RAAS抑制剂联合β受体阻滞剂治疗心力衰竭的不良反应及临床应对策略

Adverse Reactions and Clinical Coping Strategies of RAAS Inhibitors Combined with β-Blockers in the Treatment of Heart Failure

摘要

目的 探讨肾素-血管紧张素-醛固酮系统（renin-angiotensin-aldosterone system, RAAS）抑制剂联合β受体阻滞剂治疗心力衰竭的不良反应发生情况及其独立危险因素，分析基于危险因素实施分层管理策略对提升临床治疗安全性与有效性的应用价值。方法 本研究采用前瞻性观察性研究设计，选取2024年2月至2025年5月延安大学咸阳医院收治的120例心力衰竭患者为研究对象，按管理策略分为规范监测组与常规管理组，各60例。经倾向性评分匹配（propensity score matching，PSM）均衡组间混杂因素后，最终纳入研究对象103例，其中规范监测组52例，常规管理组51例，所有入组患者均接受RAAS抑制剂联合β受体阻滞剂治疗。比较2组不良反应发生率、治疗中断率、6个月目标剂量达成率、N末端B型脑钠肽前体（N-terminal pro-B-type natriuretic peptide，NT-proBNP）降幅>30%比例及30 d再住院率等指标。结果 103例心力衰竭患者中，总药物相关不良反应发生率达49.51%，以低血压（28.16%）、肾功能恶化（22.33%）、心动过缓（18.45%）和高钾血症（16.50%）为主，20.39%的患者存在≥2种不良反应叠加。多因素Logistic回归分析显示，年龄>65岁以及使用高剂量RAAS抑制剂是低血压发生的独立危险因素；合并糖尿病、联用螺内酯及基线肾小球滤过率（estimated glomerular filtration rate，eGFR）<60 mL·min^-1·1.73 m^-2是高钾血症的独立危险因素；基线eGFR<60 mL·min^-1·1.73 m^-2和RAAS抑制剂高剂量是肾功能恶化的独立危险因素；而β受体阻滞剂高剂量是发生心动过缓的独立危险因素（P<0.05）。规范监测组的总不良反应发生率、治疗中断率、30 d再住院率低于常规管理组，6个月目标剂量达成率和NT-proBNP降幅>30%的比例高于常规管理组（P<0.05）。结论 RAAS抑制剂联合β受体阻滞剂治疗心力衰竭的不良反应发生率高且存在叠加效应，高龄、肾功能不全、糖尿病及高剂量用药是该联合治疗相关不良反应的独立危险因素；基于危险因素的分层管理策略可显著提升治疗安全性与有效性，改善短期预后。

Abstract

Objective To investigate the characteristics and independent risk factors of adverse drug reactions associated with combined renin-angiotensin-aldosterone system (RAAS) inhibitors and β-blockers therapy in patients with heart failure, and to evaluate the impact of a risk factor based stratified management strategy on treatment safety and efficacy. Methods A prospective observational study was conducted. A total of 120 patients with heart failure admitted to Yan’an University Xianyang Hospital from February 2024 to May 2025 were enrolled and divided into a standard monitoring group and a routine management group, with 60 cases in each group according to management strategies. After balancing confounding factors by propensity score matching (PSM), 103 patients were finally enrolled, including 52 cases in the standard monitoring group and 51 cases in the routine management group. All patients were treated with RAAS inhibitors combined with β-blockers. The two groups were compared in terms of adverse reaction incidence, treatment discontinuation rate, 6 month target dose attainment rate, proportion of patients with more than 30% reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP), and 30 day readmission rate.Results Among 103 patients with heart failure, the overall incidence of drug related adverse reactions was 49.51%, predominantly hypotension (28.16%), renal function deterioration (22.33%), bradycardia (18.45%) and hyperkalemia (16.50%). A total of 20.39% of patients experienced two or more concurrent adverse reactions. Multivariate Logistic regression analysis revealed that age over 65 years and high dose RAAS inhibitors therapy were independent risk factors for hypotension. Comorbid diabetes mellitus, combined spironolactone administration and baseline estimated glomerular filtration rate (eGFR)<60 mL·min^-1·1.73 m^-2 were independent risk factors for hyperkalemia. Baseline eGFR<60 mL·min^-1·1.73 m^-2 and high dose RAAS inhibitors were independent risk factors for renal function deterioration, and high dose β-blockers was an independent risk factor for bradycardia (P<0.05). Compared with the routine management group, the standardized monitoring group had lower total adverse reaction incidence, treatment discontinuation rate and 30 day readmission rate, and higher 6 month target dose attainment rate and proportion of patients with NT-proBNP reduction exceeding 30% (P<0.05).Conclusion Combination therapy with RAAS inhibitors and β-blockers in heart failure is associated with a high incidence of adverse reactions, which frequently co-occur. Advanced age, renal impairment, diabetes mellitus, and high dose drug regimens are independent risk factors for adverse reactions related to this combination therapy; a risk factor-guided stratified management strategy significantly enhances both the safety and effectiveness of therapy and improves short term clinical outcomes.

关键词

肾素-血管紧张素-醛固酮系统抑制剂 / β受体阻滞剂 / 心力衰竭 / 药物相关不良反应 / 危险因素分层管理

Key words

renin-angiotensin-aldosterone system inhibitor / β-blocker / heart failure / drug-related adverse reaction / risk factor-based stratified management

参考文献

[1] 王少民, 邓娣, 付慧. 达格列净联合沙库巴曲缬沙坦治疗老年心力衰竭患者疗效及对血清NT—proBNP、hs—TnT水平的影响[J].老年医学与保健, 2025, 31(1):125-130.

[2] 张虎, 刘艳梅, 杨振. 沙库巴曲缬沙坦钠在缺血性心肌病心力衰竭治疗中的应用效果及安全性[J].山东医药, 2024, 64(22):76-78.

[3] 庞翀, 陈群娟. 缬沙坦联合富马酸比索洛尔对老年高血压心脏病患者相关生化指标、炎症因子及氧化应激水平的影响[J].中国老年学杂志, 2021, 41(4):673-676.

[4] 王美力, 蔡海滨, 李东升. 培哚普利联合卡维地洛对老年充血性心力衰竭患者心功能及炎性指标的影响[J].岭南心血管病杂志, 2021, 27(1):67-71.

[5] Skouri H, Girerd N,et al. Clinical management and therapeutic optimization of patients with heart failure with reduced ejection fraction and low blood pressure. a clinical consensus statement of the heart failure association (HFA) of the ESC[J].Eur J Heart Fail, 2025, 27(4):707-722.

[6] 中华医学会心血管病学分会, 中国医师协会心血管内科医师分会, 中国医师协会心力衰竭专业委员会, 等. 中国心力衰竭诊断和治疗指南2024[J].中华心血管病杂志, 2024, 52(3):235-275.

[7] Leon S J, Whitlock R, Rigatto C,et al. Hyperkalemia—related discontinuation of renin—angiotensin—aldosterone system inhibitors and clinical outcomes in CKD: a population—based cohort study[J].Am J Kidney Dis, 2022, 80(2):164-173.e1.

[8] Mahmud H A, Palmer B F . Management of hyperkalemia in renin—angiotensin—aldosterone system inhibitor: strategies to maintain chronic kidney disease patients with type II diabetes on therapy[J].Cardiorenal Med, 2024:191-201.

[9] 李永斌, 任颖, 程立松, 等. 伊伐布雷定对急性心肌梗死使用β受体阻滞剂后心率控制不佳患者的疗效观察: 一项实用性随机对照试验研究[J].中国心血管杂志, 2025, 30(3):278-283.

[10] 骈溶亮, 刘朝阳, 仝国栋, 等. 高钾血症和肾素—血管紧张素—醛固酮系统抑制剂治疗与急性心力衰竭合并肾功能不全患者预后的相关性分析[J].中国合理用药探索, 2022, 19(12):44-50.

[11] 吴燕, 梁少丽. 培哚普利联合富马酸比索洛尔对心衰患者心功能、日常生活能力和生活质量的影响[J].心血管康复医学杂志, 2021, 30(4):419-423.

[12] Weir M R, Rossignol P, Pitt B,et al. Patiromer—facilitated renin—angiotensin—aldosterone system inhibitor utilization in patients with heart failure with or without comorbid chronic kidney disease: subgroup analysis of DIAMOND randomized trial[J].Am J Nephrol, 2024:1-18.

[13] 苗依婷, 葛亚龙, 黄晶, 等. 沙库巴曲缬沙坦治疗老年顽固性心力衰竭疗效优势的Meta分析[J].药学研究, 2024, 43(4):402-408.

[14] 唐尚仪, 张晓静, 郭宝剑, 等. 防治心力衰竭新药临床应用及研究进展[J].河北医药, 2023, 45(13):2041-2045.

[15] 马洋, 吴殿秀, 魏大军. 沙库巴曲缬沙坦钠片联合芪苈强心胶囊治疗射血分数中间值心力衰竭的效果观察[J].北华大学学报(自然科学版), 2023, 24(5):602-606.

[16] Strauss M H, Hall A S, Narkiewicz K . The combination of beta—blockers and ACE inhibitors across the spectrum of cardiovascular diseases[J].Cardiovasc Drugs Ther, 2023, 37(4):757-770.