Pharmacology and clinical assessment of cariporide for the treatment coronary artery diseases

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Abstract
Myocardial protection through pharmacological approaches represents a large therapeutic challenge and is an important therapeutic strategy in patients with coronary artery disease, particularly after myocardial infarction. Extensive animal experiments have repeatedly demonstrated the efficacy of sodium-hydrogen exchange (NHE) inhibition as a potent cardioprotective approach. The heart possesses primarily the NHE1 isoform which has led to the development of NHE1 specific inhibitors for cardiovascular therapeutics. Cariporide (HOE 642) is the first of such agents to have been developed and subjected to clinical trial. Preclinical studies with cariporide revealed excellent protection against necrosis, apoptosis, arrhythmias and mechanical dysfunction in hearts subjected to ischaemia and reperfusion. Cariporide has recently been evaluated in a large dose-finding Phase II/Phase III clinical trial (GUARDIAN) to assess its efficacy in patients with acute coronary syndromes. Overall results failed to demonstrate ...

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