Cleland John G F, Tendera Michal, Adamus Jerzy, Freemantle Nick, Polonski Lech, Taylor Jacqueline
Department of Cardiology, University of Hull, Castle Hill Hospital, Castle Road, Cottingham, Kingston upon Hull HU16 5JQ, UK.
Eur Heart J. 2006 Oct;27(19):2338-45. doi: 10.1093/eurheartj/ehl250. Epub 2006 Sep 8.
Many patients who receive a diagnosis of heart failure have neither a low left ventricular (LV) ejection fraction nor valve disease. Few substantial randomized controlled trials have been conducted in this population, none has focussed on patients with evidence of diastolic dysfunction and none has shown clear benefit on symptoms, morbidity, or mortality.
This was a randomized double-blind trial, comparing placebo with perindopril, 4 mg/day in patients aged > or =70 years with a diagnosis of heart failure, treated with diuretics and an echocardiogram suggesting diastolic dysfunction and excluding substantial LV systolic dysfunction or valve disease. The primary endpoint was a composite of all-cause mortality and unplanned heart failure related hospitalization with a minimum follow-up of 1 year. A total of 850 patients were randomized. Their mean age was 76 (SD 5) years and 55% were women. Median follow-up was 2.1 (IQR 1.5-2.8) years. Enrollment and event rates were lower than anticipated, reducing the power of the study to show a difference in the primary endpoint to 35%. Many patients withdrew from perindopril (28%) and placebo (26%) after 1 year and started taking open-label ACE-inhibitors. Overall, 107 patients assigned to placebo and 100 assigned to perindopril reached the primary endpoint (HR 0.919: 95% CI 0.700-1.208; P = 0.545). By 1 year, reductions in the primary outcome (HR 0.692: 95% CI 0.474-1.010; P = 0.055) and hospitalization for heart failure (HR 0.628: 95% CI 0.408-0.966; P = 0.033) were observed and functional class (P < 0.030) and 6-min corridor walk distance (P = 0.011) had improved in those assigned to perindopril.
Uncertainty remains about the effects of perindopril on long-term morbidity and mortality in this clinical setting since this study had insufficient power for its primary endpoint. However, improved symptoms and exercise capacity and fewer hospitalizations for heart failure in the first year were observed on perindopril, during which most patients were on assigned therapy, suggesting that it may be of benefit in this patient population.
许多被诊断为心力衰竭的患者既没有左心室（LV）射血分数降低，也没有瓣膜疾病。针对这一人群开展的大规模随机对照试验很少，没有一项试验聚焦于有舒张功能障碍证据的患者，也没有一项试验显示对症状、发病率或死亡率有明显益处。
这是一项随机双盲试验，比较安慰剂与培哚普利（4毫克/天）对年龄≥70岁、诊断为心力衰竭、接受利尿剂治疗且超声心动图提示舒张功能障碍、排除严重左心室收缩功能障碍或瓣膜疾病的患者的疗效。主要终点是全因死亡率和与心力衰竭相关的非计划住院的复合终点，最短随访1年。共有850名患者被随机分组。他们的平均年龄为76（标准差5）岁，55%为女性。中位随访时间为2.1（四分位间距1.5 - 2.8）年。入组率和事件发生率低于预期，使研究显示主要终点差异的效能降至35%。许多患者在1年后退出培哚普利组（28%）和安慰剂组（26%），开始服用开放标签的血管紧张素转换酶抑制剂。总体而言，107名分配到安慰剂组的患者和100名分配到培哚普利组的患者达到了主要终点（风险比0.919：95%置信区间0.700 - 1.208；P = 0.545）。到1年时，观察到主要结局有所降低（风险比0.692：95%置信区间0.474 - 1.010；P = 0.055）以及心力衰竭住院率降低（风险比0.628：95%置信区间0.408 - 0.966；P = 0.033），且分配到培哚普利组的患者功能分级（P < 0.030）和6分钟走廊步行距离（P = 0.011）有所改善。
由于本研究对于其主要终点的效能不足，培哚普利在这种临床情况下对长期发病率和死亡率的影响仍不确定。然而，在第一年观察到培哚普利组患者症状改善、运动能力提高且心力衰竭住院次数减少，在此期间大多数患者接受分配的治疗，这表明培哚普利可能对该患者群体有益。
