Effects of the Oral Direct Renin Inhibitor Aliskiren in Patients With Symptomatic Heart Failure
Effects of the Oral Direct Renin Inhibitor Aliskiren in Patients With Symptomatic Heart Failure
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DOI：
10.1161/circheartfailure.107.740704
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发表时间：
2008-05-01
影响因子：
9.7
通讯作者：
Lewsey, Jim
中科院分区：
文献类型：
--
作者：
McMurray, John J. V.;Pitt, Bertram;Lewsey, Jim
背景：在使用血管紧张素转换酶（ACE）抑制剂进行慢性治疗期间，肾素释放负反馈抑制的丧失导致肾素分泌和肾素-血管紧张素-醛固酮（RAAS）级联下游成分的代偿性增加。这可能克服ACE抑制，但应通过直接肾素抑制剂阻断。我们研究了直接肾素抑制剂阿利斯基伦加ACE抑制剂对心力衰竭患者的影响。方法和结果：患有纽约心脏协会II至IV级心力衰竭、目前或既往高血压病史、血浆脑利钠肽（BNP）浓度为bbb100 pg/mL且已接受ACE抑制剂（或血管紧张素受体阻滞剂）和p受体阻滞剂治疗的患者随机分为安慰剂（n=146）或aliskiren 150mg /d （n=156）治疗3个月。主要疗效指标为n端亲bnp （NT-proBNP）的治疗间差异。患者的平均年龄为68岁，平均射血分数为31%，平均+/- SD收缩压为129 +/- 17.4 mm Hg。62%的患者属于纽约心脏协会功能II级，33%的患者正在服用醛固酮拮抗剂。安慰剂组血浆NT-proBNP升高762 +/- 6123 pg/mL， aliskiren组血浆NT-proBNP下降24245pg /mL （P=0.0106）。aliskiren也降低了BNP和尿醛固酮（但不是血浆）。在临床上，阿利克伦和安慰剂在血压和生化指标上没有显著差异。结论：阿利克伦联合ACE抑制剂（或血管紧张素受体阻滞剂）和β受体阻滞剂治疗心力衰竭具有良好的神经体液作用，且耐受性良好。（中国心脏杂志。2008;1:17-24）
Background-Loss of negative feedback inhibition of renin release during chronic treatment with an angiotensin-converting enzyme (ACE) inhibitor leads to a compensatory rise in renin secretion and downstream components of the renin-angiotensin-aldosterone (RAAS) cascade. This may overcome ACE inhibition but should be blocked by a direct renin inhibitor. We studied the effects of adding the direct renin inhibitor aliskiren to an ACE inhibitor in patients with heart failure.Methods and Results-Patients with New York Heart Association class II to IV heart failure, current or past history of hypertension, and plasma brain natriuretic peptide (BNP) concentration > 100 pg/mL who had been treated with an ACE inhibitor (or angiotensin receptor blocker) and P-blocker were randomized to 3 months of treatment with placebo (n=146) or aliskiren 150 mg/d (n=156). The primary efficacy outcome was the between-treatment difference in N-terminal pro-BNP (NT-proBNP). Patients' mean age was 68 years, mean ejection fraction was 31%, and mean +/- SD systolic blood pressure was 129 +/- 17.4 mm Hg. Sixty-two percent of the patients were in New York Heart Association functional class II, and 33% were taking an aldosterone antagonist. Plasma NT-proBNP rose by 762 +/- 6123 pg/mL with placebo and fell by 244 2025 pg/mL with aliskiren (P=0.0106). BNP and urinary (but not plasma) aldosterone were also reduced by aliskiren. Clinically important differences in blood pressure and biochemistry were not seen between aliskiren and placebo.Conclusions-Addition of aliskiren to an ACE inhibitor (or angiotensin receptor blocker) and beta-blocker had favorable neurohumoral effects in heart failure and appeared to be well tolerated. (Circ Heart Fail. 2008;1:17-24.)