Role of Coronary Vasoconstriction in Ischemic Heart Disease and Search for Novel Therapeutic Targets

Atherothrombosis has long been recognized as an important mechanism of cardiac events in ischemic heart disease, and large multicenter clinical studies have shown the benefit of antiplatelet agents, statins, beta-blockers and angiotensin converting enzyme inhibitors in preventing these events. However, more recent studies have been less successful at showing incremental gains in targeting these mechanisms, suggesting that the limits of this strategy have been exploited. Coronary vasoconstriction is another important mechanism in ischemic heart disease but has received little attention and yet is a potential therapeutic target. In the current review, the reasons why coronary vasconstriction has received insufficient consideration are explored. In particular, we need to change our approach from lumping heterogeneous clinical entities together to focusing on clinically-discrete homogeneous groups with a common mechanism and thus therapeutic target. The role of coronary vasoconstriction is examined in the various ischemic syndromes (variant angina, chronic stable angina, acute coronary syndromes and syndrome X) and the underlying mechanisms discussed. Finally, in order to advance studies in this field, an innovative research strategy is proposed, including: (1) selection of paradigmatic cases for the various ischemic syndromes; (2) candidate therapeutic targets; and (3) approaches in assessing the clinical efficacy of these potential therapies. (Circ J 2009; 73: 394-403)