Wood M A, Hess M L
Department of Medicine, Medical College of Virginia, Richmond 23298-0281.
Am J Med Sci. 1989 Feb;297(2):105-13. doi: 10.1097/00000441-198902000-00006.
The existing management of severe chronic congestive heart failure carries a dismal prognosis. Mortality over 6 months is 50% by some estimates. This fact, coupled with increasing concern for the safety and efficacy of the digitalis glycosides, has stimulated an intense search for new oral cardiotonic agents suitable for chronic administration. Despite the ability of many phosphodiesterase inhibiting agents to affect profound hemodynamic improvements acutely after oral or intravenous administration, none of the four agents here reviewed in 30 clinical trials has been adequately proven to provide benefit over conventional long-term therapy of severe heart failure. The four drugs to have undergone long-term clinical trials are amrinone, milrinone, enoximone (MDL 17043), and piroximone (MDL 19,025). For amrinone, inefficacy was revealed through carefully designed, placebo-controlled studies despite initial enthusiasm generated by open uncontrolled trials. Enoximone has suffered rapid attenuation of its hemodynamic effectiveness in most studies, and piroximone failed in its only long-term trial. Therefore, final judgment on most of these agents must await completion of controlled clinical trials, and any initial optimism stimulated by the current uncontrolled studies should be met with reservation.
重度慢性充血性心力衰竭的现有治疗方法预后不佳。据一些估计，6个月内的死亡率为50%。这一事实，再加上对洋地黄苷安全性和有效性的日益关注，促使人们积极寻找适合长期服用的新型口服强心剂。尽管许多磷酸二酯酶抑制剂在口服或静脉给药后能迅速显著改善血流动力学，但在30项临床试验中，这里所综述的四种药物均未被充分证明比重度心力衰竭的传统长期治疗更具优势。已进行长期临床试验的四种药物是氨力农、米力农、依诺昔酮（MDL 17043）和匹罗昔酮（MDL 19025）。对于氨力农，尽管开放的非对照试验最初带来了热情，但通过精心设计的安慰剂对照研究发现其无效。在大多数研究中，依诺昔酮的血流动力学有效性迅速减弱，匹罗昔酮在其唯一的长期试验中失败。因此，对大多数这些药物的最终判断必须等待对照临床试验的完成，并且对于当前非对照研究所激发的任何初步乐观情绪都应持保留态度。
