Baruch L, Anand I, Cohen I S, Ziesche S, Judd D, Cohn J N
Cardiology Section, Veterans Affairs Medical Center, Bronx, NY, USA.
Circulation. 1999 May 25;99(20):2658-64. doi: 10.1161/01.cir.99.20.2658.
ACE inhibitors may not adequately suppress deleterious levels of angiotensin II in patients with heart failure. An angiotensin receptor blocker added to an ACE inhibitor may exert additional beneficial effects.
Eighty-three symptomatic stable patients with chronic heart failure receiving long-term ACE inhibitor therapy were randomly assigned to double-blind treatment with valsartan 80 mg BID, valsartan 160 mg BID, or placebo while receiving their usual ACE inhibitor therapy. Studies were performed before and after the first dose of the test drug and again after 4 weeks of therapy. A single dose of lisinopril was administered during study days to ensure sustained ACE inhibition. Compared with placebo, the first dose of valsartan 160 mg resulted in a significantly greater reduction in pulmonary capillary wedge pressure at 3, 4, and 8 hours and during the prespecified 4- to 8-hour interval after the dose and in systolic blood pressure at 2, 3, 6, 8, and 12 hours and 4 to 8 hours after the dose. A pressure reduction from valsartan 80 mg did not achieve statistical significance. After 4 weeks of therapy, net reductions in 0-hour trough pulmonary capillary wedge pressure (-4.3 mm Hg; P=0. 16), pulmonary artery diastolic pressure (-4.7 mm Hg; P=0.013), and systolic blood pressure (-6.8 mm Hg; P=0.013) were observed in the valsartan 160 mg group compared with placebo. After 4 weeks of therapy, plasma aldosterone was reduced by valsartan 80 mg BID (-52. 1 pg/mL; P=0.001) and 160 mg BID (-47.8 pg/mL; P<0.001) compared with placebo, and there was a trend for a reduction in plasma norepinephrine (-97 pg/mL; P=0.10). Seventy-four of the 83 patients completed the trial.
Physiologically active levels of angiotensin II persist during standard long-term ACE inhibitor therapy.
在心力衰竭患者中，血管紧张素转换酶（ACE）抑制剂可能无法充分抑制有害水平的血管紧张素II。在ACE抑制剂基础上加用血管紧张素受体阻滞剂可能会产生额外的有益效果。
83例接受长期ACE抑制剂治疗的有症状的慢性心力衰竭稳定患者，在继续接受常规ACE抑制剂治疗的同时，被随机分配接受缬沙坦80mg每日两次、缬沙坦160mg每日两次或安慰剂的双盲治疗。在给予试验药物的首剂之前和之后以及治疗4周后进行研究。在研究期间给予单剂量赖诺普利以确保持续抑制ACE。与安慰剂相比，首剂缬沙坦160mg在给药后3、4和8小时以及预先设定的给药后4至8小时间隔内，肺毛细血管楔压显著降低，在给药后2、3、6、8和12小时以及4至8小时收缩压显著降低。缬沙坦80mg引起的血压降低未达到统计学显著性。治疗4周后，与安慰剂相比，缬沙坦160mg组0小时谷值肺毛细血管楔压净降低（-4.3mmHg；P = 0.16）、肺动脉舒张压净降低（-4.7mmHg；P = 0.013）和收缩压净降低（-6.8mmHg；P = 0.013）。治疗4周后，与安慰剂相比，缬沙坦80mg每日两次（-52.1pg/mL；P = 0.001）和缬沙坦160mg每日两次（-47.8pg/mL；P<0.001）可降低血浆醛固酮，血浆去甲肾上腺素也有降低趋势（-97pg/mL；P = 0.10）。83例患者中有74例完成了试验。
在标准的长期ACE抑制剂治疗期间，血管紧张素II的生理活性水平持续存在。
