Chockalingam Anand, Venkatesan S, Subramaniam T, Jagannathan V, Elangovan S, Alagesan R, Gnanavelu G, Dorairajan Smrita, Krishna B P, Chockalingam V
Department of Cardiology, Madras Medical College and Research Institute, Chennai, India.
Am Heart J. 2004 Apr;147(4):E19. doi: 10.1016/j.ahj.2003.10.017.
Animal models have demonstrated a benefit of angiotensin-converting enzyme inhibitors (ACEI) in experimental aortic stenosis (AS), and intravenous nitroprusside has shown hemodynamic improvements in AS with left ventricular (LV) dysfunction. Although routinely used in most heart failure situations, ACEI are avoided in AS because of the risk of hypotension. We aimed to determine the clinical tolerance and efficacy of the ACEI enalapril in the setting of symptomatic severe AS.
Patients with symptomatic severe AS were enrolled in a randomized, double-blinded, controlled trial to enalapril or placebo arms after initial stabilization. Standard antifailure medications were continued. Enalapril was started at 2.5 mg bid and increased to 10 mg bid. The primary end points were development of hypotension and improvements in Borg dyspnea index and 6-minute walk distance at 1 month. Secondary end points were minor ACEI intolerance, cough, presyncope, improvement in New York Heart Association class, and echocardiographic parameters.
Fifty-six patients were enrolled (37 in the enalapril arm and 19 in the placebo arm). Enalapril was tolerated without hypotension or syncope when LV systolic function was preserved. Three of 5 patients with LV dysfunction and congestive heart failure had hypotension and were withdrawn. Patients who tolerated enalapril (n = 34) demonstrated significant improvement in NYHA class, Borg index (5.4 +/- 1.2 vs 5.6 +/- 1.7, P =.03), and 6-minute walk distance (402 +/- 150 vs 376 +/- 174, P =.003) compared with control subjects. Within the enalapril group, patients with associated regurgitant lesions improved the most.
ACEI are well tolerated in symptomatic patients with severe AS. Patients with congestive heart failure with LV dysfunction and low normal blood pressure are prone to have hypotension. Enalapril significantly improves effort tolerance and reduces dyspnea in symptomatic AS.
动物模型已证明血管紧张素转换酶抑制剂（ACEI）在实验性主动脉瓣狭窄（AS）中具有益处，静脉注射硝普钠已显示对伴有左心室（LV）功能障碍的AS有血流动力学改善作用。尽管ACEI在大多数心力衰竭情况下常规使用，但由于存在低血压风险，AS患者通常避免使用。我们旨在确定ACEI依那普利在有症状的严重AS患者中的临床耐受性和疗效。
有症状的严重AS患者在初始稳定后被纳入一项随机、双盲、对照试验，分为依那普利组或安慰剂组。继续使用标准抗心力衰竭药物。依那普利起始剂量为2.5mg，每日两次，逐渐增加至10mg，每日两次。主要终点是1个月时低血压的发生情况以及Borg呼吸困难指数和6分钟步行距离的改善情况。次要终点是轻度ACEI不耐受、咳嗽、先兆晕厥、纽约心脏协会分级的改善以及超声心动图参数。
共纳入56例患者（依那普利组37例，安慰剂组19例）。当左心室收缩功能保留时，依那普利耐受性良好，未出现低血压或晕厥。5例左心室功能障碍和充血性心力衰竭患者中有3例出现低血压并退出试验。与对照组相比，耐受依那普利的患者（n = 34）在纽约心脏协会分级、Borg指数（5.4±1.2对5.6±1.7，P = 0.03）和6分钟步行距离（402±150对376±174，P = 0.003）方面有显著改善。在依那普利组中，伴有反流性病变的患者改善最为明显。
ACEI在有症状的严重AS患者中耐受性良好。左心室功能障碍和血压正常偏低的充血性心力衰竭患者容易出现低血压。依那普利可显著改善有症状AS患者的运动耐力并减轻呼吸困难。
