#Rosuvastatin #risk #kidney #damage
USA – In a large retrospective cohort study, rosuvastatin, used to lower cholesterol levels, was associated with slightly higher risks of kidney damage than atorvastatin, risks that were higher at higher doses.
Rosuvastatin, the most potent statin on the market, has been associated with an excess risk of kidney damage compared to atorvastatin in case reports and small trials, but the topic has received little scrutiny since its approval in 2003.
The current analysis “is one of the first and largest real-world studies” examining the risk of hematuria, proteinuria, and kidney failure with rosuvastatin versus atorvastatin with replacement therapy (dialysis or transplant) for a range of glomerular filtration rate (eGFR) in a heterogeneous population, the researchers write.
“Our results suggest the need for increased caution in patients receiving high doses or who have severe chronic kidney disease (CKD),” said Dr. Dr Jung Im Shin, PhD, assistant professor, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, in an email to Medscape Medical News. She is the lead author of the study published online July 19 in the Journal of the American Society of Nephrology[1].
A high dose compared to recommendations.
The analysis looked at nearly one million patients in the United States who received a first prescription for rosuvastatin or atorvastatin between 2011 and 2019; they were followed for a median of 3.1 years. Among the results:
Rosuvastatin users had an 8% increased risk of hematuria, a 17% increased risk of proteinuria, and a 15% increased risk of kidney failure with replacement therapy, compared to people taking atorvastatin.
Both groups avoided heart attack and stroke in similar proportions.
44% of patients with severe G4+ CKD (eGFR < 30 ml/min/1.73 m2) were prescribed a dose of rosuvastatin higher than the maximum dose of 10 mg/day recommended for these patients by the Food and Drug Administration .US Drug Administration (FDA)
Based on this study, “we don’t know why compliance with the FDA recommendation for rosuvastatin dosing in patients with severe CKD is so low,” said Dr. Shin. “Few physicians are likely to be 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] it may not be worth the risk, even if it’s low, especially with a low eGFR,” he added. “Our study provides an opportunity to raise awareness of this clinical problem.”
“Future studies are warranted to shed light on the discrepancy between real-world practice and FDA dosing recommendations for high-dose rosuvastatin,” the researchers write.
“Greater awareness and education are essential”
invited to comment, Dr Swapnil Hiremathnéphrologue at the Institut de recherche de l’Hôpital d’Ottawa, Ontario, Canada, noted that he risked plus elevé de néphrotoxicité avec la rosuvastatine à forte dos por rapport à l’atorvastatine à forte doses a été montré dans l’ essay PLANET 1 published in 2015 and, for example, in a case report published in 2016, which the researchers also mention.
“I was personally 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 podcaster Freely Filtered, and who is not associated. with the current study.
“We see this from time to time,” he continued, “but because someone is targeting LDL and hasn’t noticed GFR, or maybe the patient started on a high dose a long time ago and kidney function went down, and no one changed the high dose. »
“Increased awareness and better education is essential,” observed Dr. Hiremath. “My personal bias is to have specialist nephrology pharmacists involved in multidisciplinary clinics when the DFG [est] <30 or so,” he added. "There are so many other tough questions about drugs and how they interact" in patients with kidney disease.
However, “I would be careful not to draw too many conclusions from an observational study,” Dr. Hiremath added. “There is always a risk of residual confounding and selection bias,” the researchers acknowledge, “and especially concomitant risks. »
For example, “if there are fewer cardiovascular deaths with rosuvastatin, then more people who survive may develop kidney failure. »
In practice, the dosage is not clear.
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 a 80-mg dose of rosuvastatin was discontinued due to safety signals related to hematuria and proteinuria highlighted at the time of rosuvastatin’s FDA approval.
However, there has been little post-marketing surveillance to assess the real risk of high-dose rosuvastatin, and it remains unclear whether clinical practice adheres to the FDA-recommended starting dose in severe CRF, i.e., 5 mg/day and to what extent. with a maximum of 10 mg/day, the report notes.
The researchers analyzed anonymous electronic medical record data from 40 health care organizations in the United States from the OptumLabs Data Warehouse database. A total of 152,101 new rosuvastatin users and 795,799 new atorvastatin users were enrolled, and patients with a history of rhabdomyolysis were excluded.
Patients in the two groups were similar with respect to CKD prevalence, cardiovascular risk factors, and demographics. Their median age was 60, 48% were female, and 82% were Caucasian.
Hematuria was defined as dipstick hematuria > + or the presence of > 3 red blood cells per high-power field on urine microscopy, at least twice. Proteinuria was defined as dipstick proteinuria > ++ or an albumin/creatinine ratio > 300 mg/g at least twice.
Overall, 2.9% of patients experienced hematuria (3.4% in the rosuvastatin group and 2.8% in the atorvastatin group) and 1% of patients experienced proteinuria (1.2% and 0 .9%, respectively).
After balancing baseline characteristics in both groups using inverse weighting of treatment likelihood, treatment with rosuvastatin, compared with atorvastatin, was associated with a significantly increased risk of hematuria (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 mtwo had approximately a 2-fold increased risk of hematuria and a 9-fold increased risk of proteinuria during follow-up compared with patients with eGFR ≥ 60 mL/min/1.73 mtwo.
Patients with eGFR < 30 ml/min/1.73 mtwo they were commonly prescribed high-dose rosuvastatin (29.9% received the 20 mg dose and 14% received the 40 mg dose), contrary to the SPCs.
Dr. Shin says she has received research funding from the National Institutes of Health and Merck; disclosures by other authors are included in the report. Dr. Hiremath states that she 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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