Aggarwal Anuradha, Wong James, Campbell Duncan J
Cardiology Department, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria, Australia.
Heart Lung Circ. 2006 Oct;15(5):306-9. doi: 10.1016/j.hlc.2006.06.003. Epub 2006 Aug 28.
Treatment of advanced systolic heart failure (HF) with the aldosterone antagonist spironolactone on the background of angiotensin converting enzyme inhibition (ACEI) is well established. However, the only large prospective trial to investigate this therapy (RALES) predated the routine use of beta-blockade in HF. The widespread practice of combining ACEI, beta-blockers and spironolactone in HF management has led to serious concerns regarding hyperkalemia. Beta-blockade has been shown to reduce circulating angiotensin (Ang) II levels in HF patients established on ACEI therapy, possibly by renin suppression.
To measure the effects of addition of the beta-blocker carvedilol to optimal ACEI therapy on aldosterone release in HF.
Seventeen patients with NYHA Class II-III HF, left ventricular ejection fraction <35%, were stabilised on diuretic and ACEI therapy. Plasma was collected for measurement of Ang II, Ang I, aldosterone and amino-terminal-pro-B-type natriuretic peptide (NT-proBNP). A 24h urine collection was obtained for measurement of aldosterone/creatinine ratio. Carvedilol was then commenced and up titrated over the next 6-8 weeks and all samples were again obtained.
Plasma Ang II levels decreased from 8.6 (0.8-94.6)fmol/mL, geometric mean (95% confidence interval) to 2.0 (0.1-61.9)fmol/mL, P=0.001, Ang I levels decreased from 96 (13-702)fmol/mL to 23 (0-1050)fmol/mL, P=0.002, and urine aldosterone/creatinine ratio decreased from 3.7 (0.9-14.8)nmol/mmol to 1.8 (0.4-8.9)nmol/mmol, P=0.01, with addition of carvedilol therapy.
It is concluded that carvedilol suppresses aldosterone production in HF patients receiving ACEI therapy. However, the clinical importance of this finding needs to be further tested from the point of view both of the likelihood of clinical benefit from aldosterone antagonists as well as the risk of hyperkalemia and whether aldosterone levels are of predictive value.
在血管紧张素转换酶抑制（ACEI）的基础上，使用醛固酮拮抗剂螺内酯治疗晚期收缩性心力衰竭（HF）已得到充分证实。然而，唯一一项研究该疗法的大型前瞻性试验（RALES）早于HF中常规使用β受体阻滞剂的时间。在HF管理中联合使用ACEI、β受体阻滞剂和螺内酯的广泛做法引发了对高钾血症的严重担忧。在接受ACEI治疗的HF患者中，β受体阻滞剂已被证明可降低循环中的血管紧张素（Ang）II水平，可能是通过抑制肾素实现的。
测量在最佳ACEI治疗基础上加用β受体阻滞剂卡维地洛对HF患者醛固酮释放的影响。
17例纽约心脏协会（NYHA）心功能II - III级的HF患者，左心室射血分数<35%，接受利尿剂和ACEI治疗使其病情稳定。采集血浆以测量Ang II、Ang I、醛固酮和氨基末端前B型利钠肽（NT - proBNP）。收集24小时尿液以测量醛固酮/肌酐比值。然后开始使用卡维地洛，并在接下来的6 - 8周内逐渐增加剂量，之后再次采集所有样本。
加用卡维地洛治疗后，血浆Ang II水平从几何平均数8.6（0.8 - 94.6）fmol/mL降至2.0（0.1 - 61.9）fmol/mL，P = 0.001；Ang I水平从96（13 - 702）fmol/mL降至23（0 - 1050）fmol/mL，P = 0.002；尿醛固酮/肌酐比值从3.7（0.9 - 14.8）nmol/mmol降至1.8（0.4 - 8.9）nmol/mmol，P = 0.01。
得出的结论是，卡维地洛可抑制接受ACEI治疗的HF患者的醛固酮生成。然而，从醛固酮拮抗剂临床获益的可能性、高钾血症风险以及醛固酮水平是否具有预测价值等角度来看，这一发现的临床重要性仍需进一步验证。
