Pilot Study of Atorvastatin for Orthopedic Surgery Patients
Condition: Hip Fracture; Myocardial Ischemia; Inflammation
MeSH terms: Myocardial Ischemia; Coronary Artery Disease; Inflammation; Ischemia; Hip Fractures
Study type: Interventional
Phase: Phase 2

Summary: 
      Up to 35% of hip fracture patients have been shown to experience heart injury after surgery,
      and as many as 10% have a heart attack or die in the three months after surgery. Hip and knee
      arthroplasty patients are also at risk of cardiovascular complications. Patients who have
      these complications have higher levels of inflammation postoperatively. Statins (such as
      atorvastatin/Lipitor) lower cholesterol and also lessen inflammation. Both of these effects
      are important in preventing heart attacks. Statins have been shown to reduce the risk of
      heart attacks in non-surgical patients, and to protect from heart attacks in patients having
      heart surgery. Whether statins can prevent heart attacks in orthopedic patients is not known.

      In this pilot study the investigators will treat 30 orthopedic surgery patients (hip
      fracture, hip or knee arthroplasty) with either atorvastatin or placebo (a capsule with no
      study drug). Patients will start the study drug prior to surgery and take it for 45 days
      after surgery. Neither the doctors nor the patients will know whether they are taking
      atorvastatin or placebo. The investigators will look for evidence of inflammation and heart
      injury after surgery. The investigators hypothesize that atorvastatin will lessen the degree
      of postoperative inflammation found in these patients. In this study, the investigators will
      use a very sensitive test of heart injury that can detect problems even when patients have no
      symptoms. The investigators hypothesize that this test will demonstrate silent heart injury
      in over 50% of the hip fracture patients and over 30% of arthroplasty patients in our study.

      The results of this trial will help us to develop a larger study in 1000 hip fracture and
      joint replacement patients to determine whether atorvastatin protects orthopedic surgery
      patients from heart injury and other complications of surgery.
    

Detailed description: 
      -  Thirty statin-naïve patients ≥ 65 years of age admitted to New York Presbyterian
           Hospital or Hospital for Special Surgery with an acute hip fracture, or for elective hip
           or knee arthroplasty will be randomized in a 1:1 ratio to atorvastatin 40 mg daily or
           matching placebo.

        -  Atorvastatin will be initiated at least 4 hours prior to hip fracture surgery, or 4 days
           prior to arthroplasty, and will be continued until postoperative day (POD) 45.

        -  Patients will be assessed daily in the hospital for adverse events.

        -  Patients will be contacted by telephone weekly for four weeks after surgery and again on
           POD 45 and POD 90.

        -  Patients will mail back study medication bottles on POD 45 for pill counts to assess
           compliance.

        -  High sensitivity cardiac troponin I (hs-cTnI) will be measured pre-operatively (prior to
           atorvastatin therapy) and on POD 2.

        -  High sensitivity C-reactive protein (hs-CRP), and a panel of cytokines (IL-1β, IL-2,
           IL-2r, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, tumor necrosis factor
           (TNF)-α, interferon (IFN)-γ, and soluble (s)CD-40L) will be measured preoperatively and
           on POD 2.
    

Intervention name(s): Atorvastatin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Atorvastatin or placebo will be started at least 4 hours prior to surgery, and continued nightly until postoperative day 45
Other intervention name(s): Lipitor
Intervention MeSH terms: Atorvastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: hip fracture; myocardial ischemia; statin; surgery; troponin; complication; arthroplasty; hip; knee; orthopedic; atorvastatin; cardiovascular