Statins in acute kidney injury: friend or foe?BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f1531 (Published 19 March 2013) Cite this as: BMJ 2013;346:f1531
- Robert G Fassett, professor,
- Jeff S Coombes, professor
Statins have established benefits in the general population for primary and secondary prevention of cardiovascular disease. There has been a trend towards increasing the potency of statin treatment, either with larger doses—such as simvastatin or atorvastatin 40-80 mg—or with more potent forms, such as rosuvastatin. Potency is usually defined by the drug’s effect on reducing absolute low density lipoprotein-cholesterol, although the drugs’ well known pleiotropic effects are less easily quantified. Increased use of higher potency statins has partly stemmed from the outcomes of clinical trials such as the Treating to New Targets study, where high potency statins improved cardiovascular outcomes more than lower potency ones.
Because statins are now used so extensively, concerns have been expressed about their associated adverse events. In a linked paper (doi:10.1136/bmj.f880), using information from large patient databases, Dormuth and colleagues found that newly prescribed high potency statins were associated with increased risk of hospital admission for acute kidney injury compared with low potency statins at 120 days, with the risk persisting for two years. The reported side effects of statins include myopathy, liver dysfunction, cataract, and acute kidney injury, and risks of these must be considered alongside benefits. Because of the limited population size in randomised controlled trials, adverse events may not be common enough to be identified. The extent or existence of some adverse events may be evident only after postmarketing surveillance and analysis of large patient databases.
Dormuth and colleagues defined high potency statins as rosuvastatin at 10 mg or more, atorvastatin at 20 mg or more, and simvastatin at 40 mg or more, with all others deemed low potency. Their findings are supported by results from the JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial in a report by the United States Food and Drug Administration. It found a similar rate ratio estimate for acute kidney injury with the use of rosuvastatin 20 mg, a high potency statin. However, in contrast, four pharmacoepidemiological studies found no difference in incidence between those taking rosuvastatin and those on other statins.
Some studies have focused on the potential for previous administration of statins to prevent acute kidney injury in certain circumstances, such as after surgery or use of intravenous contrast agents. Statin use before major elective surgery was associated with a lower incidence of acute kidney injury, and rates were lower in users of high potency statins than in those using low potency ones. Acute kidney injury was also lower in statin users after major open abdominal, cardiac, thoracic, and vascular procedures, and high potency statins seemed to be more protective than low potency ones. However, in a retrospective study of all statin doses and a pilot randomised controlled trial of atorvastatin 40 mg, statin use before cardiac surgery was not associated with reduced incidence of acute kidney injury. High dose statin (atorvastatin 80 mg), and atorvastatin or simvastatin 40-80 mg given before intravenous contrast protected from contrast induced kidney injury, although adverse kidney outcomes such as statin induced rhabdomyolysis, which can result in acute kidney injury, are well recognised.
Risk and benefit are usually measured by the number of events per 100 000 person years, which is not easily translated in the clinical setting. The recently developed Qstatin scores, calculated from risk factors that predict statin associated adverse events, can help assess statin risk. Initially developed and validated in a large cohort, Qstatin scores have recently been independently and externally validated in a primary care population in England and Wales. On the basis of these online scores (http://qintervention.org), general practitioners can inform patients of their 10 year cardiovascular disease risk and five year acute kidney injury risk if prescribed a statin, enabling them to compare benefit with risk. However, the current score does not consider statin potency, and this new study may stimulate attempts to incorporate these data into the score. The results of the current study indicate that clinicians should use low potency statins whenever possible to provide cardiovascular benefits without the increased risk of acute kidney injury.
Despite extensive experience with the use of statins over many years, optimization of doses to derive benefit but minimise risk is still evolving. The results of the current study indicate that a randomised controlled trial is needed to compare the adverse effects of high and low potency statins. However, because rare adverse events are not always seen in trials, postmarketing surveillance and reporting from large databases will still be needed to quantify these.
The current study does not report the causes of acute kidney injury in patients admitted to hospital, and although it is most commonly attributed to rhabdomyolysis, the biological mechanism of increased risk is not yet elucidated. Further investigation of the cause of acute kidney injury requiring hospital admission should be undertaken.
Cite this as: BMJ 2013;346:f1531
Competing interests: We have read and understood the BMJ Group policy on declaration of interests and have no relevant interests to declare.
Provenance and peer review: Commissioned; not externally peer reviewed.