In 2004, workers at the Johann Wolfgang Goethe University in Frankfurt am Main led by Professor Ingrid Fleming and coworker, Karin Kohlstedt made a remarkable discovery that they termed “ACE signalling”. Subsequently, searching for previously-unknown relationships between these novel findings and the pathophysiology of coronary artery atherosclerosis, McCormack Pharma’s CEME generated new teachings that distinguished the ACE inhibitor captopril. Potentially, these new teachings could stem the loss of life in an incalculable number of patients who suffer an acute myocardial infarction (MI).

Historically, Fleming’s team showed that binding of an angiotensin I (Ang I)–converting enzyme (ACE) inhibitor to its extracellular target ACE, in addition to inhibiting the conversion of Ang I to Ang II is associated with a sequence of signalling events that results in the increased expression of intracellular ACE (paradoxical ACE).

Within the context of the atherosclerosis plaque macrophage, paradoxical ACE by replenishing inhibited ACE (bound to the inhibitor), could limit the therapeutic efficacy of an ACE inhibitor thus exposing the post-MI patient to the unchecked deleterious effects of ACE, especially in patients with multifocal plaque instability. From those ACE inhibitors included within CEME’s novel teachings, a priori only captopril is demonstrated to act as a dual inhibitor and block both extracellular transmembrane ACE and intracellular paradoxical ACE. This extraordinary finding by CEME potentially positions captopril as the inhibitor of choice in the management of the post-acute MI patient. Worldwide approximately 40 million people are treated with ACE inhibitors. In the United States alone, approximately 14 million people have coronary artery disease, of which 1.5 million will develop acute MI.