Rosuvastatin linked to the risk of kidney damage

UNITED STATES – In a large retrospective cohort study, rosuvastatin, used to lower cholesterol, was associated with a slightly higher risk of kidney damage than atorvastatin, which was greater at higher doses.

Rosuvastatin, the most potent statin on the market, has been linked to an increased risk of kidney damage compared to atorvastatin in case reports and small studies, but the issue has received little study since its approval in 2003.

The current analysis “is one of the first and largest real-world studies” evaluating rosuvastatin versus atorvastatin for the risk of hematuria, proteinuria, and renal failure with replacement therapy—dialysis or transplantation—for a range of estimated glomerular filtration rates (eGFR) in a heterogeneous population , the researchers write.

“Our results suggest that greater caution is needed in patients who receive high doses or who have severe chronic kidney disease (CKD),” he said dr Jung-Im Shin, PhD, assistant professor at the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, in an email to Medscape Medical News. She is the lead author of the study, which was published online July 19 in the Journal of the American Society of Nephrology[1].

A high dosage compared to the recommendations

The analysis looked at nearly one million patients in the United States who received a prescription for rosuvastatin or atorvastatin for the first time between 2011 and 2019; they were followed for a median of 3.1 years. Among the results:

Rosuvastatin users had an 8% greater risk of hematuria, a 17% greater risk of proteinuria, and a 15% greater risk of renal failure on replacement therapy compared to people taking atorvastatin.

Both groups avoided myocardial infarction and stroke in similar proportions.

Forty-four percent of patients with severe G4+ CKD (eGFR < 30 mL/min/1.73 m2) were prescribed a dose of rosuvastatin in excess of the Food and Drug Administration's maximum recommended dose of 10 mg/day for these patients. FDA)

Based on this study, “we do not know why compliance with the FDA recommendation for rosuvastatin dosing in patients with severe chronic kidney disease is so low,” said Dr. shin “Probably few physicians are aware of the dosing recommendations for rosuvastatin [en cas d’IRC sévère], or the potential risks of hematuria or proteinuria. »

“High-dose rosuvastatin [et ses avantages cardiovasculaires] may not be worth the risk, even if it is low, especially with low eGFR,” she added. “Our study provides an opportunity to raise awareness of this clinical issue.”

“Future studies are warranted to shed light on the discrepancy between real-world practice and FDA dosing recommendations for high-dose rosuvastatin,” the researchers state.

“Increased awareness and education are essential”

Invited to comment dr Swapnil Hirematha nephrologist at the Ottawa Hospital Research Institute, Ontario, Canada, noted that the test showed the higher risk of nephrotoxicity with high-dose rosuvastatin compared to high-dose atorvastatin PLANET 1 Published in 2015 and, for example, in a case report published in 2016 – which the researchers also mention.

“Personally, I was surprised” by the high proportion of patients with severe CKD who received higher than recommended doses of rosuvastatin, said Dr. Hiremath, who is also an associate professor at the University of Ottawa and a Freely Filtered podcaster, and is not associated with the current study.

“We see this occasionally,” he continued, “but either because someone is targeting LDL and hasn’t noted the GFR, or maybe the patient started on a high dose some time ago.” a long time and kidney function has subsided, and no one changed the high dose. »

“Greater awareness and better education are imperative,” noted Dr. Hiremath. “My personal preference is to employ pharmacists specializing in nephrology in the multidisciplinary clinics of the DFG [est] < 30 or so,” he added. "There are so many other tricky questions about drugs and how they interact" in patients with kidney disease.

Still, “I would be careful not to draw too many conclusions from an observational study,” added Dr. Added Hiremath. “There is always a risk of residual confounding and selection bias,” which the researchers acknowledge, “and especially attendant risks. »

For example: “If there are fewer cardiovascular deaths on rosuvastatin, more people who survive may develop kidney failure. »

In practice, the dosage is unclear

Atorvastatin at doses of 40 and 80 mg and rosuvastatin at 20 and 40 mg are the only two statins considered high-intensity, the researchers note.

Development of an 80 mg dose of rosuvastatin was halted due to safety signals related to hematuria and proteinuria that were highlighted at the time of rosuvastatin’s FDA approval.

However, there has been little post-marketing surveillance to assess the true risk of high-dose rosuvastatin treatment, and it remains unclear whether and to what extent clinical practice is adhering to the FDA recommended starting dose for severe CKD, ie 5 mg/day , sticking to a maximum of 10 mg/day, the report notes.

Researchers analyzed anonymized electronic medical record data from 40 healthcare organizations across the United States from the OptumLabs Data Warehouse database. They enrolled 152,101 new rosuvastatin users and 795,799 new atorvastatin users and excluded patients with a history of rhabdomyolysis.

Patients in the two groups were similar in terms of CKD prevalence, cardiovascular risk factors, and demographics. Their mean age was 60 years, 48% were female and 82% were Caucasian.

Hematuria was defined as dipstick hematuria > + or the presence of > 3 erythrocytes per high-power field in urine microscopy, at least twice. Proteinuria was defined as dipstick proteinuria > ++ or an albumin/creatinine ratio > 300 mg/g at least twice.

Overall, hematuria occurred in 2.9% of patients (3.4% in the rosuvastatin group and 2.8% in the atorvastatin group) and proteinuria in 1% of patients (1.2% and 0.9%).

After balancing baseline characteristics in both groups using inverse treatment probability weighting, treatment with rosuvastatin was associated with a significantly higher risk of hematuria compared to atorvastatin (hazard ratio [HR]1.08), proteinuria (HR, 1.17), and renal failure requiring replacement therapy (HR, 1.15).

Patients with eGFR < 30 mL/min/1.73 m2 had an approximately 2-fold increased risk of hematuria and a 9-fold increased risk of proteinuria during follow-up compared to patients with eGFR ≥ 60 mL/min/1.73 m2.

Patients with an eGFR < 30 mL/min/1.73 m2 high-dose rosuvastatin was commonly prescribed contrary to the SPCs (29.9% received the 20 mg dose and 14% received the 40 mg dose).

dr Shin says she received research grants from the National Institutes of Health and Merck; Information from other authors is included in the report. dr Hiremath states that he has no relevant financial relationship.

The article originally appeared on Medscape.fr under the title Rosuvastatin Again Linked With Risks to Kidneys. Translated by Stephanie Lavaud.

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