Packer M, Poole-Wilson P A, Armstrong P W, Cleland J G, Horowitz J D, Massie B M, Rydén L, Thygesen K, Uretsky B F
College of Physicians and Surgeons (M.P.), Columbia University, New York, NY 10032, USA.
Circulation. 1999 Dec 7;100(23):2312-8. doi: 10.1161/01.cir.100.23.2312.
Angiotensin-converting enzyme (ACE) inhibitors are generally prescribed by physicians in doses lower than the large doses that have been shown to reduce morbidity and mortality in patients with heart failure. It is unclear, however, if low doses and high doses of ACE inhibitors have similar benefits.
We randomly assigned 3164 patients with New York Heart Association class II to IV heart failure and an ejection fraction < or = 30% to double-blind treatment with either low doses (2.5 to 5.0 mg daily, n=1596) or high doses (32.5 to 35 mg daily, n=1568) of the ACE inhibitor, lisinopril, for 39 to 58 months, while background therapy for heart failure was continued. When compared with the low-dose group, patients in the high-dose group had a nonsignificant 8% lower risk of death (P=0.128) but a significant 12% lower risk of death or hospitalization for any reason (P=0.002) and 24% fewer hospitalizations for heart failure (P=0.002). Dizziness and renal insufficiency was observed more frequently in the high-dose group, but the 2 groups were similar in the number of patients requiring discontinuation of the study medication. Conclusions-These findings indicate that patients with heart failure should not generally be maintained on very low doses of an ACE inhibitor (unless these are the only doses that can be tolerated) and suggest that the difference in efficacy between intermediate and high doses of an ACE inhibitor (if any) is likely to be very small.
医生通常给患者开具的血管紧张素转换酶（ACE）抑制剂剂量低于已证实可降低心力衰竭患者发病率和死亡率的大剂量。然而，低剂量和高剂量的ACE抑制剂是否具有相似的益处尚不清楚。
我们将3164例纽约心脏协会心功能II级至IV级、射血分数≤30%的心力衰竭患者随机分为两组，分别接受低剂量（每日2.5至5.0毫克，n = 1596）或高剂量（每日32.5至35毫克，n = 1568）的ACE抑制剂赖诺普利进行双盲治疗，为期39至58个月，同时继续进行心力衰竭的背景治疗。与低剂量组相比，高剂量组患者的死亡风险降低8%，差异无统计学意义（P = 0.128），但因任何原因导致的死亡或住院风险显著降低12%（P = 0.002），心力衰竭住院次数减少24%（P = 0.002）。高剂量组更频繁地观察到头晕和肾功能不全，但两组中需要停用研究药物的患者数量相似。结论——这些发现表明，心力衰竭患者一般不应长期使用非常低剂量的ACE抑制剂（除非这些是唯一能耐受的剂量），并提示ACE抑制剂中剂量和高剂量之间的疗效差异（如果有的话）可能非常小。
