By Em Brown
ORLANDO, Fla -- March 31, 2009 -- Rosuvastatin cuts the risk of venous thromboembolism (VTE) by over 40% in apparently healthy adults with low low-density lipoprotein (LDL) cholesterol and elevated high-sensitivity C-reactive protein (CRP), according to research presented here at the American College of Cardiology (ACC) 58th Annual Scientific Session.
Findings from Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) were presented here on March 29 at a late-breaking clinical trials session. JUPITER involved 17,802 initially healthy men and women randomised to rosuvastatin 20 mg daily or placebo. Median follow-up was 1.9 years (maximum 5 years).
Rosuvastatin 20 mg daily was shown to cut the risk of VTE by 43% (P = .007) and was also associated with a significant 55% (P = .004) reduction in the risk of deep vein thrombosis (DVT) and a nonsignificant 23% reduction in pulmonary embolism (P = .42).
There were 94 cases of symptomatic VTE overall in JUPITER, with 34 cases in the rosuvastatin group and 60 in the placebo group.
The rates of VTE were 0.18 and 0.32 events/100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio [HR] with rosuvastatin, 0.57; 95% confidence interval [CI], 0.37-0.86; P = .007).
Rates for unprovoked VTE (occurring without a known cause, such as malignancy, trauma, hospitalisation, or surgery) were 0.10 and 0.17 (HR, 0.61; 95% CI, 0.35-1.09; P = .09) for the active and placebo groups, respectively.
Rates for provoked VTE (occurring with a known cause) were 0.08 and 0.16 events/100 person-years (HR, 0.52; 95% CI, 0.28-0.96; P = .03) for rosuvastatin and placebo, respectively.
Rates for pulmonary embolism were 0.09 in the rosuvastatin group and 0.12 in the placebo group (HR, 0.77; 95% CI, 0.41-1.45; P = .42).
Rates of DVT were 0.09 and 0.20 (HR, 0.45; CI, 0.25-0.79; P = .004), with active treatment and placebo, respectively.
Rates were similar for all subgroups. There were no significant differences between rosuvastatin and placebo in bleeding rates.
"This risk reduction appears to be an independent benefit of statin use, and beyond the reduction in the risk of arterial thrombosis," announced Paul M. Ridker, MD, Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
"Statins probably don't prevent VTE through lipid reduction," Dr. Ridker told meeting attendees. "About half the JUPITER population had elevated CRP levels. ... Statins probably cause a shift in cell signalling that results in mild anticoagulation."
"Once again, we saw virtually no relation between LDL level and CRP level on an individual patient basis," Dr. Ridker said. "We need to know both values ... and it is best if the LDL level is below 70 mg/dL and CRP has been lowered more than 50%."
"Compared to placebo, it's always better to be on the drug," Dr. Ridker asserted. "The bottom line is that elevated LDL or CRP is associated with risk of VTE."
Dr. Ridker proposes widening the goal of statin treatment to include prevention of both venous and arterial thromboembolism and death.
Funding for JUPITER was supported by AstraZeneca Pharmaceuticals LP, which previously announced that it expects to file a regulatory submission including the JUPITER data within the next few months.
These findings were published simultaneously in The New England Journal of Medicine (Glynn RJ et al. [Published online ahead of print March 29, 2009]. doi:10.1056/NEJMoa0900241).
[Presentation title: A Randomized Trial of Rosuvastatin in the Prevention of Venous Thromboembolism: The JUPITER Trial. Abstract 404]
E-Mail this DGDispatch to a colleague
