Metabolic manipulation in ischaemic heart disease, a novel approach to treatment

Antianginal drugs that exert their anti-ischaemic effects primarily by altering myocardial metabolism have recently attracted attention. They have the potential to relieve symptoms in patients with refractory angina who are already on "optimal" medical therapy and have disease that is not amenable to revascularisation, making these drugs an attractive addition to therapy, particularly for the elderly population. In some cases, they may even be used as first-line treatment. These drugs increase glucose metabolism at the expense of free-fatty-acid metabolism, enhancing oxygen efficiency during myocardial ischaemia. Whilst they have been demonstrated to reduce ischaemia in several clinical trials, their use remains limited. This review aims to draw attention to these "metabolic" antianginal drugs while surveying the evidence supporting their use and mode of action. Four metabolic antianginal drugs are reviewed: perhexiline, trimetazidine, ranolazine, and etomoxir. We also discuss the metabolic actions of glucose-insulin-potassium and beta-blockers and describe myocardial metabolism during normal and ischaemic conditions. The potential of these metabolic agents may extend beyond the treatment of ischaemia secondary to coronary artery disease. They offer significant promise for the treatment of symptoms occurring due to inoperable aortic stenosis, hypertrophic cardiomyopathy, and chronic heart failure.