'High-Potency' Statins Linked to Acute Kidney Injury in Analysis

March 20, 2013

MONTREAL — Taking statins at "high-potency" dosages, with levels depending on the agent, appears to raise the adjusted risk of acute kidney injury by 34% over the first four months of treatment, compared with taking lower-dose statins, suggests an analysis[1].

In the study, from Dr Colin R Dormuth (University of British Columbia, Vancouver) and colleagues and based on data from observational cohorts predominantly in Canada but also the UK and US, the high-potency statins were rosuvastatin (Crestor, AstraZeneca) at >10 mg/day, atorvastatin at >20 mg/day, and simvastatin at >40 mg/day. Statins at other dosages were defined as "low-potency."

The findings were published online today in BMJ.

A key message from the study is that, for patients prescribed statins for the first time, "if a decision is to be made about whether to start at high vs low potency, one needs to consider this additional risk that's most prominent in the first 120 days after starting," coauthor J Michael Paterson (Institute for Clinical Evaluative Sciences, Toronto, ON) told heartwire .

The absolute risk of acute kidney injury on statins is low, "in the range of one to three or four per thousand over six months," he said. "But there is this incremental difference related to whether you start on a high- vs a low-potency statin. And it could be an important difference, particularly among patients who are at very low risk of cardiovascular disease." So, "among primary-prevention patients with very few risk factors, this sort of information could be quite useful in decision making," he said. In secondary prevention, "while it’s a decision that patients and physicians have to make together, they may be willing to waive the incremental risk, the 34% increase, if the risk of cardiovascular events is very high." But all of that is speculation, Paterson emphasized.

From a total of 2 067 639 patients aged >40 years who started on statin therapy for the first time from 1997 to 2008, including almost 60 000 patients with a history of chronic kidney disease (CKD), each patient hospitalized with acute kidney injury over the next 120 days was propensity-matched to 10 who didn't develop acute kidney injury.

The rate ratio (RR) for hospitalization for acute kidney injury for users of high-potency vs low-potency statins was 1.34 (95% CI 1.25–1.43) for those without a CKD history and a nonsignificant 1.10 (95% CI 0.99–1.23) for those with a history of CKD. According to Paterson, there were comparatively few patients with a CKD history, so the finding for them is underpowered and probably not clinically relevant.

"We estimate that 1700 patients [without CKD] need to be treated with a high-potency statin instead of a low-potency statin for 120 days to cause one additional hospitalization for acute kidney injury," the group writes. That number of patients "is sufficiently large for there not to be enough patients enrolled in randomized trials to find an association between acute kidney injury and statin use with high precision."

An accompanying editorial from Drs Robert G Fassett and Jeff S Coombes (University of Queensland, Brisbane, Australia) notes that there exists a scoring system for allowing patients to compare potential benefits of statins vs associated risk of acute kidney injury[2]. "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."

In the analysis from Dormuth et al, the dividing line between statin high-potency and low potency derived from whether or not the statin dosage would lead to <45% reduction in low-density-lipoprotein (LDL) cholesterol levels.

In this "inaugural study" of the Canadian Network for Observational Drug Effect Studies (CNODES)--which is funded by grants fromHealth Canada, the Canadian Drug Safety and Effectiveness Network, and the Canadian Institutes of Health Research--Dormuth had no disclosures; disclosures for the coauthors are listed in the paper. Neither Fassett nor Coombes had disclosures.