Krista Fajman

EBM 8/14/09

“A Randomized Trial of Rosuvastatin in the Prevention of Venous Thromboembolism”

NEJM. April 30, 2009. Vol 360. No 18. pp 1851-1861

Background: The JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) examined whether patients with LDL < 130 and CRP > 2 received cardiovascular benefit from statins. A specified secondary end point of the JUPITER trial was the occurrence of venous thromboembolism (DVT or PE). Controversy exists over the shared pathways between arterial and venous disease and whether statins would also be beneficial for venous thromboembolic disease.

Study Type: randomized, double-blind, placebo-controlled, multicenter trial (1315 site in 26 countries)

Study participants:

  • 17,802 apparently healthy men 50 years and older, and women 60 years and older, with LDL < 130, high sensitivity CRP > 2, triglycerides < 500
  • Exclusion criteria included previous or current use of lipid lowering therapy, current use of postmenopausal hormone replacement therapy, hepatic dysfunction, CK > 3X upper limit of normal, creatinine > 2, diabetes, uncontrolled hypertension, cancer within 5 years before enrollment, uncontrolled hypothyroidism, recent history of EtOH or drug abuse
  • No inflammatory conditions including arthritis, lupus, IBD

Intervention: Randomized to receive Rosuvastatin 20 mg PO daily or placebo daily.

End Points:

  • Patients were followed for the first occurrence of symptomatic DVT or PE. Needed diagnostic testing as proof.
  • Evaluated whether the DVTs/PEs were provoked or unprovoked. Thrombus was provoked if it occurred in the setting of recent trauma, hospitalization, surgery or malignancy within 3 months prior to or after the diagnosis of thrombus.

Weaknesses:

  • 4 week placebo run in phase
  • Study was limited to healthy patients.
  • Limited follow up time for a drug that we would be asking patients to take indefinitely. Median follow up time was 1.9 years since the JUPITER trial was stopped early.
  • Trial was financed and initiated by Astra Zeneca.

Strengths:

  • Number of participants – 17,802, diverse patient population although relatively healthy
  • Randomized, double blind, placebo controlled, multicenter

Validity:

  • Was the assignment of patients to treatment randomized? Yes
  • Was randomization concealed? Yes
  • Was follow up complete? Trial was stopped early
  • Were patients analyzed in the groups to which they were randomized? Yes, intention to treat analysis
  • Were patients, health workers, and study personnel blind to treatment? Yes
  • Were the groups similar at the start of the trial? Yes
  • Aside from the experimental intervention, were the groups treated equally? Yes

Reported Results:

  • Combination of primary cardiac endpoint or VTE: 173 had primary cardiac event or VTE on Rosuvastatin and 305 had cardiac event or VTE on placebo (p < 0.001)
  • Symptomatic DVT or PE occurred in 94 patients: 34 patients in the Rosuvastatin group and 60 patients in the placebo group (p = 0.007).
  • Of 34 events in the Rosuvastatin group, 17 were PE and 17 were DVT. In the placebo group, there were 22 PEs and 38 DVTs.
  • Of 94 patients with symptomatic disease, 44 were considered provoked (malignancy, trauma, hospitalization, surgery, p = 0.09) and 50 were considered unprovoked, p = 0.03.
  • How does this influence how we treat our patients?
  • Based on these results, would you start someone on a statin to prevent thromboembolic disease?