March 20th, 2013

High Potency Statins Linked to Increased Risk for Acute Kidney Injury

Although the beneficial effects of high-potency statins have been well-characterized in clinical trials, these same trials have lacked the power to illuminate rare but potentially important adverse events. A suggestion of one such area of concern, acute kidney injury, was first raised in the SATURN trial. Now, a new study published in BMJ provides further information about this area.

Researchers in the Canadian Network for Observational Drug Effect Studies (CNODES) performed a retrospective observational analysis of administrative databases in Canada, the U.K., and the U.S. containing more than 2 million patients newly treated with statins.  Of these, 59,636 of the subjects already had chronic kidney disease. One-third of the subjects received high potency statins, defined as ≥10 mg rosuvastatin, ≥20 mg atorvastatin, and ≥40 mg simvastatin.

Within 120 days of starting treatment there were 4691 hospitalizations for acute kidney injury in patients without pre-existing kidney disease and 1896 hospitalizations in patients with pre-existing disease. Patients without pre-existing disease on high potency statins were 34% more likely to be hospitalized with acute kidney injury than patients on other statin regimens. Patients with pre-existing disease did not have a significant increase in risk if they were taking high potency statins.

The authors estimated that 1,700 patients without pre-existing kidney disease would need to be treated with a high potency statin instead of a low potency statin to cause one additional acute kidney injury requiring hospitalization. The findings, according to the authors, are broadly consistent with the JUPITER trial. They write:

Given what is likely to be a small magnitude of incremental cardiovascular benefit of high potency statins over low potency statins in reality, a pressing question is how to identify patients for whom the risk-benefit balance for high potency statin treatment is unfavourable.

In an accompanying editorial, Robert Fassett and Jeff Coombes write that “clinicians should use low potency statins whenever possible to provide cardiovascular benefits without the increased risk of acute kidney injury.” Further, they note, “despite extensive experience with the use of statins over many years, optimization of doses to derive benefit but minimize risk is still evolving.”



One Response to “High Potency Statins Linked to Increased Risk for Acute Kidney Injury”

  1. Rafael Diaz, MD says:

    Observational studies lead to dissimilar (maybe misleading) interpretations.

    Clinical trial data:

    In the TNT trial (intensive vs. less intensive atorvastatin) there were 5 cases of rhabdomyolysis, 3 in the 10mg and 2 in the 80mg atorvastatin group (in one patient in the 80 mg group, acute renal failure was reported).

    In the SATURN trial (intensive atorvastatin vs. intensive rosuvastatin) new proteinuria was observed in 1.7% and 3.8% of patients assigned to atorvastatin and rosuvastatin respectively. Creatinine greater than ULN was reported in 3% and 3.3% of patients assigned to atorvastatin and rosuvastatin respectively.

    In JUPITER (intensive rosuvastatin vs placebo) any renal related event was reported in 6% of patients assigned to rosuvastatin and 5.4% of placebo. Acute renal failure in 0.2% in both groups and creatinine above ULN in 0.2% and 0.1% respectively and renal failure in 0.3% in both groups.

    TIMI 22 compared 40 mg of pravastatin daily (standard therapy) with 80 mg of atorvastatin daily (intensive therapy) for a mean of two years. No renal adverse outcome was reported as well as no episodes of rhabdomyolysis.

    Interestingly a new RCT presented at the American College of Cardiology’s 62nd Annual Scientific Session showed that high doses (20 mg of rosuvastatin) significantly reduces the rate of acute kidney injury caused by dye used in imaging in acute coronary syndrome patients who underwent a coronary procedure (high risk for kidney damage).

    Clinicians usually use statins to reach LDL cholesterol goals, what can be achieved with different statins and different doses. Based on clinical trial data, no clear evidence of acute renal failure or major renal harm is observed.

    Retrospective analyses of prospective collected data might be a source of misleading conclusions and should be interpreted cautiously and at most “hypothesis generating”; furthermore, the measured first outcome “hospitalization for acute kidney injury” in the present analyses was defined using a validated algorithm and diagnosis codes what might also be a confusing.

    New trials will provide important unbiased data in subjects without prior vascular disease expose to a potent statin. HOPE 4 is still ongoing and will add useful information.