Ostergren Jan B
Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.
J Hypertens Suppl. 2006 Mar;24(1):S3-7. doi: 10.1097/01.hjh.0000220400.08128.fa.
Randomized clinical trials in patients with chronic heart failure and reduced left ventricular ejection fraction (LVEF) have demonstrated the life-saving and symptomatic benefits of angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and, in more selected patients, spironolactone. Despite these major advancements, the prevalence of heart failure continues to increase mainly as a consequence of aging populations. The development of angiotensin II type 1 receptor blockers (ARBs) provides a pharmacologically distinct mechanism of inhibiting the renin-angiotensin-aldosterone system. ARBs offer the potential to produce further clinical improvements for patients with heart failure above and beyond ACE inhibitors, as well as an alternative for those intolerant to an ACE inhibitor.
The Candesartan in Heart failure--Assessment of Reduction in Mortality and morbidity (CHARM) programme was designed as three parallel, randomized, double-blind, placebo-controlled clinical trials comparing candesartan with placebo in three different but complementary populations of patients with symptomatic heart failure.
In patients with intolerance to an ACE inhibitor and an LVEF of 40% or less (the CHARM-Alternative trial), candesartan reduced cardiovascular mortality and hospitalizations for heart failure by 23% (P < 0.001). In patients with an LVEF of 40% or less treated with an ACE inhibitor (the CHARM-Added trial), candesartan reduced cardiovascular death and hospitalization for chronic heart failure by 15% (P = 0.011). In patients with a LVEF greater than 40% (the CHARM-Preserved trial), hospitalizations for heart failure and new-onset diabetes were significantly reduced.
The CHARM programme, together with evidence from mechanistic studies and from other large trials with ARBs, constitutes a firm basis for including an ARB in the therapeutic arsenal in the treatment for chronic heart failure.
针对慢性心力衰竭且左心室射血分数（LVEF）降低的患者开展的随机临床试验已证明，血管紧张素转换酶（ACE）抑制剂、β受体阻滞剂以及在部分特定患者中使用的螺内酯具有挽救生命和缓解症状的益处。尽管取得了这些重大进展，但心力衰竭的患病率仍在持续上升，主要原因是人口老龄化。血管紧张素II 1型受体阻滞剂（ARB）的研发提供了一种药理学上不同的抑制肾素 - 血管紧张素 - 醛固酮系统的机制。ARB有可能为心力衰竭患者带来超出ACE抑制剂的进一步临床改善，同时也为那些不能耐受ACE抑制剂的患者提供了一种替代药物。
心力衰竭中坎地沙坦——死亡率和发病率降低评估（CHARM）项目设计为三项平行、随机、双盲、安慰剂对照的临床试验，在三组不同但互补的有症状心力衰竭患者群体中比较坎地沙坦与安慰剂。
在不能耐受ACE抑制剂且LVEF为40%或更低的患者中（CHARM替代试验），坎地沙坦使心血管死亡率和因心力衰竭住院率降低了23%（P<0.001）。在接受ACE抑制剂治疗且LVEF为40%或更低的患者中（CHARM加用试验），坎地沙坦使慢性心力衰竭的心血管死亡和住院率降低了15%（P = 0.011）。在LVEF大于40%的患者中（CHARM保留试验），心力衰竭住院率和新发糖尿病显著降低。
CHARM项目，连同机制研究和其他ARB大型试验的证据，为将ARB纳入慢性心力衰竭治疗的药物库奠定了坚实基础。
