Taylor Anne L, Ziesche Susan, Yancy Clyde W, Carson Peter, Ferdinand Keith, Taylor Malcolm, Adams Kirkwood, Olukotun Adeoye Y, Ofili Elizabeth, Tam S William, Sabolinski Michael L, Worcel Manuel, Cohn Jay N
Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Circulation. 2007 Apr 3;115(13):1747-53. doi: 10.1161/CIRCULATIONAHA.106.644013. Epub 2007 Mar 19.
We previously reported that the fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride (FDC I/H) significantly decreased the risk of all-cause death and first hospitalization for heart failure (HF) and improved quality of life in patients with New York Heart Association class III or IV heart failure in the African-American Heart Failure Trial (A-HeFT). The current analyses further define the effect of FDC I/H on the timing of event-free survival (mortality or first hospitalization for HF) and time to first hospitalization for HF, as well as effects by subgroups and effects on cause-specific mortality.
Kaplan-Meier analyses of the 1050 A-HeFT patients on standard neurohormonal blockade demonstrated that FDC I/H produced a 37% improvement in event-free survival (P<0.001) and a 39% reduction in the risk for first hospitalization for HF (P<0.001). These benefits appeared to emerge early (at approximately 50 days of treatment) and were sustained through the duration of the trial. Subgroup analyses of treatment effect by age, sex, baseline blood pressure, history of chronic renal insufficiency, presence of diabetes mellitus, cause of HF, and baseline medication usage demonstrated consistent beneficial effect of FDC I/H on the primary composite score and event-free survival across all subgroups. Mortality from pump failure was reduced by 75% (P=0.012).
FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.
我们之前报道过，在非裔美国人心力衰竭试验（A-HeFT）中，固定剂量复方硝酸异山梨酯和盐酸肼屈嗪（FDC I/H）显著降低了全因死亡风险和首次因心力衰竭（HF）住院的风险，并改善了纽约心脏协会III或IV级心力衰竭患者的生活质量。当前分析进一步明确了FDC I/H对无事件生存期（死亡或首次因HF住院）时间以及首次因HF住院时间的影响，以及各亚组的影响和对特定病因死亡率的影响。
对1050例接受标准神经激素阻滞剂治疗的A-HeFT患者进行Kaplan-Meier分析表明，FDC I/H使无事件生存期改善了37%（P<0.001），首次因HF住院的风险降低了39%（P<0.001）。这些益处似乎在治疗约50天时就已出现，并在试验期间持续存在。按年龄、性别、基线血压、慢性肾功能不全病史、糖尿病的存在、HF病因和基线用药情况进行的治疗效果亚组分析表明，FDC I/H对所有亚组的主要复合评分和无事件生存期均有一致的有益影响。泵衰竭导致的死亡率降低了75%（P=0.012）。
在A-HeFT队列中，对正在服用神经激素阻滞剂的中度至重度HF黑人患者采用FDC I/H治疗，可使无事件生存期和因HF住院情况早期且持续得到显著改善，心血管和泵衰竭死亡导致的死亡率显著降低。治疗对主要复合终点和无事件生存期的影响在各亚组中是一致的。
