Volz Elizabeth M, Felker G Michael
Division of Cardiology, Duke University School of Medicine, 2400 Pratt Street, Room 0311 Terrace Level, Durham, NC 27705, USA.
Curr Treat Options Cardiovasc Med. 2009 Dec;11(6):426-32. doi: 10.1007/s11936-009-0045-1.
Systemic and pulmonary congestion is a central aspect of both acute and chronic heart failure and directly leads to many of the clinical manifestations of these syndromes. Therefore, diuretic therapy to treat congestion plays a fundamental role in heart failure management. However, although diuretics are the most common drugs prescribed for heart failure, there is limited quality evidence to guide their use. Unlike other components of the heart failure armamentarium, such as beta-blockers and angiotensin-converting enzyme inhibitors, diuretics (with the exception of aldosterone antagonists) have not been shown to decrease heart failure progression or improve mortality. Additionally, some observational data suggest that diuretics may actually be harmful in heart failure, contributing to neurohormonal activation, renal dysfunction, and potentially mortality. Despite these concerns, diuretics remain ubiquitous in heart failure management because of the need to address symptoms of congestion and the lack of alternative strategies. Recently, the development of a variety of potential adjuncts or alternatives to diuretic therapy has suggested the need for an active reappraisal of diuretic therapy for heart failure. The main classes of diuretics are the loop diuretics, potassium-sparing diuretics, and thiazides. Loop diuretics, the mainstay of acute and chronic therapy for heart failure, are "threshold drugs"; therefore, an adequate dose to achieve a pharmacodynamic effect (ie, to increase urine output) must be prescribed for effective therapy. The minimum dose to achieve diuresis and manage congestion should be used to minimize adverse effects. For patients refractory to initial dosing of intravenous diuretics, options include dose escalation, use of continuous infusion rather than intermittent boluses, or combination therapy with the addition of a thiazide or thiazide-like diuretic (eg, metolazone). Management of chronic heart failure often includes patient-directed titration of diuretics based on changes in symptoms or body weight in an attempt to decrease hospitalizations, although the efficacy of this strategy has not been tested in well-designed trials. Aldosterone antagonists, which are used primarily as neurohormonal agents rather than for their diuretic effects, are indicated for patients with systolic failure and moderate to severe symptoms, as long as renal function and serum potassium are stable and monitored closely. All diuretic therapy requires careful monitoring of electrolytes and renal function. Whether newer modalities for managing congestion (vasopressin antagonists, adenosine A(1) antagonists, and ultrafiltration therapy) will be an improvement over diuretic therapy will be determined by the results of multiple ongoing clinical trials.
全身和肺部充血是急性和慢性心力衰竭的核心方面，直接导致这些综合征的许多临床表现。因此，治疗充血的利尿疗法在心力衰竭管理中起着至关重要的作用。然而，尽管利尿剂是治疗心力衰竭最常用的药物，但指导其使用的高质量证据有限。与心力衰竭治疗药物库中的其他成分（如β受体阻滞剂和血管紧张素转换酶抑制剂）不同，利尿剂（醛固酮拮抗剂除外）尚未被证明可降低心力衰竭进展或改善死亡率。此外，一些观察数据表明，利尿剂在心力衰竭中可能实际上是有害的，会导致神经激素激活、肾功能障碍，并可能导致死亡。尽管存在这些担忧，但由于需要解决充血症状且缺乏替代策略，利尿剂在心力衰竭管理中仍然普遍使用。最近，多种潜在的利尿剂治疗辅助药物或替代药物的开发表明，有必要对心力衰竭的利尿剂治疗进行积极的重新评估。利尿剂的主要类别是袢利尿剂、保钾利尿剂和噻嗪类利尿剂。袢利尿剂是急性和慢性心力衰竭治疗的主要药物，是“阈值药物”；因此，必须开出足够的剂量以达到药效学效果（即增加尿量）才能进行有效治疗。应使用实现利尿和控制充血的最小剂量以尽量减少不良反应。对于初始静脉注射利尿剂无效的患者，可选择增加剂量、采用持续输注而非间歇性推注，或联合使用噻嗪类或噻嗪样利尿剂（如美托拉宗）进行联合治疗。慢性心力衰竭的管理通常包括根据症状或体重变化由患者自行调整利尿剂剂量，以试图减少住院次数，尽管这一策略的疗效尚未在精心设计的试验中得到验证。醛固酮拮抗剂主要用作神经激素药物而非因其利尿作用，适用于收缩性心力衰竭且症状为中度至重度的患者，前提是肾功能和血清钾稳定并密切监测。所有利尿剂治疗都需要仔细监测电解质和肾功能。新型充血管理方法（加压素拮抗剂、腺苷A(1)拮抗剂和超滤治疗）是否会优于利尿剂治疗将由多项正在进行的临床试验结果来确定。
