Centre of Cardiovascular Research & Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Victoria, 3004, Australia.
Eur J Heart Fail. 2014 Jan;16(1):41-8. doi: 10.1002/ejhf.13. Epub 2013 Dec 11.
Impaired renal function is associated with worse clinical outcomes in patients with LV systolic dysfunction (LVSD) and heart failure. Renin-angiotensin-aldosterone system (RAAS) inhibitors provide clinical benefit in these settings and often worsen renal function. It is not clear whether worsening renal function (WRF) in patients exposed to these agents predicts a worse prognosis or merely reflects the pharmacological action of the drug on the kidney.
We performed a meta-analysis of all RAAS inhibitor LVSD trials reporting on outcomes according to WRF (as per individual study definition) in both active intervention and placebo groups. Five major studies (SOLVD, SAVE, RALES, Val-HeFT and EPHESUS) contributed, with 20 573 patients. Compared with placebo, RAAS inhibitors reduced all-cause mortality overall [n = 20 573, relative risk ratio (RR) 0.91, 95% confidence interval (CI) 0.86-0.95, P = 0.0003], in the group with no WRF (n = 18 209, RR 0.91, 95% CI 0.83-0.99, P = 0.04), and in the WRF group (n = 2364, RR 0.72, 95% CI 0.62-0.84, P < 0.0001). Compared with no WRF, WRF was associated with increased all-cause mortality; however, this was less in the RAAS inhibitor group (n = 8905, RR 1.22, 95% CI 1.10-1.36, P = 0.0003) than in the placebo group (n = 9304, RR 1.52, 95% CI 1.37-1.69, P < 0.00001).
WRF shortly after randomization is associated with worsened outcomes compared with no WRF; however, the reduction in all-cause mortality associated with the use of RAAS inhibitors was significantly greater in the presence of WRF than in the no WRF group. Clinicians should not be deterred from using RAAS inhibitors in the setting of WRF.
在左心室收缩功能障碍（LVSD）和心力衰竭患者中，肾功能受损与临床结局恶化相关。肾素-血管紧张素-醛固酮系统（RAAS）抑制剂在这些情况下提供临床益处，但常导致肾功能恶化。目前尚不清楚暴露于这些药物的患者肾功能恶化（WRF）是否预示预后更差，还是仅仅反映了药物对肾脏的药理作用。
我们对所有报告根据 WRF（根据各研究定义）的 RAAS 抑制剂 LVSD 试验进行了荟萃分析，这些试验在活性干预和安慰剂组中均有报道。五项主要研究（SOLVD、SAVE、RALES、Val-HeFT 和 EPHESUS）提供了 20573 名患者的数据。与安慰剂相比，RAAS 抑制剂总体上降低了全因死亡率[n = 20573，相对风险比（RR）0.91，95%置信区间（CI）0.86-0.95，P = 0.0003]，在无 WRF 组（n = 18209，RR 0.91，95%CI 0.83-0.99，P = 0.04）和 WRF 组（n = 2364，RR 0.72，95%CI 0.62-0.84，P < 0.0001）中降低了全因死亡率。与无 WRF 相比，WRF 与全因死亡率增加相关；然而，在 RAAS 抑制剂组（n = 8905，RR 1.22，95%CI 1.10-1.36，P = 0.0003）中，WRF 导致的全因死亡率增加幅度低于安慰剂组（n = 9304，RR 1.52，95%CI 1.37-1.69，P < 0.00001）。
与无 WRF 相比，随机分组后不久发生的 WRF 与结局恶化相关；然而，与无 WRF 组相比，RAAS 抑制剂的使用与全因死亡率的降低显著相关，而在 WRF 组中更为显著。临床医生不应因 WRF 而避免在 RAAS 抑制剂治疗中使用。
