Objectives Statins improve overall outcomes after noncardiac surgery. on postoperative day

Objectives Statins improve overall outcomes after noncardiac surgery. on postoperative day 3. Due to difficulty enrolling statin-naive patients the study was stopped at the interim analysis. Results Postoperative complications occurred in 16 of 72 (22%) patients receiving placebo and in 8 of 65 (12%) receiving atorvastatin P=0.13). For patients undergoing major anatomic resection there were a total of 24 complications in 15 of 45 patients who received placebo and 8 complications in 7 of 43 atorvastatin-treated patients (P=0.04). Plasma levels of CVT 6883 C-reactive protein (CRP) tumor necrosis factor-α (TNFα) and CVT 6883 myeloperoxidase (MPO) did not differ between the two treatment arms during the study. Conclusions After a 2-week perioperative course of atorvastatin (40 mg) in statin-na?ve patients undergoing major pulmonary resection we found evidence of a reduction in the number of clinically important cardiovascular and pulmonary complications compared with placebo. These promising results merit evaluation in a larger perhaps multicenter study. Introduction Inflammatory and oxidative changes have been implicated as etiologic CVT 6883 mechanisms for a variety of postoperative complications following thoracic surgery such as atrial fibrillation/flutter (AF) acute coronary syndromes stroke and respiratory failure.1-3 Postoperative AF (POAF) is a common complication occurring in roughly 16% of all patients with increasing frequency in elderly patients.4 5 The rate of postoperative pulmonary complications (pneumonia and respiratory failure) is approximately 10% with severe lung injury resulting in mortality rates of up to 30%.6 Because these CVT 6883 complications result in prolonged hospital stay resource utilization and long-term sequelae prevention is essential. Preoperative use of statins in patients with cardiovascular disease has been shown to reduce perioperative cardiovascular morbidity but its impact in patients undergoing pulmonary resection is unknown.3 7 The presumed mechanism of the benefit of statins is through Rabbit Polyclonal to PODXL2. inhibition of inflammation.3 7 8 Some sequelae of lung injury after thoracic surgery include increased inflammation (C-reactive protein (CRP)) leukocyte activation (myeloperoxidase (MPO)) and other acute-phase inflammatory markers such as tumor necrosis factor-α (TNFα).1 2 9 MPO and CRP levels which are also increased in patients with acute cardiovascular disease may be reduced by statins.10-12 Based on promising experimental13-15 and observational studies from our institution9 and others’ 16 we hypothesized that compared with placebo the use of moderate-potency atorvastatin would be associated with a decreased composite rate of clinically significant cardiovascular and pulmonary complications after lung resection. A secondary aim was to compare perioperative changes in levels of CRP TNFα and MPO between the two treatment arms. Materials and Methods Patient Population This was a single-center prospective double-blind randomized controlled trial of perioperative moderate dose atorvastatin versus placebo for patients undergoing elective pulmonary resection. Inclusion criteria included patients: 1) undergoing elective pulmonary resection; 2) age greater than 18 years; 3) no active statin use. Patients were excluded if they: 1) had a history of chronic atrial fibrillation; 2) were taking class I or III antiarrhythmic drugs or corticosteroids; 3) were not in sinus rhythm at the time of the screening; or 4) had abnormal liver function tests or CVT 6883 renal insufficiency. A negative pregnancy test was required for women of child-bearing age. Beta-blocker and calcium channel blocker use were continued postoperatively to avoid withdrawal. The study was approved by the institutional review board at Memorial Sloan Kettering Cancer Center and all patients provided written informed consent. Atorvastatin Prophylaxis Once enrolled patients were randomized between atorvastatin and placebo in permuted blocks between the Department of Epidemiology and Biostatistics and the Department of Pharmacy in accordance with good medical practice requirements. Blinding of atorvastatin and placebo pills was performed by Department of Pharmacy Division of Research..