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CMAJ:糖尿病患者使用替米沙坦和缬沙坦并发心血管疾病风险较低

2013-07-18 fyc5078 dxy

一项大规模的回顾性研究显示,相比于厄贝沙坦,糖尿病患者使用血管紧张素受体阻滞剂(ARBs) 替米沙坦(美压定,勃林格殷格翰)和缬沙坦时,发生大血管疾病的风险要明显降低。分析表明,使用替米沙坦(Telmisartan)和缬沙坦(Valsartan)可使心肌梗死、中风或心衰的住院风险分别降低15%和14%。而使用氯沙坦(Losartan)和坎地沙坦(Candesartan)糖尿病患者的心血管事件发生率

一项大规模的回顾性研究显示,相比于厄贝沙坦,糖尿病患者使用血管紧张素受体阻滞剂(ARBs) 替米沙坦(美压定,勃林格殷格翰)和缬沙坦时,发生大血管疾病的风险要明显降低。分析表明,使用替米沙坦(Telmisartan)和缬沙坦(Valsartan)可使心肌梗死、中风或心衰的住院风险分别降低15%和14%。而使用氯沙坦(Losartan)和坎地沙坦(Candesartan)糖尿病患者的心血管事件发生率并没有明显降低。

托尼·安东尼奥(多伦多市圣米歇尔医院)及其同事在他们的报告中称:“研究结果显示,血管紧张素受体阻滞剂用于预防糖尿病相关的大血管疾病,其药物组间有效性具有重要的统计学差异,但在临床实践中用于此种用途时,可能差异并不明显。”该研究报告于2013年7月8日在线发表于加拿大医学协会期刊上。

鉴于这一结果,该研究小组认为,替米沙坦和缬沙坦“可能因此成为这些患者首选的血管紧张素受体阻滞剂。”研究人员在文章中分析道,替米沙坦有几个区别于其它血管紧张素受体阻滞剂的多效性属性。他们特别强调,替米沙坦是一种过氧化物酶体增殖因子激活受体(PPAR-γ)的部分激动剂。PPAR-γ 是一种配体激活的转录因子,用来调节脂类代谢和胰岛素敏感度。因为替米沙坦只是过氧化物酶体增殖因子激活受体的部分激动剂,所以没有完全激动剂的水钠潴留、水肿和心力衰竭等相关副作用。

纽约大学医学院的Sripal Bangalore博士没有参与这项研究,他认为这一研究结果令人深思。Bangalore说:“在临床上,我们大多数人认为血管紧张素受体阻滞剂作为一类药物其效果相似,但组间差异一直存有争论。我们已经表明,在所有血管紧张素受体阻滞剂中,氯沙坦的抗高血压效果最低。因此,从一个大型的观察性研究中看到这些数据证明替米沙坦和缬沙坦的可能优势是非常有趣的。”

54000多名患者入组进行分析

该项以人群为基础的回顾性研究对54186名加拿大糖尿病患者进行了分析,这些患者从2001年至2011年开始使用血管紧张素受体阻滞剂。所有患者年龄均为66岁以上,平均年龄73岁,罹患糖尿病平均时间约为6年。20.2%的患者接受坎地沙坦治疗,23.4%的患者接受厄贝沙坦治疗,15.5%的患者使用氯沙坦,15.1%的患者使用替米沙坦,25.8%的患者使用缬沙坦。

主要终点为因心肌梗死、心衰或中风而住院的一个复合终点,有2712名使用血管紧张素受体阻滞剂的患者出现终点事件。在调整的风险模型中,与厄贝沙坦相比,替米沙坦的主要终点风险降低了15%,缬沙坦的风险降低14%。在一项剂量反应分析中,研究小组发现,尽管调整剂量后缬沙坦的有效性有一定程度的减弱,但中等剂量与高剂量血管紧张素受体阻滞剂的主要结果风险没有差异。

因心肌梗死、中风或心衰住院的复合终点风险
Drug 
Adjusted hazard ratio (95% CI) 
Irbesartan 
1.00 (reference)
Telmisartan 
0.85 (0.74-0.97)
Candesartan 
0.99 (0.89-1.11)
Losartan 
0.93 (0.83-1.05)
Valsartan 
0.86 (0.77-0.96)

降低主要终点风险主要在于降低心衰住院风险。单独分析,替米沙坦的心衰住院风险下降20%,而缬沙坦下降13%,位于无显著差异的临界值。(风险比 0.87;95% CI 0.75-1.00)。

Bangalore认为,该研究的优势在于患者样本量大。如此大的样本量不可能在头对头比较不同血管紧张素受体阻滞剂的大规模随机临床试验中复制出来。但对种于这种观察性分析,其劣势是可能出现混淆及选择确定偏差。他指出,研究主要终点在于心衰住院率的下降,但在基线处只有6.3%的替米沙坦治疗患者及7.1%的缬沙坦治疗患者出现充血性心力衰竭,而洛沙坦治疗患者则为9.0%。

“无论怎样,这些结果是令人鼓舞的。”Bangalore这样说。

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    2014-05-24 丁鹏鹏
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