Inhibition of the Sodium-Hydrogen Exchanger With Cariporide to Prevent Myocardial Infarction in High-Risk Ischemic Situations: Main Results of the GUARD During Ischemia Against Necrosis (GUARDIAN) Trial - GUARDIAN

Description:

Inhibition of the Sodium-Hydrogen Exchanger With Cariporide to Prevent Myocardial Infarction in High-Risk Ischemic Situations: Main Results of the GUARD During Ischemia Against Necrosis (GUARDIAN) Trial

Hypothesis:

Does cariporide, a potent and specific inhibitor of the transmembrane sodium/hydrogen exchanger prevent myocardial cell necrosis?

Study Design

Study Design:

Patients Enrolled: 11590

Drug/Procedures Used:

Patients with unstable angina or non-ST-elevation myocardial infarction (MI) or undergoing high-risk percutaneous or surgical revascularization (n = 11,590) were randomized to receive placebo or 1 of 3 doses of cariporide (20mg, 80mg, or 120mg as a 60 minute infusion every 8 hours) for 2 to 7 days.

Principal Findings:

Cariporide failed to show any benefit with the two lower doses over placebo on the primary end point of death or MI assessed after 36 days with a non-significant 10% risk reduction with a dose of 120 mg every 8 hours (98% CI 5.5% to 23.4%, p = 0.12). This benefit with the highest dose was limited to patients undergoing bypass surgery (risk reduction 25%, 95% CI 3.1% to 41.5%, p = 0.03) and was maintained after 6 months. No effect was seen on mortality with any dose. While the highest dose reduced the rate of Q-wave MI by 32% across all groups dose (2.6% vs. 1.8%, p = 0.03), the rate of non ST elevation MI was reduced only in patients undergoing surgery (7.1% vs. 3.8%, p = 0.005). Clinically serious adverse events were similar for placebo and all 3 doses of cariporide.

Cariporide demonstrated no significant beneficial effect across a wide range of clinical spectrum of coronary artery disease.

Interpretation:

The promising results of earlier experimental and pilot studies as to the beneficial cardioprotective effects of cariporide were not echoed in this large phase three trial. Although the risk of death or MI and the risk of non-fatal MI were reduced in the group undergoing coronary artery bypass surgery (albeit predefined), this should be interpreted with caution because it applies to only 1 of 9 study subgroups and may be due to chance. This beneficial effect in surgical patients needs confirmation in a future prospective trial.

References:

Théroux P, Chaitman BR, Danchin N. Circulation 2000;102:3032-8.

Clinical Topics: Cardiac Surgery, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Interventions and Coronary Artery Disease

Keywords: Coronary Artery Disease, Myocardial Infarction, Risk Reduction Behavior, Sodium-Hydrogen Antiporter, Coronary Artery Bypass, Sulfones


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