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在一个大型的、真实世界的肝硬化患者队列中,他汀类药物、二甲双胍和肾素-血管紧张素系统(RAS)抑制剂并未降低静脉曲张出血风险和死亡率。

Statins, metformin, and RAS inhibitors did not reduce variceal bleeding risk and mortality in a large, real-life cohort of patients with cirrhosis.

作者信息

Pfisterer Nikolaus, Schwarz Michael, Schwarz Caroline, Putre Florian, Ritt Lukas, Riedl Florian, Hartl Lukas, Jachs Mathias, Mandorfer Mattias, Madl Christian, Trauner Michael, Reiberger Thomas

机构信息

Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.

Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria.

出版信息

PLoS One. 2024 Jun 13;19(6):e0302811. doi: 10.1371/journal.pone.0302811. eCollection 2024.

Abstract

BACKGROUND

Previous experimental and clinical studies suggested a beneficial effect of statins, metformin, angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers (RASi) on portal hypertension. Still, their effects on hard cirrhosis-related clinical endpoints, such as variceal bleeding and bleeding-related mortality, remain to be investigated.

METHODS

Thus, we recorded the use of statins, metformin and RASi in a large cohort of cirrhotic patients undergoing endoscopic band ligation (EBL) for primary (PP, n = 440) and secondary bleeding prophylaxis (SP, n = 480) between 01/2000 and 05/2020. Variceal (re-) bleeding and survival rates were compared between patients with vs. without these co-medications.

RESULTS

A total of 920 cirrhotic patients with varices were included. At first EBL, median MELD was 13 and 515 (56%) patients showed ascites. Statins, metformin and RASi were used by 49 (5.3%), 74 (8%), and 91 (9.9%) patients, respectively. MELD and platelet counts were similar in patients with and without the co-medications of interest. Rates of first variceal bleeding and variceal rebleeding at 2 years were 5.2% and 11.7%, respectively. Neither of the co-medications were associated with decreased first bleeding rates (log-rank tests in PP: statins p = 0.813, metformin p = 0.862, RASi p = 0.919) nor rebleeding rates (log-rank tests in SP: statin p = 0.113, metformin p = 0.348, RASi p = 0.273). Similar mortality rates were documented in patients with and without co-medications for PP (log-rank tests: statins p = 0.630, metformin p = 0.591, RASi p = 0.064) and for SP (statins p = 0.720, metformin p = 0.584, RASi p = 0.118).

CONCLUSION

In clinical practice, variceal bleeding and mortality rates of cirrhotic patients were not reduced by co-medication with statins, metformin or RASi. Nevertheless, we recommend the use of these co-medications by indication, as they may still exert beneficial effects on non-bleeding complications in patients with liver cirrhosis.

摘要

背景

既往实验和临床研究表明,他汀类药物、二甲双胍、血管紧张素转换酶抑制剂和血管紧张素II受体阻滞剂(RASi)对门静脉高压有益。然而,它们对肝硬化相关临床终点的影响,如静脉曲张出血和出血相关死亡率,仍有待研究。

方法

因此,我们记录了2000年1月至2020年5月期间,一大群接受内镜下套扎术(EBL)以预防原发性(PP,n = 440)和继发性出血(SP,n = 480)的肝硬化患者使用他汀类药物、二甲双胍和RASi的情况。比较了使用与未使用这些联合药物的患者的静脉曲张(再)出血率和生存率。

结果

共纳入920例有静脉曲张的肝硬化患者。首次EBL时,中位终末期肝病模型(MELD)评分为13分,515例(56%)患者出现腹水。分别有49例(5.3%)、74例(8%)和91例(9.9%)患者使用了他汀类药物、二甲双胍和RASi。使用与未使用相关联合药物的患者,其MELD评分和血小板计数相似。2年时首次静脉曲张出血率和静脉曲张再出血率分别为5.2%和11.7%。这些联合药物均未降低首次出血率(PP组的对数秩检验:他汀类药物p = 0.813,二甲双胍p = 0.862,RASi p = 0.919)和再出血率(SP组的对数秩检验:他汀类药物p = 0.113,二甲双胍p = 0.348,RASi p = 0.273)。PP组(对数秩检验:他汀类药物p = 0.630,二甲双胍p = 0.591,RASi p = 0.064)和SP组(他汀类药物p = 0.720,二甲双胍p = 0.584,RASi p = 0.118)中,使用与未使用联合药物的患者死亡率相似。

结论

在临床实践中,肝硬化患者联合使用他汀类药物、二甲双胍或RASi并不能降低静脉曲张出血率和死亡率。然而,我们建议根据指征使用这些联合药物,因为它们可能仍对肝硬化患者的非出血性并发症有有益作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d6/11175511/bf577322a008/pone.0302811.g001.jpg

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