title: A review of the GUARDIAN trial results: clinical implications and the significance of elevated perioperative CK-MB on 6-month survival.
abstract: BACKGROUND
  The Guard During Ischemia Against Necrosis (GUARDIAN) trial was designed to determine whether cariporide, a selective sodium-hydrogen exchanger inhibitor, reduces the combined incidence of all-cause mortality and myocardial infarction (MI) in patients at risk of myocardial necrosis and to assess the safety and tolerability of this drug.
  
  
  RESULTS
  The study population consisted of 11,590 patients who were hospitalized for an acute coronary syndrome or were undergoing high-risk percutaneous coronary intervention or coronary artery bypass grafting (CABG). Patients were enrolled and randomized to one of three doses of cariporide (20, 80, or 120 mg), or placebo, administered as a 60-minute infusion every 8 hours for two to seven days. At day 36, patients treated with cariporide 120 mg demonstrated a 10% risk reduction in death or MI compared with placebo (p = 0.12). At this dose, patients undergoing CABG experienced a 25% risk reduction in death or MI (p = 0.03), which was sustained through six months (p = 0.033). The improvement resulted primarily from a 32% risk reduction in nonfatal MI (p = 0.007). Cariporide was well tolerated; most adverse events were mild and transient. Data from the GUARDIAN trial indicate that myocardial muscle creatine kinase isoenzyme (CK-MB) values of >10 times the upper limit of normal during the initial 48 hours after CABG are associated with significantly increased six-month mortality (p < 0.001); the six-month mortality risk is similar to that observed in acute coronary syndrome patients, even after adjustment for baseline variables known to impact long-term prognosis.
  
  
  CONCLUSIONS
  Although the results of the GUARDIAN trial failed to demonstrate overall clinical benefit, cariporide 120 mg reduced the rate of death and MI in patients undergoing CABG. Cariporide may provide a cardioprotective benefit in CABG patients at high-risk of myocardial necrosis.
authors.affiliation: St. Louis University School of Medicine, St. Louis, Missouri 63117, USA. chaitman@slu.edu
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Chaitman
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D003402:Creatine Kinase / Q000097:blood*; D052279:Creatine Kinase, MB Form; D006146:Guanidines / Q000627:therapeutic use*; D006801:Humans; D007527:Isoenzymes / Q000097:blood*; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D016032:Randomized Controlled Trials as Topic; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors; D013450:Sulfones / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D007527:Isoenzymes; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form