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

心衰患者肾素-血管紧张素系统（RAS）的刺激导致血管收缩、钠和容量潴留、去甲肾上腺素释放和心脏肥厚。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。尽管使用ACE抑制剂对心力衰竭患者进行有效的药物治疗，但死亡率仍然很高。缬沙坦（CGP48933）是一种口服有效的Ang II受体拮抗剂。更具体和完全的RAS抑制，无论是单独在Ang II受体水平上，还是与ACE抑制联合，都将提供进一步的临床益处。两项在纽约心脏协会II- iv类心力衰竭患者中使用缬沙坦的II期研究表明，与安慰剂相比，缬沙坦在心脏血流动力学方面具有统计学意义的改善。在高血压的研究中，缬沙坦也被证明可以将血压降低到与其他降压药相似的水平，并且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)评估缬沙坦对稳定、慢性NYHA II-IV类心衰患者的发病率和死亡率的影响，包括接受ACE抑制剂治疗的患者和ACE抑制剂禁忌症患者；2)确定缬沙坦对心衰体征和症状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.