2009

N2 - BACKGROUND: Controversy persists regarding the extent of shared pathways between arterial and venous thrombosis and whether treatments of known efficacy for one disease process have consistent benefits for the other. Observational studies have yielded variable estimates of the effect of statin therapy on the risk of venous thromboembolism, and evidence from randomized trials is lacking. METHODS: We randomly assigned 17,802 apparently healthy men and women with both low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to receive rosuvastatin, 20 mg per day, or placebo. We followed participants for the first occurrence of pulmonary embolism or deep-vein thrombosis and performed analyses of the data on an intention-to-treat basis. RESULTS: During a median follow-up period of 1.9 years (maximum, 5.0), symptomatic venous thromboembolism occurred in 94 participants: 34 in the rosuvastatin group and 60 in the placebo group. The rates of venous thromboembolism were 0.18 and 0.32 event per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio with rosuvastatin, 0.57; 95% confidence interval [CI], 0.37 to 0.86; P=0.007); the corresponding rates for unprovoked venous thromboembolism (i.e., occurring in the absence of a known malignant condition, trauma, hospitalization, or surgery) were 0.10 and 0.17 (hazard ratio, 0.61; 95% CI, 0.35 to 1.09; P=0.09) and for provoked venous thromboembolism (i.e., occurring in patients with cancer or during or shortly after trauma, hospitalization, or surgery), 0.08 and 0.16 (hazard ratio, 0.52; 95% CI, 0.28 to 0.96; P=0.03). The rates of pulmonary embolism were 0.09 in the rosuvastatin group and 0.12 in the placebo group (hazard ratio, 0.77; 95% CI, 0.41 to 1.45; P=0.42), whereas the rates of deep-vein thrombosis only were 0.09 and 0.20, respectively (hazard ratio, 0.45; 95% CI, 0.25 to 0.79; P=0.004). Consistent effects were observed in all the subgroups examined. No significant differences were seen between treatment groups in the rates of bleeding episodes. CONCLUSIONS: In this trial of apparently healthy persons, rosuvastatin significantly reduced the occurrence of symptomatic venous thromboembolism. (ClinicalTrials.gov number, NCT00239681.)

AB - BACKGROUND: Controversy persists regarding the extent of shared pathways between arterial and venous thrombosis and whether treatments of known efficacy for one disease process have consistent benefits for the other. Observational studies have yielded variable estimates of the effect of statin therapy on the risk of venous thromboembolism, and evidence from randomized trials is lacking. METHODS: We randomly assigned 17,802 apparently healthy men and women with both low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to receive rosuvastatin, 20 mg per day, or placebo. We followed participants for the first occurrence of pulmonary embolism or deep-vein thrombosis and performed analyses of the data on an intention-to-treat basis. RESULTS: During a median follow-up period of 1.9 years (maximum, 5.0), symptomatic venous thromboembolism occurred in 94 participants: 34 in the rosuvastatin group and 60 in the placebo group. The rates of venous thromboembolism were 0.18 and 0.32 event per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio with rosuvastatin, 0.57; 95% confidence interval [CI], 0.37 to 0.86; P=0.007); the corresponding rates for unprovoked venous thromboembolism (i.e., occurring in the absence of a known malignant condition, trauma, hospitalization, or surgery) were 0.10 and 0.17 (hazard ratio, 0.61; 95% CI, 0.35 to 1.09; P=0.09) and for provoked venous thromboembolism (i.e., occurring in patients with cancer or during or shortly after trauma, hospitalization, or surgery), 0.08 and 0.16 (hazard ratio, 0.52; 95% CI, 0.28 to 0.96; P=0.03). The rates of pulmonary embolism were 0.09 in the rosuvastatin group and 0.12 in the placebo group (hazard ratio, 0.77; 95% CI, 0.41 to 1.45; P=0.42), whereas the rates of deep-vein thrombosis only were 0.09 and 0.20, respectively (hazard ratio, 0.45; 95% CI, 0.25 to 0.79; P=0.004). Consistent effects were observed in all the subgroups examined. No significant differences were seen between treatment groups in the rates of bleeding episodes. CONCLUSIONS: In this trial of apparently healthy persons, rosuvastatin significantly reduced the occurrence of symptomatic venous thromboembolism. (ClinicalTrials.gov number, NCT00239681.)

U2 - 10.1056/NEJMoa0900241

DO - 10.1056/NEJMoa0900241

M3 - Journal article

C2 - 19329822

SN - 0028-4793

VL - 360

SP - 1851

EP - 1861

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 18

ER -

A randomized trial of rosuvastatin in the prevention of venous thromboembolism

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