- 學位論文
初探貧血與 sacubitril/valsartan 治療對心衰竭病人預後之影響
A Pilot Study Investigating the Effects of Anemia and Sacubitril/Valsartan Therapy on the Outcome of Heart Failure with Reduced Ejection Fraction Patients
摘要
研究背景 貧血為心衰竭的共病症之一，會降低心衰竭病人之灌流液 (perfusate) 品質、運動耐受性 (exercise capacity) 並增加住院率或死亡率。貧血主因之一為鐵質缺乏，因此國際心衰竭治療指引建議每年必須追蹤一次鐵質概況 (iron profile)，並根據血紅素測量值給予鐵劑治療。此外，慢性腎臟疾病或使用腎素－血管收縮素－醛固酮系統 (renin-angiotensin-aldosterone system, RAAS) 阻斷劑等亦為貧血可能原因，而目前最新 RAAS 阻斷藥物 sacubitril/valsartan 療效是否與病人的貧血狀況相互影響尚無佐證。本研究先探討臺大醫院心衰竭病人貧血的追蹤狀況，再初步分析貧血與sacubitril/valsartan 治療對心衰竭病人預後之影響。 研究方法與結果 首先，本研究回溯性分析 2017 年 1 月 1 日至 2019 年 12 月 31 日之臺大醫院心衰竭病人檢驗數據，於699 位心衰竭病人中，貧血盛行率為 54.1%，每年規律追蹤血紅素和鐵質概況的比率分別為 61.8% 和 7.2%。接著，回溯 2020 年 4 月 1 日前啟用 sacubitril/valsartan 的心衰竭病人之檢驗數據、共病症與併用藥，以死亡或心臟移植事件進行單變項分析和存活分析。於 236 位接受 sacubitril/valsartan 治療之心衰竭病人中，貧血盛行率 51.3%。與死亡或心臟移植事件顯著相關之變項包含病人用藥前之 NT-proBNP (存活 4804 ± 6899 pg/mL vs. 事件 6395 ± 7289 pg/mL，p = 0.0454) 、左心室射出分率 (left ventricular ejection fraction, LVEF) (存活 30.60 ± 7.15% vs. 事件 25.72 ± 7.20%，p = 0.0020) 及血液尿素氮 (blood urea nitrogen, BUN) (存活 25.6 ± 14.2 mg/dL vs. 事件 32.5 ± 21.8 mg/dL，p = 0.0489)。此外，用藥後 12 個月血紅素低於12 g/dL 者，死亡或心臟移植事件發生率顯著增加 (風險比值 3.714，95% 信賴區間 = 1.205 – 11.44，p = 0.0037)。 結論 本研究顯示臺大醫院心衰竭病人的貧血和鐵質追蹤狀況尚不符合國際治療指引建議，而影響 sacubitril/valsartan 治療成效的變項包含 NT-proBNP、LVEF、BUN 和血紅素。未來建議延長觀察期限並擴大病人數目，利用多變項迴歸分析，釐清貧血影響 sacubitril/valsartan 治療成效之關係。
並列摘要
Background Anemia, one of the common comorbidities of heart failure, will decrease perfusate quality and exercise capacity as well as increase hospitalization and mortality. Iron deficiency is one of its major causes. Therefore, international guidelines have recommended that iron profiles be evaluated annually. Iron deficiency should be treated with intravenous iron, with the dose calculated according to the hemoglobin levels. Furthermore, using renin-angiotensin-aldosterone system (RAAS) blockers can also cause anemia. The mutual effects of the newest RAAS blocker, sacubitril/valsartan, and anemia on heart failure patients are currently unknown. The aim of this study is to audit whether iron profiles are adequately evaluated at NTUH, as well as investigate the effects of anemia and sacubitril/valsartan therapy on heart failure patients. Methods and Results First, we retrospectively analyzed the laboratory data of heart failure patients at NTUH from January 1, 2017 to December 31 2019. Prevalence of anemia was 54.1% in 699 patients. Regular hemoglobin and iron profile evaluations accounted for 61.8% and 7.2%, respectively. Next, we retrospectively analyzed the laboratory data, comorbidities and concurrent medications of patients who initiated sacubitril/valsartan before April 1, 2020. Univariate analysis and survival analysis were performed with death or heart transplant as the composite outcome. Anemia prevalence was 51.3% in 236 patients. Factors associated with patient outcome included baseline NT-proBNP (survivors 4804 ± 6899 pg/mL vs. event 6395 ± 7289 pg/mL, p = 0.0454), LVEF (survivors 30.60 ± 7.15% vs. event 25.72 ± 7.20%, p = 0.0020), and BUN (survivors 25.6 ± 14.2 mg/dL vs. event 32.5 ± 21.8 mg/dL, p = 0.0489). Hemoglobin level below 12 mg/dL at 12 months after therapy initiation also significantly increased risk of death or heart transplant (hazard ratio 3.714, 95% confidence interval 1.205 – 11.44, p = 0.0037) Conclusion This study showed that anemia and iron deficiency follow-ups were not adequately performed at NTUH. Factors affecting sacubitril/valsartan therapy outcomes included NT-proBNP, LVEF, BUN and hemoglobin levels. Future studies are recommended to increase patient numbers and lengthen observation period. The effect of anemia on sacubitril/valsartan therapy should be assessed with multivariate regression analysis.