Association of ACEI/ARB therapy with total and cardiovascular death in coronary artery disease patients with advanced chronic kidney disease: a large multi-center longitudinal study

Advanced chronic kidney disease (CKD) is common among patients with coronary artery disease (CAD), and angiotensin‑converting enzyme inhibitors (ACEI) or angiotensin‑receptor blockers (ARB) can improve cardiac and renal function, but whether ACEI/ARB therapy improves long-term prognosis remains unclear among these high-risk patients. Therefore, this research aimed to investigate the relationship between ACEI/ARB therapy and long-term prognosis among CAD patients with advanced CKD. CAD patients with advanced CKD were included in five hospitals. Advanced CKD was defined as estimated glomerular filtration rate (eGFR)&lt;30 ml/min per 1.73 m². Cox regression models and competing risk Fine and Gray models were used to examine the relationship between ACEI/ARB therapy and all-cause and cardiovascular death, respectively. Of 2527 patients, 47.6% population of our cohort was discharged on ACEI/ARB. The overall all-cause and cardiovascular mortality were 38.6% and 24.7%, respectively. Multivariate Cox regression analyses indicated that ACEI/ARB therapy was found to be associated with lower rates of both all-cause mortality (hazard ratio (HR)=0.836, 95% confidence interval (CI): 0.738–0.948, <i>p</i> = 0.005) and cardiovascular mortality (HR = 0.817, 95%CI: 0.699–0.956, <i>p</i> = 0.011). In the propensity-matched cohort, the survival benefit was consistent, and significantly better survival was observed for all-cause mortality (HR = 0.856, 95%CI: 0.752–0.974, <i>p</i> = 0.019) and cardiovascular mortality (HR = 0.830, 95%CI: 0.707–0.974, <i>p</i> = 0.023) among patients treated with ACEI/ARB. ACEI/ARB therapy showed a better survival benefit among high-risk CAD patients with advanced CKD at long-term follow-up, which manifested that strategies to maintain ACEI/ARB treatment may improve clinical outcomes among these high-risk populations. Advanced CKD is highly prevalent and strongly associated with higher mortality risk and worse outcomes among CAD patients, and patients with advanced CKD have often been excluded from randomized controlled trials, creating an evidence gap for these high-risk CAD patients. ACEI/ARB are beneficial for greater survival among CAD patients, but the effect of ACEI/ARB therapy on long-term prognosis is unclear among CAD patients with advanced CKD. ACEI/ARB treatment showed a better survival benefit among high-risk CAD patients with advanced CKD at long-term follow-up. CAD patients with advanced CKD are not only have worse outcomes but also limited in their choice of therapy strategies. Our study may prompt an important reference for the subsequent improvement of long-term prognosis among these high-risk populations.

慢性肾脏病（CKD）晚期在冠状动脉粥样硬化性心脏病（CAD）患者中十分常见。血管紧张素转换酶抑制剂（ACEI）或血管紧张素Ⅱ受体拮抗剂（ARB）可改善心脏与肾脏功能，但此类高危患者接受ACEI/ARB治疗能否改善长期预后仍不明确。因此本研究旨在探讨合并晚期CKD的CAD患者中，ACEI/ARB治疗与长期预后的关联。本研究纳入5家医院的合并晚期CKD的CAD患者。晚期CKD定义为估算肾小球滤过率（eGFR）<30 ml/min/1.73 m²。分别采用Cox回归模型与竞争风险Fine-Gray模型分析ACEI/ARB治疗与全因死亡、心血管死亡的关联。本队列共纳入2527例患者，其中47.6%的患者出院时接受ACEI/ARB治疗。整体全因死亡率与心血管死亡率分别为38.6%与24.7%。多变量Cox回归分析显示，ACEI/ARB治疗与更低的全因死亡（风险比（HR）=0.836，95%置信区间（CI）：0.738–0.948，P=0.005）及心血管死亡风险相关（HR=0.817，95%CI：0.699–0.956，P=0.011）。在倾向得分匹配队列中，生存获益趋势一致，接受ACEI/ARB治疗的患者全因死亡（HR=0.856，95%CI：0.752–0.974，P=0.019）与心血管死亡风险（HR=0.830，95%CI：0.707–0.974，P=0.023）均显著更低，生存状况更佳。长期随访结果显示，ACEI/ARB治疗可使合并晚期CKD的高危CAD患者获得更优的生存获益，提示维持ACEI/ARB治疗策略或可改善此类高危人群的临床结局。合并晚期CKD的CAD患者患病率较高，且与更高的死亡风险及更差的临床结局密切相关；而晚期CKD患者常被排除在随机对照试验之外，导致此类高危CAD患者的相关临床证据存在缺口。尽管已有研究证实ACEI/ARB可改善CAD患者的生存状况，但针对合并晚期CKD的CAD患者，ACEI/ARB治疗对其长期预后的影响仍不明确。本研究再次证实，长期随访中ACEI/ARB治疗可使合并晚期CKD的高危CAD患者获得更优生存获益。合并晚期CKD的CAD患者不仅临床结局更差，治疗策略选择也更为有限。本研究可为后续改善此类高危人群的长期预后提供重要参考依据。