Taylor Anne L
Division of Cardiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Am J Cardiol. 2005 Oct 10;96(7B):44-8. doi: 10.1016/j.amjcard.2005.07.033. Epub 2005 Aug 9.
Progressive vascular and myocardial remodeling in heart failure is effectively slowed by therapy with neurohormonal antagonists, including angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, aldosterone antagonists, and adrenergic-receptor blockers. These therapies, along with the correction of hemodynamic abnormalities, have dramatically reduced morbidity and mortality in patients with heart failure. Endothelial dysfunction, increased oxidative stress, and decreased bioavailability of nitric oxide (NO) also occur in heart failure. Data suggest that endothelial dysfunction and reduced NO bioavailability may be more prevalent in populations who self-identify as African Americans. Thus, differences observed in the African American population with respect to prevalence of heart failure, etiology, outcomes, and response to medication may in part be explained by differences in the relative contributions of neurohormonal activation and diminished NO bioavailability to the progression of heart failure. The African American Heart Failure Trial (A-HeFT) was designed to assess the benefit of fixed-dose combination isosorbide dinitrate-hydralazine (ISDN-HYD) in an African American population with advanced heart failure. The A-HeFT enrolled 1,050 African American patients with New York Heart Association (NYHA) class III-IV heart failure with dilated ventricles and low ejection fractions. Patients were randomized to receive either a fixed-dose combination of ISDN-HYD or placebo added to standard neurohormonal blockade. The primary end point was a composite score in which mortality, hospitalization, and quality of life were weighted. On July 19, 2004, the independent Data Safety Monitoring Committee recommended early termination of the trial because of a significant mortality benefit in the cohort receiving fixed-dose ISDN-HYD. The A-HeFT confirms the benefit of fixed-dose ISDN-HYD, which may enhance NO bioavailability in African American patients with NYHA class III-IV heart failure and suggests that NO-enhancing therapy is an effective new treatment strategy for heart failure. In addition, the A-HeFT affirms the critical importance of the inclusion of population subgroups in clinical trials both as a way to probe for pathophysiologic mechanisms of disease and to devise optimal treatment strategies. The rich and unique A-HeFT database will provide new opportunities to understand the pathophysiology and management of heart failure.
神经激素拮抗剂治疗可有效减缓心力衰竭中进行性血管和心肌重塑，这些拮抗剂包括血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂、醛固酮拮抗剂和肾上腺素能受体阻滞剂。这些治疗方法，连同血流动力学异常的纠正，已显著降低了心力衰竭患者的发病率和死亡率。心力衰竭时还会出现内皮功能障碍、氧化应激增加和一氧化氮（NO）生物利用度降低。数据表明，内皮功能障碍和NO生物利用度降低在自我认定为非裔美国人的人群中可能更为普遍。因此，在非裔美国人中观察到的心力衰竭患病率、病因、结局及对药物反应方面的差异，部分可能是由于神经激素激活和NO生物利用度降低在心力衰竭进展中的相对作用不同所致。非裔美国人心力衰竭试验（A-HeFT）旨在评估固定剂量硝酸异山梨酯-肼屈嗪（ISDN-HYD）联合用药对晚期心力衰竭非裔美国人的益处。A-HeFT纳入了1050例纽约心脏病协会（NYHA）心功能III-IV级、心室扩张且射血分数低的非裔美国心力衰竭患者。患者被随机分为接受固定剂量ISDN-HYD联合用药或在标准神经激素阻滞剂基础上加用安慰剂。主要终点是一个综合评分，其中死亡率、住院率和生活质量都被纳入考量。2004年7月19日，独立数据安全监测委员会建议提前终止该试验，因为接受固定剂量ISDN-HYD的队列有显著的死亡率获益。A-HeFT证实了固定剂量ISDN-HYD的益处，这可能会提高NYHA心功能III-IV级非裔美国心力衰竭患者的NO生物利用度，并表明增强NO的治疗是心力衰竭一种有效的新治疗策略。此外，A-HeFT肯定了在临床试验中纳入人群亚组的至关重要性，这既是探究疾病病理生理机制的一种方式，也是制定最佳治疗策略的途径。丰富而独特的A-HeFT数据库将为理解心力衰竭的病理生理和管理提供新机会。
