Hradec J
III. interní klinika 1. lékarské fakulty UK a VFN Praha.
Vnitr Lek. 2009 Sep;55(9):802-7.
Two clinical trials--CORONA and GISSI-HF--have been conducted to resolve uncertainties about the effects of statins in patients with chronic heart failure and justified suspicions that treatment with statins in these patients might be detrimental. The CORONA trial researched the effects of 10 mg rosuvastatin compared to placebo on the incidence of serious cardiovascular events in 5,011 patients with systolic heart failure of ischemic aetiology, above 60 years of age and in the NYHA functional class II-IV. Even though rosuvastatin reduced the mean LDL-cholesterol plasma concentrations by 45.0% (p < 0.001) and high-sensitivity C-reactive protein (hsCRP) concentrations by 37.1% (p < 0.001), the incidence of cardiovascular events was not importantly affected (HR = 0.92; p = 0.12). Rosuvastatin had no effect on overall mortality. The treatment resulted only in a reduction of the number of hospitalizations for cardiovascular causes (p < 0.001). The GISSI-HF trial involved 4,574 patients with chronic heart failure irrespective of aetiology and the ejection fraction value randomised to take either 10 mg of rosuvastatin or placebo. The results were almost identical. Rosuvastatin had no effect on the incidence of the primary end-point--the sum of cardiovascular mortality and hospitalizations (HR = 1.01; p = 0.903). The overall mortality was not affected either. Administration of rosuvastatin in both studies was safe, the number of adverse events, including myopathies and renal failure, was no different from placebo. However, recent results from the CORONA trial subtrials have suggested that important interactions exist in patients with chronic heart failure between the effects of rosuvastatin and natriuretic peptide and hsCRP plasma concentrations. Rosuvastatin provides clinical benefit in patients with relatively low concentrations of natriuretic peptides, i.e. relatively well-controlled, while it has no clinical effect in patients with high natriuretic peptide concentrations. Similarly, rosuvastatin provides clinical benefit in patients with high hsCRP but has no effect in patients with normal hsCRP (< 2 mg/l).
已经开展了两项临床试验——CORONA试验和GISSI-HF试验,以解决关于他汀类药物对慢性心力衰竭患者影响的不确定性,并澄清对这些患者使用他汀类药物治疗可能有害的怀疑。CORONA试验研究了10毫克瑞舒伐他汀与安慰剂相比,对5011例年龄超过60岁、缺血性病因导致的收缩性心力衰竭且纽约心脏协会(NYHA)心功能分级为II-IV级患者严重心血管事件发生率的影响。尽管瑞舒伐他汀使平均低密度脂蛋白胆固醇血浆浓度降低了45.0%(p<0.001),高敏C反应蛋白(hsCRP)浓度降低了37.1%(p<0.001),但心血管事件的发生率并未受到显著影响(风险比[HR]=0.92;p=0.12)。瑞舒伐他汀对总死亡率没有影响。该治疗仅导致心血管原因住院次数减少(p<0.001)。GISSI-HF试验纳入了4574例慢性心力衰竭患者,无论病因和射血分数值如何,随机分为服用10毫克瑞舒伐他汀或安慰剂两组。结果几乎相同。瑞舒伐他汀对主要终点事件——心血管死亡率和住院率之和——的发生率没有影响(HR=1.01;p=0.903)。总死亡率也未受影响。在两项研究中,服用瑞舒伐他汀都是安全的,不良事件(包括肌病和肾衰竭)的数量与安慰剂组没有差异。然而,CORONA试验子试验的最新结果表明,在慢性心力衰竭患者中,瑞舒伐他汀的作用与利钠肽和hsCRP血浆浓度之间存在重要的相互作用。瑞舒伐他汀在利钠肽浓度相对较低(即病情相对得到控制)的患者中具有临床益处,而在利钠肽浓度高的患者中没有临床效果。同样,瑞舒伐他汀在hsCRP浓度高的患者中具有临床益处,但在hsCRP正常(<2毫克/升)的患者中没有效果。