GUARD During Ischemia Against Necrosis (GUARDIAN) trial in acute coronary syndromes.

The plasma membrane sodium-hydrogen exchange system plays a major role in the pathophysiology of myocardial ischemia and reperfusion injury. The GUARD During Ischemia Against Necrosis (GUARDIAN) trial was undertaken to assess the potential clinical benefits of cariporide, a novel inhibitor of the sodium-hydrogen exchanger, in patients with acute coronary syndromes at risk of myocardial necrosis. This prospective, doubleblind, randomized, multicenter trial enrolled 11,733 patients who had unstable angina/non-Q-wave myocardial infarction (MI), or who required high-risk percutaneous interventions or coronary bypass surgery. Strict entry criteria were applied to ensure the enrollment of a population at high risk of developing complications. The patients were randomized to receive intravenous cariporide 20, 80, or 120 mg every 8 hours or placebo every 8 hours. Treatment was applied for the period of risk between 48 hours and 7 days. The primary efficacy endpoint was a composite of all-cause mortality and MI at 36 days. Secondary endpoints included the occurrence of the composite endpoint at day 10, events related to left ventricular dysfunction at day 36 and 6 months, extent of infarction, and refractory ischemia at day 36. Enrollment was completed in August 1998, and the results were presented at the American College of Cardiology meeting in New Orleans, Louisiana, USA, in March 1999.