Konstam Marvin A, Neaton James D, Dickstein Kenneth, Drexler Helmut, Komajda Michel, Martinez Felipe A, Riegger Gunter A J, Malbecq William, Smith Ronald D, Guptha Soneil, Poole-Wilson Philip A
Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA.
Lancet. 2009 Nov 28;374(9704):1840-8. doi: 10.1016/S0140-6736(09)61913-9. Epub 2009 Nov 16.
Angiotensin-receptor blockers (ARBs) are effective treatments for patients with heart failure, but the relation between dose and clinical outcomes has not been explored. We compared the effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure.
This double-blind trial was undertaken in 255 sites in 30 countries. 3846 patients with heart failure of New York Heart Association class II-IV, left-ventricular ejection fraction 40% or less, and intolerance to angiotensin-converting-enzyme (ACE) inhibitors were randomly assigned to losartan 150 mg (n=1927) or 50 mg daily (n=1919). Allocation was by block randomisation stratified by centre and presence or absence of beta-blocker therapy, and all patients and investigators were masked to assignment. The primary endpoint was death or admission for heart failure. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00090259.
Six patients in each group were excluded because of poor data quality. With 4.7-year median follow-up in each group (IQR 3.7-5.5 for losartan 150 mg; 3.4-5.5 for losartan 50 mg), 828 (43%) patients in the 150 mg group versus 889 (46%) in the 50 mg group died or were admitted for heart failure (hazard ratio [HR] 0.90, 95% CI 0.82-0.99; p=0.027). For the two primary endpoint components, 635 patients in the 150 mg group versus 665 in the 50 mg group died (HR 0.94, 95% CI 0.84-1.04; p=0.24), and 450 versus 503 patients were admitted for heart failure (0.87, 0.76-0.98; p=0.025). Renal impairment (n=454 vs 317), hypotension (203 vs 145), and hyperkalaemia (195 vs 131) were more common in the 150 mg group than in the 50 mg group, but these adverse events did not lead to significantly more treatment discontinuations in the 150 mg group.
Losartan 150 mg daily reduced the rate of death or admission for heart failure in patients with heart failure, reduced left-ventricular ejection fraction, and intolerance to ACE inhibitors compared with losartan 50 mg daily. These findings show the value of up-titrating ARB doses to confer clinical benefit.
Merck (USA).
血管紧张素受体阻滞剂（ARBs）是治疗心力衰竭患者的有效药物，但剂量与临床结局之间的关系尚未得到探讨。我们比较了高剂量与低剂量氯沙坦对心力衰竭患者临床结局的影响。
这项双盲试验在30个国家的255个地点进行。3846例纽约心脏病协会II-IV级心力衰竭、左心室射血分数40%或更低且不耐受血管紧张素转换酶（ACE）抑制剂的患者被随机分配至氯沙坦150mg组（n=1927）或每日50mg组（n=1919）。分配采用按中心以及是否接受β受体阻滞剂治疗分层的区组随机化，所有患者和研究人员均对分组情况不知情。主要终点为死亡或因心力衰竭入院。分析采用意向性治疗。本研究已在ClinicalTrials.gov注册，编号为NCT00090259。
每组各有6例患者因数据质量差被排除。每组中位随访4.7年（氯沙坦150mg组IQR为3.7-5.5；氯沙坦50mg组为3.4-5.5），150mg组有828例（43%）患者死亡或因心力衰竭入院，50mg组为889例（46%）（风险比[HR]0.90，95%CI 0.82-0.99；p=0.027）。对于两个主要终点组分，150mg组有635例患者死亡，50mg组为665例（HR 0.94，95%CI 0.84-1.04；p=0.24），因心力衰竭入院的患者分别为450例和503例（HR 0.87，95%CI 0.76-0.98；p=0.025）。150mg组的肾功能损害（n=454 vs 317）、低血压（203 vs 145）和高钾血症（195 vs 131）比50mg组更常见，但这些不良事件并未导致150mg组更多的治疗中断。
与每日50mg氯沙坦相比，每日150mg氯沙坦可降低心力衰竭、左心室射血分数降低且不耐受ACE抑制剂患者的死亡或因心力衰竭入院率。这些发现表明上调ARB剂量以获得临床益处的价值。
默克公司（美国）。
