A Randomized Trial of Rosuvastatin in the Prevention of Venous Thromboembolism

Abstract

BACKGROUNDControversy 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.METHODSWe 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.RESULTSDuring 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.CONCLUSIONSIn this trial of apparently healthy persons, rosuvastatin significantly reduced the occurrence of symptomatic venous thromboembolism. (ClinicalTrials.gov number, NCT00239681.)AstraZenecaNational Institute on AgingHarvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USAHarvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02215 USAUniversidade Federal de São Paulo, São Paulo, BrazilMcGill Univ, Ctr Hlth, Montreal, PQ, CanadaCornell Univ, Weill Med Coll, New York, NY 10021 USAUniv Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, NetherlandsUniv Ulm, Ulm, GermanyHosp Cordoba, Cordoba, ArgentinaUniv Copenhagen, Herlev Hosp, Copenhagen Univ Hosp, DK-2730 Herlev, DenmarkUniv Glasgow, Glasgow, Lanark, ScotlandSt Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX USAUniversidade Federal de São Paulo, São Paulo, BrazilNational Institute on Aging: AG031061Web of Scienc