Neuberg Gerald W, Miller Alan B, O'Connor Chris M, Belkin Robert N, Carson Peter E, Cropp Anne B, Frid David J, Nye Regina G, Pressler Milton L, Wertheimer John H, Packer Milton
Division of Circulatory Physiology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Am Heart J. 2002 Jul;144(1):31-8. doi: 10.1067/mhj.2002.123144.
In patients with chronic heart failure (CHF), diuretic requirements increase as the disease progresses. Because diuretic resistance can be overcome with escalating doses, the evaluation of CHF severity and prognosis may be incomplete without considering the intensity of therapy.
The prognostic importance of diuretic resistance (as evidenced by a high-dose requirement) was retrospectively evaluated in 1153 patients with advanced CHF who were enrolled in the Prospective Randomized Amlodipine Survival Evaluation (PRAISE). The relation of loop diuretic and angiotensin-converting enzyme inhibitor doses (defined by their median values) and other baseline characteristics to total and cause-specific mortality was determined by proportion hazards regression.
High diuretic doses were independently associated with mortality, sudden death, and pump failure death (adjusted hazard ratios [HRs] 1.37 [P =.004], 1.39 [P =.042], and 1.51 [P =.034], respectively). Use of metolazone was an independent predictor of total mortality (adjusted HR = 1.37, P =.016) but not of cause-specific mortality. Low angiotensin-converting enzyme inhibitor dose was an independent predictor of pump failure death (adjusted HR = 2.21, P =.0005). Unadjusted mortality risks of congestion and its treatment were additive and comparable to those of established risk factors.
The independent association of high diuretic doses with mortality suggests that diuretic resistance should be considered an indicator of prognosis in patients with chronic CHF. These retrospective observations do not establish harm or rule out a long-term benefit of diuretics in CHF, because selection bias may entirely explain the relation of prescribed therapy to death.
在慢性心力衰竭（CHF）患者中，随着疾病进展，利尿剂需求增加。由于利尿剂抵抗可通过增加剂量来克服，因此在不考虑治疗强度的情况下，对CHF严重程度和预后的评估可能不完整。
对纳入前瞻性随机氨氯地平生存评估（PRAISE）研究的1153例晚期CHF患者，回顾性评估利尿剂抵抗（以高剂量需求为证据）的预后重要性。通过比例风险回归确定袢利尿剂和血管紧张素转换酶抑制剂剂量（由其中位数定义）以及其他基线特征与全因死亡率和特定病因死亡率的关系。
高剂量利尿剂与死亡率、心源性猝死和泵衰竭死亡独立相关（校正风险比[HRs]分别为1.37[P = 0.004]、1.39[P = 0.042]和1.51[P = 0.034]）。使用美托拉宗是全因死亡率的独立预测因素（校正HR = 1.37，P = 0.016），但不是特定病因死亡率的预测因素。低剂量血管紧张素转换酶抑制剂是泵衰竭死亡的独立预测因素（校正HR = 2.21，P = 0.0005）。充血及其治疗的未校正死亡风险具有相加性，且与既定风险因素的风险相当。
高剂量利尿剂与死亡率的独立关联表明，利尿剂抵抗应被视为慢性CHF患者预后的一个指标。这些回顾性观察结果并未证实利尿剂对CHF有害或排除其长期益处，因为选择偏倚可能完全解释了所开治疗与死亡之间的关系。
