JAMA：心衰病人服用高血压药物与死亡风险的增加没有关系

4月11日，国际杂志《美国医学会杂志》JAMA上的一项研究披露，尽管观察性的研究提示，氯沙坦这种主要用于治疗高血压的药物与同类药物（血管紧张素Ⅱ受体阻滞剂[ARBs]）中的其它药物相比可能与心衰患者死亡风险的增加有关，但一则包括了近6，500名患者的分析发现，总的来说，与ARB坎地沙坦的使用相比，氯沙坦的使用与全因死亡或心血管性死亡的增加无关。

丹麦哥本哈根Statens Serum研究所的Henrik Svanstrom， M.Sc.及其同事们开展了一项研究，旨在对氯沙坦的使用与坎地沙坦相比是否与心衰病人的全因死亡率的增加有关进行评估。该研究——它包括了来自一个丹麦全国性的登记档案数据——将个人水平的资讯进行了关联，这些资讯有医院联系、配了药的处方以及可能的混淆因素（即那些会影响结果的因子）。那些年龄在45岁及以上的在1998至2008年间因为心衰而首次入院的病人从该登记档案中被识别出来。氯沙坦和坎地沙坦的新的使用者被挑出来以纳入该研究群组。最终的研究群体中包括有6，479名患者，其中有2，082名坎地沙坦的服用者及4，397名氯沙坦的服用者。

在随访期间，该研究群体中有2，378人死亡。在这些死亡中，有330人的死亡发生在服用坎地沙坦的过程中，有1，212人的死亡发生在服用氯沙坦的过程中。研究人员发现，与坎地沙坦相比，服用氯沙坦与死亡风险的显著增加之间没有关系。此外，与坎地沙坦相比，服用氯沙坦与心血管性死亡增加的风险之间没有显著的关系。

文章的作者确实发现，与高剂量的坎地沙坦（16-32毫克）相比，服用低剂量的氯沙坦（12.5毫克）与死亡风险增加2倍以上有关系。50毫克的氯沙坦（中间剂量）的治疗也与较高的死亡风险有关。然而，较高的死亡风险与服用100毫克的氯沙坦（高剂量）没有关系。

研究人员得出结论：“这些发现不支持特定的ARBs在心衰病人中会有差别效应这一假说。”（生物谷Bioon.com）

doi:10.1001/jama.2012.452
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Association of Treatment With Losartan vs Candesartan and Mortality Among Patients With Heart Failure

Henrik Svanström, MSc; Björn Pasternak, MD, PhD; Anders Hviid, MSc, Dr Med Sci

Context The benefit of angiotensin II-receptor blockers (ARBs) in heart failure is thought to be a class effect, but no head-to-head randomized trials have compared individual ARBs. Results from observational studies suggest that losartan may be associated with increased mortality in patients with heart failure compared with other ARBs. Objective To assess the hypothesis that losartan use is associated with increased all-cause mortality in heart failure patients as compared with candesartan. Design, Setting, and Participants We conducted a nationwide Danish registry–based cohort study, linking individual-level information on hospital contacts, filled prescriptions, and potential confounders. Patients aged 45 years and older with first-time hospitalization for heart failure in 1998-2008 were identified from the Danish National Patient Registry. New users of losartan and candesartan were selected for inclusion in the study cohort. Main Outcome Measures We used Cox proportional hazards regression to compare the risk of all-cause mortality in users of losartan and candesartan. Results Among 4397 users of losartan, 1212 deaths occurred during 11 347 person-years of follow-up (unadjusted incidence rate [IR]/100 person-years, 10.7; 95% CI, 10.1-11.3) compared with 330 deaths during 3675 person-years among 2082 users of candesartan (unadjusted IR/100 person-years, 9.0; 95% CI, 8.1-10.0). Compared with candesartan, losartan was not associated with increased all-cause mortality (adjusted hazard ratio [HR], 1.10; 95% CI, 0.96-1.25) or cardiovascular mortality (adjusted HR, 1.14; 95% CI, 0.96-1.36). Compared with high doses of candesartan (16-32 mg), low-dose (12.5 mg) and medium-dose losartan (50 mg) were associated with increased mortality (HR, 2.79; 95% CI, 2.19-3.55 and HR, 1.39; 95% CI, 1.11-1.73, respectively); use of high-dose losartan (100 mg) was similar in risk (HR, 0.71; 95% CI, 0.50-1.00). Conclusions Among patients with heart failure, overall use of losartan compared with candesartan was not associated with an increased mortality risk. Although low doses of losartan were associated with increased mortality, there was no increased mortality comparing high-dose losartan against the highest doses of candesartan.