Orthopedic patients are at risk for adverse postoperative cardiovascular outcomes.
This pilot randomized controlled trial (RCT) of atorvastatin vs. placebo in orthopedic surgery patients was performed in order to assess: (1) the prevalence of perioperative myocardial injury; (2) the effect of atorvastatin on perioperative inflammation; and (3) the feasibility of performing a large RCT of statin therapy in orthopedic patients.
Hip fracture (hip Fx) and total hip and knee replacement (THR and TKR) patients were randomized 1:1 to atorvastatin 40 mg daily vs. placebo, starting preoperatively and continuing until postoperative day (POD) 45. High-sensitivity cardiac troponin I (hs-cTnI), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were measured preoperatively and on POD 2. Patients were monitored for adverse events until POD 90.
Five hundred fifty-six patients were screened, 22 were recruited (4 hip Fx, 11 THR, 7 TKR), and 2 withdrew. Most (80%) had detectable hs-cTnI (> 1.1 pg/mL) preoperatively. Twenty percent had a perioperative rise in hs-cTnI (≥ 10 pg/mL), which was not blunted by atorvastatin. Hs-CRP rose in 19/20 patients, and IL-6 rose in all patients. However, atorvastatin did not blunt the rise in these inflammatory biomarkers. On POD 2, IL-6 and hs-cTnI levels correlated (ρ = 0.59, p = 0.02). Recruitment was limited by the high prevalence of statin use in the screened population and a high prevalence of exclusions among hip fracture patients.
Perioperative myocardial injury and inflammation are common in orthopedic patients and do not appear to be reduced in those randomized to atorvastatin.
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This trial was funded by the Weill Cornell Clinical and Translational Science Center (UL1TR000457-06). Pfizer provided study drug and matching placebo for a subset of patients (the remainder was compounded locally), but had no involvement in the design of the trial, analysis of the results, or manuscript preparation. Abbott provided reagents for hs-cTnI testing.
Conflict of Interest
Jaclyn D. Szymonifka, MA; Matthew T. Rondina, MD, MS; Margaret Bogardus, BA; Scott C. Woller, MD; Scott M. Stevens, MD; Kerri Merritt; Gerard Moskowitz, PhD; Alejandro Gonzalez Della Valle, MD; and Eva Flores, MD, have declared that they have no conflict of interest. Mitchell G. Scott, PhD, reports a grant from Abbott Diagnostics during the conduct of the study. He also reports grants from Instrumentation Laboratory and Siemens Healthcare; other from Becton, Dickinson and Roche Diagnostics, outside the work. Anne R. Bass, MD, reports grants from Weill Cornell Clinical and Translational Science Center (UL1TR000457-06) and other from Pfizer and Abbott Labs during the conduct of the study. Charles Eby, MD, reports grants from Siemens Healthcare Diagnostics and personal fess from Boehringer Ingelheim and Bayer Pharmaceuticals, outside the work. Brian F. Gage, MD, MSc, reports ownership of stock in at least 1 pharmaceutical company that markets or manufactures statins.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5).
Informed consent was obtained from all patients for being included in the study.
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Level of evidence: double-blind, randomized controlled trial, level II
The work was performed at Hospital for Special Surgery, New York Presbyterian Hospital, University of Utah (cytokine assays) and Washington University in St. Louis (hs-troponin and hs-CRP assays).
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Bass, A.R., Szymonifka, J.D., Rondina, M.T. et al. Postoperative Myocardial Injury and Inflammation Is Not Blunted by a Trial of Atorvastatin in Orthopedic Surgery Patients. HSS Jrnl 14, 67–76 (2018). https://doi.org/10.1007/s11420-017-9577-1
- C-reactive protein
- myocardial ischemia