HMG CoA reductase inhibitors (statins) for dialysis patients

  • Conclusions changed
  • Review
  • Intervention

Authors

  • Suetonia C Palmer,

    1. University of Otago Christchurch, Department of Medicine, Christchurch, New Zealand
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  • Sankar D Navaneethan,

    1. Glickman Urological and Kidney Institute, Cleveland Clinic, Department of Nephrology and Hypertension, Cleveland, OH, USA
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  • Jonathan C Craig,

    1. The University of Sydney, Sydney School of Public Health, Sydney, NSW, Australia
    2. The Children's Hospital at Westmead, Cochrane Renal Group, Centre for Kidney Research, Westmead, NSW, Australia
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  • David W Johnson,

    1. Princess Alexandra Hospital, Department of Nephrology, Woolloongabba, Queensland, Australia
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  • Vlado Perkovic,

    1. The George Institute for Global Health, Renal and Metabolic Division, Camperdown, NSW, Australia
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  • Sagar U Nigwekar,

    1. Harvard Medical School, Brigham and Women's Hospital, Massachusetts General Hospital, Scholars in Clinical Sciences Program, Boston, MA, USA
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  • Jorgen Hegbrant,

    1. Diaverum Renal Services Group, Medical Office, Lund, Sweden
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  • Giovanni FM Strippoli

    Corresponding author
    1. The University of Sydney, Sydney School of Public Health, Sydney, NSW, Australia
    2. The Children's Hospital at Westmead, Cochrane Renal Group, Centre for Kidney Research, Westmead, NSW, Australia
    3. University of Bari, Department of Emergency and Organ Transplantation, Bari, Italy
    4. Mario Negri Sud Consortium, Department of Clinical Pharmacology and Epidemiology, Santa Maria Imbaro, Italy
    5. Diaverum, Medical-Scientific Office, Lund, Sweden
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Abstract

Background

People with advanced kidney disease treated with dialysis experience mortality rates from cardiovascular disease that are substantially higher than for the general population. Studies that have assessed the benefits of statins (HMG CoA reductase inhibitors) report conflicting conclusions for people on dialysis and existing meta-analyses have not had sufficient power to determine whether the effects of statins vary with severity of kidney disease. Recently, additional data for the effects of statins in dialysis patients have become available. This is an update of a review first published in 2004 and last updated in 2009.

Objectives

To assess the benefits and harms of statin use in adults who require dialysis (haemodialysis or peritoneal dialysis).

Search methods

We searched the Cochrane Renal Group's Specialised Register to 29 February 2012 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.

Selection criteria

Randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of statins with placebo, no treatment, standard care or other statins on mortality, cardiovascular events and treatment-related toxicity in adults treated with dialysis were sought for inclusion.

Data collection and analysis

Two or more authors independently extracted data and assessed study risk of bias. Treatment effects were summarised using a random-effects model and subgroup analyses were conducted to explore sources of heterogeneity. Treatment effects were expressed as mean difference (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI).

Main results

The risk of bias was high in many of the included studies. Random sequence generation and allocation concealment was reported in three (12%) and four studies (16%), respectively. Participants and personnel were blinded in 13 studies (52%), and outcome assessors were blinded in five studies (20%). Complete outcome reporting occurred in nine studies (36%). Adverse events were only reported in nine studies (36%); 11 studies (44%) reported industry funding.

We included 25 studies (8289 participants) in this latest update; 23 studies (24 comparisons, 8166 participants) compared statins with placebo or no treatment, and two studies (123 participants) compared statins directly with one or more other statins. Statins had little or no effect on major cardiovascular events (4 studies, 7084 participants: RR 0.95, 95% CI 0.88 to 1.03), all-cause mortality (13 studies, 4705 participants: RR 0.96, 95% CI 0.90 to 1.02), cardiovascular mortality (13 studies, 4627 participants: RR 0.94, 95% CI 0.84 to 1.06) and myocardial infarction (3 studies, 4047 participants: RR 0.87, 95% CI 0.71 to 1.07); and uncertain effects on stroke (2 studies, 4018 participants: RR 1.29, 95% CI 0.96 to 1.72).

Risks of adverse events from statin therapy were uncertain; these included effects on elevated creatine kinase (5 studies, 3067 participants: RR 1.25, 95% CI 0.55 to 2.83) or liver function enzymes (4 studies, 3044 participants; RR 1.09, 95% CI 0.41 to 1.25), withdrawal due to adverse events (9 studies, 1832 participants: RR 1.04, 95% CI 0.87 to 1.25) or cancer (2 studies, 4012 participants: RR 0.90, 95% CI 0.72 to 1.11). Statins reduced total serum cholesterol (14 studies, 1803 participants; MD -44.86 mg/dL, 95% CI -55.19 to -34.53) and low-density lipoprotein cholesterol (12 studies, 1747 participants: MD -39.99 mg/dL, 95% CI -52.46 to -27.52) levels. Data comparing statin therapy directly with another statin were sparse.

Authors' conclusions

Statins have little or no beneficial effects on mortality or cardiovascular events and uncertain adverse effects in adults treated with dialysis despite clinically relevant reductions in serum cholesterol levels.

摘要

羥甲基戊二醯輔酶A(HMG CoA)還原酶抑制劑(statins)用於透析病人

背景

需接受透析治療的嚴重腎臟病病人心血管疾病死亡率高於一般人。研究指出statins (HMG CoA還原酶抑制劑)對透析病人的好處仍有爭議,統合分析也未證實statins對不同程度腎臟病是否有好處。近來有關statins用於透析病人的結果數據已經發表。本篇回顧第一次發表是在2004年,最近一次更新是在2009年。

目的

評估statins用於成人血液或腹膜透析治療之效益和風險。

搜尋策略

我們透過搜尋與本篇回顧相關的字彙與研究試驗專員連繫,搜尋考科藍腎臟群組專業註冊 (Cochrane Renal Group's Specialised Register) (截至2012年2月29日為止)。

選擇標準

我們納入隨機對照試驗和類隨機對照試驗,比較介入組(statins)和對照組(安慰劑或未接受治療或標準治療或其他statins)對成人透析治療之死亡率、心血管事件、治療相關毒性。

資料收集與分析

兩位(含)以上作者獨立擷取數據並評估研究風險偏差。以隨機效應模組分析治療作用,執行次群組分析評估異質性來源。連續性變項終點以平均值差呈現,二分變項終點以風險比和95%信賴區間呈現。

主要結果

所納入之研究多數屬高風險性偏差。隨機順序產生偏差有3篇(占12%),分派隱匿偏差有4篇(占16%)。有13篇(占52%)研究對受試者和研究人員採行盲法,有5篇研究(占20%)對受試者和研究人員及資料分析人員採行盲法。有9篇研究(占36%)有完整報告資料。有9篇研究(占36%)有報導不良事件。有11篇研究(占44%)由業界資助。

本篇回顧我們共納入25篇研究(8289位受試者),有23篇研究(8166位受試者)是比較statin和安慰劑或未接受治療之間的作用,有2篇研究(123位受試者)是直接比較不同statins之間的作用。有4篇研究(7084位受試者)結果顯示statins對降低主要心血管事件未達統計顯著差異(RR 0.95, 95% CI 0.88 to 1.03),有13篇研究(4705位受試者)結果顯示statins對降低全因死亡率未達統計顯著差異(RR 0.96, 95% CI 0.90 to 1.02),有13篇研究(4627位受試者)結果顯示statins對降低心血管死亡率未達統計顯著差異(RR 0.94, 95% CI 0.84 to 1.06),有3篇研究(4047位受試者)結果顯示statins對降低心肌梗塞事件未達統計顯著差異(RR 0.87, 95% CI 0.71 to 1.07),有2篇研究(4018位受試者)結果顯示statins對降低中風事件未達統計顯著差異(RR 1.29, 95% CI 0.96 to 1.72)。

接受statin治療發生不良事件之風險未知,這些不良事件包括如下:有5篇研究(3067位受試者)結果顯示肌酸激酶上升( RR 1.25, 95% CI 0.55 to 2.83),有4篇研究(3044位受試者)結果顯示肝功能酵素上升(RR 1.09, 95% CI 0.41 to 1.25),有9篇研究(1832位受試者)結果顯示因不良事件而退出試驗(RR 1.04, 95% CI 0.87 to 1.25),有2篇研究(4012位受試者)結果顯示罹癌(RR 0.90, 95% CI 0.72 to 1.11)。有14篇研究(1803位受試者)結果顯示statins可以降低血中總膽固醇濃度(MD -44.86 mg/dL, 95% CI -55.19 to -34.53),有12篇研究(1747位受試者)結果顯示statins可以降低低密度脂蛋白膽固醇濃度(MD -39.99 mg/dL, 95% CI -52.46 to -27.52)。不同statins之間直接比較的數據稀疏。

作者結論

雖然statins可以降低血中膽固醇濃度,但是statins對接受透析治療之成人的死亡率或心血管事件只有些許作用甚或沒有作用,而且具有不確定性的不良事件。

譯註

翻譯者:江吉文(Chi-Wen Chiang)
服務單位:屏東醫院,藥劑科(Department of Pharmacy, Pingtung Hospital, MOHW)
職稱:藥師;RPh, CDE, PhD, Assistant Professor

本翻譯計畫由臺北醫學大學考科藍臺灣研究中心(Cochrane Taiwan)、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行
聯絡E-mail:cochranetaiwan@tmu.edu.tw

Plain language summary

Does statin therapy improve survival or reduce risk of heart disease in people on dialysis?

Adults with severe kidney disease who are treated with dialysis have high risks of developing heart disease. Statin treatment reduces risks of death and complications of heart disease in the general population.

In 2009 we identified 14 studies, enrolling 2086 patients, and found that while statins were generally safe and reduced cholesterol levels, they did not prevent death or clinical cardiac events in people treated with dialysis. This latest update analysed a total or 25 studies (8289 patients), and included the results from two new large studies. We found that statins lowered cholesterol in people treated with dialysis but did not prevent death, heart attack, or stroke.

Evidence for side-effects was incomplete, and potential harms from statin therapy remain uncertain. Current study data did not address whether statin treatment should be stopped when a person starts dialysis, although the benefits associated with continued treatment are likely to be small. Limited information was available for people treated with peritoneal dialysis, suggesting that more research is needed in this setting.

淺顯易懂的口語結論

透析病人接受statin治療是否可以改善存活率或降低心臟病風險?

需接受透析治療之嚴重腎病成人發生心臟病的風險較高。一般人接受statin治療可以降低死亡風險和心臟病併發症。

2009年我們納入14篇研究共2086位受試者,研究發現透析病人接受statin治療是安全的而且可以降低膽固醇濃度,但是無法預防死亡或心臟事件。本次最新回顧我們共納入25篇研究(8289位受試者),且納入2篇新的大型研究結果。我們發現statins可以降低透析病人膽固醇濃度,但是無法預防死亡、心臟病或中風。

Statins治療副作用證據不全,且潛在性傷害不確定。雖然規律服用statin有一些好處,但是目前研究數據無法告訴透析病人是否應該停用statin。接受腹膜透析病人相關訊息有限,建議未來在這方面應該要有更多的研究。

譯註

翻譯者:江吉文(Chi-Wen Chiang)
服務單位:屏東醫院,藥劑科(Department of Pharmacy, Pingtung Hospital, MOHW)
職稱:藥師;RPh, CDE, PhD, Assistant Professor

本翻譯計畫由臺北醫學大學考科藍臺灣研究中心(Cochrane Taiwan)、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行
聯絡E-mail:cochranetaiwan@tmu.edu.tw

Laienverständliche Zusammenfassung

Verbessert die Statin-Therapie das Überleben oder vermindert sie das Risiko von Herzkrankheiten bei Menschen an der Dialyse?

Erwachsene mit schweren Nierenerkrankungen, die mit Dialyse behandelt werden, haben ein hohes Risiko für Herzkrankheiten. Statin-Behandlung reduziert das Sterberisiko und die Komplikationen von Herzkrankheiten in der allgemeinen Bevölkerung.

Im Jahr 2009 identifizierten wir 14 Studien, die 2086 Patienten einschlossen, und stellten fest, dass während Statine im Allgemeinen verträglich waren und den Cholesterinspiegel senkten, sie nicht Tod oder klinische Vorfälle die das Herz betreffen bei Patienten, die an der Dialyse sind, verhindern. Diese neueste Aktualisierung analysiert die Gesamtzahl von 25 Studien (8289 Patienten) und enthält die Ergebnisse von zwei neuen großen Studien. Wir haben festgestellt, dass Statine das Cholesterin bei Patienten, die mit Dialyse behandelt werden senken, aber nicht Tod, Herzinfarkt oder Schlaganfall verhindern.

Die Evidenz für Nebenwirkungen war unvollständig, und mögliche Schäden von der Statin-Therapie bleiben ungewiss. Aktuelle Studiendaten befassten sich nicht damit, ob die Statin-Behandlung beendet werden sollte, wenn eine Person mit der Dialyse beginnt, obwohl die Vorteile, die mit einer kontinuierlichen Behandlung verbunden sind, wahrscheinlich gering sind. Über Menschen, die mit Peritonealdialyse behandelt wurden, waren nur eingeschränkte Informationen vorhanden, was darauf hindeutet, dass mehr Forschung in diesem Setting gebraucht wird.

Anmerkungen zur Übersetzung

K. Kunzweiler, Koordination durch Cochrane Schweiz.

Резюме на простом языке

Улучшает ли терапия статинами выживание или уменьшает ли риск сердечно-сосудистых заболеваний у людей, находящихся на диализе?

Взрослые с тяжелой формой заболевания почек, которые лечатся диализом, имеют высокий риск развития сердечно-сосудистых заболеваний. Лечение статинами снижает риск смерти и осложнений сердечно-сосудистых заболеваний в общей популяции.

В 2009 году мы определили 14 исследований, включивших в общей сложности 2086 пациентов, и обнаружили, что, в то время как статины были в целом безопасны и снижали уровни холестерина, они не предотвращали смерти или клинические сердечные события у людей, находящихся на диализе. В этом последнем обновлении обзора мы проанализировали в общей сложности 25 исследований (8289 пациентов), и включали результаты двух новых крупных исследований. Мы обнаружили, что статины снизили уровень холестерина у людей, получавших диализ, но не уменьшили частоту смертей, сердечных приступов или инсультов.

Доказательства побочных эффектов были неполными, и потенциальный вред от терапии статинами остаётся неопределенным. Во включенных исследованиях не обращались к вопросу, следует ли остановить лечение статинами, когда человек начинает получать диализ, хотя польза, связанная с продолжением лечения, вероятно, будет мала. В отношении людей, получавших перитонеальный диализ, была доступна только ограниченная информация, что позволяет предполагать, что необходимы дальнейшие исследования в этой области.

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