Taking high-potency statins may increase the risk of acute kidney injury, according to an analysis of more than 2 million newly treated patients. Based on the results, physicians should err toward lower-dose statins, two editorial writers suggested. The study and editorial were published online March 19 in BMJ.
The JUPITER (Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin) trial found that high-dose rosuvastatin (Crestor, AstraZeneca) significantly reduced the incidence of cardiovascular events in patients, but some researchers questioned whether adverse effects might surface over extended periods of time. Subsequent data submitted to the FDA suggested that rosuvastatin might increase in the risk of acute renal failure.
To explore a dose response and possible adverse effects, Colin R. Dormuth, ScD, of the University of British Columbia in Vancouver, and colleagues in the Canadian Network for Observational Drug Effect Studies used administrative healthcare records in Canada, the U.S. and the U.K. to identify more than 2 million patients newly treated with statins between 1997 and 2008. Of the total, 59,636 had chronic kidney disease.
Their goal was to assess the association between acute kidney injury and the use of high-dose and low-dose statins. They defined high-dose statins as at least 10 mg rosuvastatin, at least 20 mg atorvastatin (Lipitor, Pfizer) and at least 40 mg simvastatin (Zocor, Merck). The primary endpoint was hospitalization after acute kidney injury.
They identified all the cases where there was hospitalization after acute kidney injury and randomly selected 10 controls from a matched risk set for their analyses. Overall, 33 percent of patients received high potency statins. Within the total group, there were 4,691 hospitalizations for acute kidney injury within 120 days of beginning statin treatment.
Those who received high-dose treatment were 34 percent more likely to be hospitalized for acute kidney injury within the first 120 days, and the risk remained higher for at least two years. The rate of hospitalization was not significantly higher in patients with chronic kidney disease, though. They calculated that compared with low-dose statins, administering high-dose statins to 1,700 patients without chronic kidney disease would result in one additional hospitalization for acute kidney injury.
“A number of 1,700 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,” Dormuth and colleagues wrote. “However, our definition of acute kidney injury was chosen to be highly specific and thus probably excluded a number of patients with real but milder cases, which could have underestimated the absolute risk.”
They suggested that the incremental cardiovascular benefit of prescribing high-dose rather than low-dose statins makes identifying which patients might be harmed with more potent doses critical.
In an accompanying editorial, Robert G. Fassett, MD, PhD, and Jeff S. Coombes, PhD, both of the University of Queensland in Brisbane, Australia, recommended that physicians prescribe low-dose statins whenever possible to balance cardiovascular benefits and renal harms. They pointed out that Dormuth et al could not pinpoint the causes and biological mechanism for acute kidney injury, and called for further research.