EFFECT OF VALSARTAN IN PATIENTS WITH STABLE, CHRONIC CONGESTIVE HEART FAILURE

对心力衰竭患者肾素-血管紧张素系统(RAS)的刺激会导致血管收缩、钠和容量滞留、去甲肾上腺素释放和心肌肥厚。血管紧张素转换酶(ACE)抑制剂阻断血管紧张素II(Ang II)的形成并抑制这些有害作用。尽管在心力衰竭患者中使用血管紧张素转换酶抑制剂进行有效的药物治疗，但死亡率仍然很高。Valsartan(CGP48933)是一种口服有效的Ang II受体拮抗剂。在血管紧张素转换酶II受体的单独水平上或与血管紧张素转换酶抑制联合应用时，更特异、更彻底地抑制RAS应该会带来更多的临床益处。在纽约心脏协会II-IV级心力衰竭患者中使用Valsartan进行的两项II期研究表明，与安慰剂相比，Valsartan在心脏血流动力学方面产生了统计上的显著改善。在对高血压患者的研究中，Valsartan也被证明可以将血压降低到与其他降压药相似的水平，具有更有利的耐受性。这项安慰剂对照试验有两个主要目标：1)评估在接受血管紧张素转换酶抑制剂治疗和禁止使用血管紧张素转换酶抑制剂的患者中，Valsartan对稳定性慢性NYHA II-IV级心力衰竭患者的发病率和死亡率的影响；2)确定Valsartan对心力衰竭症状和体征以及生活质量的影响。

Stimulation of the Renin-Angiotensin System (RAS) in patients with heart failure causes vasoconstriction, sodium and volume retention, norepinephrine release, and cardiac hypertrophy. Angiotensi converting enzyme (ACE) inhibitors block the formation of angiotensin II (Ang II) and suppress these deleterious effects. Despite this effective pharmacological therapy with ACE inhibitors in patients with heart failure, mortality remains high. Valsartan (CGP48933) is an orally active, potent Ang II receptor antagonist. A more specific and complete inhibition of the RAS, either at the level of the Ang II receptor alone, or in combination with ACE inhibition should provide further clinical benefit. Two Phase II studies with Valsartan in New York Heart Association Class II-IV heart failure patients showed that Valsartan produced statistically significant improvements in cardiac hemodynamics compared to placebo. In studies of hypertensives, Valsartan also has been shown to decrease blood pressure to a level similar to other antihypertensive medications, with a more favorable tolerability profile. There are two primary objectives of this placebo-controlled trial; 1) to asses the effect of Valsartan on morbidity and mortality in patients with stable, chronic NYHA Class II-IV heart failure both in patients receiving ACE inhibitors and in those patients where ACE inhibitors are contraindicated, 2) to determine the effect of Valsartan on signs and symptoms of heart failure and quality of life.