Statins and kidney injury
Published in Health News and Evidence
Date published: About this date
- A recent study has suggested that the risk of acute kidney injury is higher in people using high-potency statins than in people using low-potency statins.
- This increased risk was shown in people without a history of chronic kidney disease but not in people with chronic kidney disease.
- The finding is unlikely to change clinical practice, as the risk remains small and was shown in an observational study not a randomised controlled trial.
- Further studies are needed to verify this finding and to identify which patients may be at increased risk.
- For most people prescribed a statin the benefits of reducing the risk of cardiovascular disease outweigh an increased risk of renal damage.
- Consider the potential for adverse events when choosing to treat a patient with a high-potency compared with a low-potency statin.
- Current guidelines recommend testing baseline alanine aminotransferase (ALT) and creatine kinase (CK) before starting patients on statin treatment and again when the response of lipids is assessed (1–2 months after initiation or dosage adjustment).1
- Be vigilant for changes in kidney function in patients prescribed high-potency statins, especially in the first 120 days after starting.2
- Only use high doses of statins in patients at high cardiovascular risk and those who have not achieved target lipid levels on lower doses.1,3
- Report suspected adverse reactions to the TGA online or by using the ‘Blue Card’ distributed with Australian Prescriber.
A recent Canadian study reported that use of high-potency statins was associated with higher rates of hospitalisation for acute kidney injury than use of low-potency statins.2 This generated considerable media attention.4–9
What was the study design?
This was a retrospective observational study that analysed the patient records of over 2 million statin users, most (97%) of whom did not have chronic kidney disease.2 Patient records were obtained from nine different databases; seven were from Canada, one was from the UK and one was from the US.2 Patients were aged 40 years or older and were newly treated with statins (i.e. had not been dispensed a prescription for a cholesterol-lowering drug or niacin in the previous year before the study).2
The main outcome measure was whether the risk of developing acute kidney injury was influenced by use of high-potency versus low-potency statins.2
In this study the authors categorised statins as high potency or low potency depending on whether they would produce a theoretical reduction in LDL-cholesterol of more or less than 45%*.2 This was based on a previous systematic review and meta-analysis that showed that statins are clustered around three levels of LDL-cholesterol reduction.10
High-potency statins were defined in the study as:
- ≥ 10 mg rosuvastatin
- ≥ 20 mg atorvastatin
- ≥ 40 mg simvastatin.
All other statin doses were defined as low-potency statins.2
Each patient database was analysed separately using a nested case–control design.2 Controls were matched for age, sex and time of enrolment into the study. Information from the different databases was then combined.2
*The potency of a drug usually refers to the amount of the drug that is needed to cause a specified percentage of its maximal effect, irrespective of the magnitude of the maximal effect. Statin potency, however, is usually defined by the magnitude of the drug’s effect on reducing absolute low-density lipoprotein–cholesterol (LDL-cholesterol).9
What did the study show?
People who were newly prescribed high-potency statins were 34% more likely to be hospitalised for acute kidney injury in the first 120 days after starting treatment than people who were started on low-potency statins (adjusted rate ratio 1.34, 95% confidence interval 1.25 to 1.43).2 This increased risk was shown in people without a history of chronic kidney disease, and was also seen for patients receiving this treatment for up to 2 years, although the increased risk was greatest in the first 120 days.2
This effect was not seen in patients with chronic kidney disease (adjusted rate ratio 1.10, 95% CI 0.99 to 1.23) but the study was underpowered to show a difference in this population, as very few patients with chronic kidney disease were included.2
What do the results mean?
Based on the results of this study it is estimated that 1700 patients would have to be treated with high-potency statins rather than low-potency statins for 120 days to cause one additional hospitalisation for acute kidney injury.2 These numbers only relate to patients without a history of chronic kidney disease.
Given this low incidence and the fact that patients prescribed high-potency statins are usually those considered to be at high cardiovascular risk and/or have not responded to a lower dose,1,3 the results of this study are unlikely to change clinical practice. Nevertheless, this new information provides another factor to consider in balancing the risks and benefits when deciding whether to prescribe a patient a high-potency statin as opposed to a low-potency statin.
For most people prescribed a statin, the benefits of reducing the incidence of cardiovascular events greatly outweigh the risk of acute kidney injury.
Limitations of the study
- This large trial highlights a possible link between high-potency statins and acute kidney injury in people without existing chronic kidney disease.2 However, as this was an observational study it is difficult to identify a causal relationship between high-potency statins and acute kidney injury.
- Patients were not randomised to statin dose and were prescribed a high-potency statin based on the clinical judgement of their health professional. Although the researchers adjusted the data for a large number of potential confounders (including diabetes, hypertensive disease and use of ACE inhibitors, angiotensin II-receptor blockers, thiazide and loop diuretics or prescription NSAIDs) using high dimensional propensity scores, some may not have been corrected for.
- The outcomes of the hospital admissions for acute kidney injury were not reported in the study, making it difficult to clearly determine the clinical implications of the hospitalisations.
Further information is needed to understand the differences in the safety profiles of high-potency and low-potency statins. This is likely to come from further large observational studies and postmarketing surveillance, as most randomised controlled trials are likely to be too small to identify such rare adverse events.
Health professionals can help increase this understanding of rare adverse events by reporting suspected adverse reactions to the TGA online
or by using the ‘Blue Card’ distributed three times a year with Australian Prescriber.
Further information on managing lipids, reducing cardiovascular risk see NPS News 71: Managing lipids, reducing cardiovascular risk, 2011.11
- eTG complete [online]. Therapeutic Guidelines: Cardiovascular. Melbourne: Therapeutic Guidelines Limited, 2013. http://etg.hcn.com.au/desktop/index.htm (accessed 16 May 2013).
- Dormuth CR, Hemmelgarn BR, Paterson JM, et al. Use of high-potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases. BMJ 2013;346:f880. [PubMed]
- Rossi S (ed). Australian Medicines Handbook, 2013. Adelaide: Australian Medicines Handbook Pry Ltd, 2013.
- Brill D. High-potency statins linked to kidney damage. Cardiology Update: 2013. http://www.cardiologyupdate.com.au/latest-news/high-potency-statins-linked-to-kidney-damage (accessed 16 April 2013).
- Brill D. Potent statins linked to kidney damage. Australian Doctor, 21 March 2013.
http://www.australiandoctor.com.au/news/latest-news/potent-statins-linked-to-kidney-damage (accessed 16 April 2013).
- Stiles S. "High-potency" statins linked to acute kidney injury. the heart.org, 2013. http://www.theheart.org/article/1519991.do (accessed 16 April 2013).
- Margo J. High-dose statins linked to kidney injury. Financial Review: 2013. http://www.afr.com/p/lifestyle/mens_health/high_dose_statins_linked_to_kidney_OjrMMv6EzqKtcn6E7WWBRJ (accessed 16 April 2013).
- Medline Plus. High-Dose Statins Linked to Acute Kidney Damage. 2013. http://www.nlm.nih.gov/medlineplus/news/fullstory_135078.html (accessed 16 April 2013).
- Fassett RG, Coombes JS. Statins in acute kidney injury: friend or foe? BMJ 2013;346:f1531. [PubMed]
- Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 2003;326:1423. [PubMed]
- National Prescribing Service. NPS News 71: Managing lipids, reducing cardiovascular risk. 2011. http://www.nps.org.au/publications/health-professional/nps-news/2011/lipids