降血壓藥物對透析患者全死因死亡及心血管事件之影響：系統性回顧及網絡統合分析

Abstract

研究目的: 比較各種降血壓藥物對於透析患者全死因死亡與心血管事件的影響。 研究設計: 對於隨機分派試驗及觀察性研究，進行系統性文獻回顧，並使用頻率學派架構之網絡統合分析。 資料來源: 本研究針對2018年9月30日以前，於PubMed、Web of Science及Cochrane Library三個電子資料庫中已發表之文獻進行搜尋。 文獻選擇: 選擇文獻之標準：研究對象需為18歲以上之成年透析患者；使用各類降血壓藥物作為介入治療，降血壓藥物包含但不限於如乙型阻斷劑、鈣離子阻斷劑、血管張力素轉化酶抑制劑、血管張力素受體阻斷劑及礦物性皮質素受體阻斷劑等；最長追蹤期間為6個月以上，且有報告至少下列一種的結果事件：全死因死亡、心血管死亡及心血管事件；研究類型為隨機分派試驗及觀察性研究。 資料收集: 本研究萃取各個文獻之患者特徵及重要資訊，包括發生結果事件之人數。針對各個成對治療比較之統合結果測量則以勝算比(odds ratio, OR)及95%信賴區間(95% confidence interval, 95% CI)來表示。 研究結果: 本研究總共收錄了19篇隨機分派試驗及5篇觀察性研究、包含59327位受試者、7704件全死因死亡、3745件心血管死亡及4746件心血管事件。與安慰劑相比，礦物性皮質素受體阻斷劑(OR=0.48, 95% CI 0.23-1.00)及血管張力素受體阻斷劑(OR=0.61, 0.39-0.95)顯著地降低全死因死亡的風險，且礦物性皮質素受體阻斷劑被排序為最有效的藥物。儘管礦物性皮質素受體阻斷劑及血管張力素受體阻斷劑同時可以顯著地降低心血管死亡之風險，乙型阻斷劑(OR=0.23, 0.11-0.48)則比這兩種藥物對於心血管死亡更具有保護效果。本研究亦發現同時合併使用血管張力素轉化酶抑制劑與血管張力素受體阻斷劑會增加全死因死亡(OR= 2.73, 1.29-5.75)及心血管死亡(OR= 3.46, 1.83-6.59)的風險，而此一結果主要來自於觀察性研究。 結論: 透過網絡統合分析，本研究發現礦物性皮質素受體阻斷劑及血管張力素受體阻斷劑可以降低全死因死亡以及心血管死亡的風險，而乙型阻斷劑則是對於預防心血管死亡最有效的藥物。此外，同時合併使用血管張力素轉化酶抑制劑與血管張力素受體阻斷劑對患者可能會有不良的影響。

Objective To assess the effects of different classes of antihypertensive agents on all-cause mortality and cardiovascular outcome in patients under dialysis. Design Systematic review and network meta-analysis of randomized controlled trials and observational studies within frequentist framework. Data sources Electronic literature search of PubMed, Web of Science and Cochrane library for published studies up to September 30, 2018. Study selection Randomized controlled trials (RCTs) and observational studies of anti-hypertension treatments, including but not limited to angiotensin receptor blocker (ARB), calcium channel blocker (CCB), mineralocorticoid receptor antagonist (MRA), in adult dialysis patients with a follow-up of at least 6 months, reporting all-cause mortality, cardiovascular (CV) mortality and CV events. Data extraction Information and patients’ characteristics of each study were extracted, including number of events for each outcome. Pooled estimates were presented as odds ratios (OR) and 95% confidence interval (CI) for dichotomous outcomes of each comparisons between two treatments.

Results Total 19 RCTs and 5 observational studies with 59327 participants were identified, including 7704 all-cause mortality, 3745 CV mortality and 4746 CV events. MRA and ARB significantly reduced the risk of all-cause mortality compared to placebo (OR for MRA= 0.48, 95% CI 0.23-1.00; OR for ARB=0.61, 0.39-0.95). MRA was ranked first according to the highest value of estimated surface under the cumulative ranking curve. Contrast to MRA and ARB, β-blocker was most protective (OR= 0.23, 0.11-0.48) and ranked best in terms of CV mortality. We also found dual therapy (ACEI+ARB) harmful and ranked the worst treatment choice for each outcome (OR for all-cause mortality= 2.73, 1.29-5.75; OR for CV mortality= 3.46, 1.83-6.59), but most evidence was obtained from observational studies. Conclusion By applying NMA, MRA and ARB significantly reduced the risks of CV and all-cause mortality compared to placebo in dialysis patients. Contrast to MRA, which was ranked first to prevent all-cause mortality, β-blocker was more protective and ranked higher in terms of CV mortality. We also showed the harmful effects of ACEI+ARB on each outcome.