Lowering the Risk of Operative Complications Using Atorvastatin Loading Dose (LOAD)

• Composite outcome [ Time Frame: 30 days ]
  Composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery and stroke at 30 days.
  
  

• All-cause mortality [ Time Frame: 30 days ]
  Death from any cause.
  
  
• Myocardial injury after noncardiac surgery (MINS) [ Time Frame: 30 days ]
  An elevated cardiac troponin measurement judged due to cardiac ischemia (i.e., there was no evidence of a non-ischemic etiology like sepsis or pulmonary embolism).
  
  
• Stroke [ Time Frame: 30 days ]
  New neurologic symptom with compatible lesion on brain imaging and confirmation by a neurologist of the diagnosis of stroke.
  
  
• Myocardial infarction [ Time Frame: 30 days ]
  Rate of myocardial infarction as defined by any 2 of: typical chest pain OR typical ECG changes (ST-segment depression, ST-segment elevation, new Q waves, transitory T wave inversion) OR new rise in troponin levels (CK-MB levels if unavailable) OR new wall motion abnormality on echocardiogram. Pathological confirmation of myocardial necrosis on necropsy will also be accepted
  
  
• Cardiovascular death [ Time Frame: 30 days ]
  Evidence of death primarily caused by one of the following: acute myocardial infarction, stroke, pulmonary embolism, heart failure or ventricular arrhythmias.
  
  
• Pulmonary embolism [ Time Frame: 30 days ]
  Clinical signs accompanied by high-probability ventilation-perfusion lung scan or a filling defect of the pulmonary artery or its branches in a conventional arteriography or multi-slice spiral tomography.
  
  
• Deep venous thrombosis [ Time Frame: 30 days ]
  Any signs or symptoms of deep vein thrombosis confirmed by adequate images on ultrasound, computed tomography or angiography
  
  
• Clinically relevant atrial fibrillation [ Time Frame: 30 days ]
  A newly diagnosed atrial fibrillation that results in angina, heart failure, hypotension, or that requires treatment with an anti-arrhythmic drug or electric cardioversion
  
  
• Rhabdomyolysis [ Time Frame: 30 days ]
  elevation of CPK levels higher than 5 times the normal upper limit and myalgia or any CPK elevation higher than 10 times the upper limit, regardless of symptoms.
  
  

Cardiovascular complications, such as myocardial infarction (MI) and stroke are common in the perioperative period of noncardiac surgeries. To the moment there are no safe and effective interventions to reduce vascular events in this scenario. Data from observational studies and small-sized randomized controlled trials (RCTs) have shown promising results in terms of risk reduction. In addition, experimental data have indicated that statins have acute anti-inflammatory properties, which promote the stabilization of atherosclerotic lesions and, therefore, might reduce the risk of MI, even in the short term. This study was designed to explore the effects of atorvastatin, as compared with placebo, on the 30-day risk of a composite of death, nonfatal Myocardial Injury after Noncardiac Surgery (MINS), or stroke among patients who undergo noncardiac surgery.

The study was conducted in accordance with the prespecified protocol and reached successful enrollment rates when, by the end of 2014 the steering committee was invited to join an international initiative and participate in a much larger clinical trial to investigate this relevant question. Due to this outstanding possibility, the steering committee decided to redesign the study which is now formatted as an exploratory trial. As described, the study was completed with the inclusion of 648 participants in June, 2015.