Lee Leong, Horowitz John, Frenneaux Michael
Wales Heart Research Institute, Heath Park, Cardiff, CF14 4XN, UK.
Eur Heart J. 2004 Apr;25(8):634-41. doi: 10.1016/j.ehj.2004.02.018.
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.
主要通过改变心肌代谢发挥抗缺血作用的抗心绞痛药物近来受到了关注。它们有可能缓解那些已经接受“最佳”药物治疗但仍患有难治性心绞痛且病情不适于血运重建的患者的症状，这使得这些药物成为治疗方案中颇具吸引力的补充，尤其对于老年人群体。在某些情况下，它们甚至可用作一线治疗。这些药物以游离脂肪酸代谢为代价增加葡萄糖代谢，在心肌缺血期间提高氧利用效率。虽然它们在多项临床试验中已被证明可减轻缺血，但它们的使用仍然有限。本综述旨在在审视支持其使用及作用方式的证据的同时，让人们关注这些“代谢性”抗心绞痛药物。对四种代谢性抗心绞痛药物进行了综述：哌克昔林、曲美他嗪、雷诺嗪和依托莫西。我们还讨论了葡萄糖 - 胰岛素 - 钾和β受体阻滞剂的代谢作用，并描述了正常和缺血状态下的心肌代谢。这些代谢药物的潜力可能超出对冠状动脉疾病继发缺血的治疗范围。它们为治疗因无法手术的主动脉瓣狭窄、肥厚型心肌病和慢性心力衰竭而出现的症状带来了巨大希望。
