Study stopped early because statins increased the risk of acute kidney injury in patients with kidney disease

This study was published in the Journal of the American Medical Association 2016 Mar 1;315(9):877-88

 

Study title and authors:

High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial.

Billings FT 4th, Hendricks PA, Schildcrout JS, Shi Y, Petracek MR, Byrne JG, Brown NJ.

Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/26906014

This study investigated the relationship between short-term high-dose perioperative atorvastatin and acute kidney injury following cardiac surgery. The study included 615 patients (199 statin-naïve and 416 statin-using) and 308 of these were randomized to atorvastatin and 307 to placebo. The average patient age was 67 years.
(i) Patients naive to statin treatment were randomly assigned 80 mg of atorvastatin the day before surgery, 40 mg of atorvastatin the morning of surgery, and 40 mg of atorvastatin daily following surgery or matching placebo.
(ii) Patients already taking a statin prior to study enrolment continued taking the preenrollment statin until the day of surgery, were randomly assigned 80 mg of atorvastatin the morning of surgery and 40 mg of atorvastatin the morning after or matching placebo, and resumed taking the previously prescribed statin on postoperative day 2.

The study found:
(a) After an interim review, the data and safety monitoring board recommended stopping the group naive to statin treatment due to a 235% increased risk of acute kidney injury among these participants with chronic kidney disease receiving atorvastatin.
(b) After a further review, the data and safety monitoring board later recommended stopping for futility, as the data revealed statins were increasing the risk of acute kidney injury by 6% overall and by 61% in statin naïve patients.
(c) Those who took statins had a 25% increased risk of the more serious stage 2 or stage 3 acute kidney injury compared to those who did not take statins.

The study also revealed:
(d) Those given the statins had a 20% increased risk of muscle pain compared to those taking placebo.
(e) Those given the statins had a 44% increased risk of stroke compared to those taking placebo.
(f) Those given the statins had a 11% increased risk of atrial fibrillation compared to those taking placebo.
(g) Those given the statins had a 202% increased risk of in hospital death compared to those taking placebo.

Links to other studies:
Statins increase the risk of diabetes in kidney transplant patients
Statin use is associated with a 30-36% increased incidence of acute and chronic kidney disease
Statin use associated with a 59% increased risk of kidney failure

Statin use associated with a 59% increased risk of kidney failure

This study was published in the European Journal of Internal Medicine 2016 Feb 23. pii: S0953-6205(16)00059-5

 

Study title and authors:

Association of statin use and the risk of end-stage renal disease: A nationwide Asian population-based case-control study.

Lin SY, Lin CL, Hsu WH, Lin CC, Chang CT, Kao CH.

Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taiwan; Division of Nephrology and Kidney Institute, China Medical University Hospital, Taichung, Taiwan.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/26920930

End-stage renal disease (ESRD), also called kidney failure, is the last stage of chronic kidney disease. When your kidneys fail, it means they have stopped working well enough for you to survive without dialysis or a kidney transplant.

This study investigated the association of statins with end-stage renal disease. The study included 11,486 patients with end-stage renal disease who were compared with the same number of people from the general population.

The study found:
(a) Statin users had a 59% increased risk of developing end-stage renal disease compared to non-users.
(b) The risk of end-stage renal disease increased with higher accumulative dosage of statins.

Lin concluded: "This population-based case-control study showed that statin use might be associated with increased ESRD risks."

Links to other studies:
Statin use is associated with a 30-36% increased incidence of acute and chronic kidney disease
Statins associated with 30% increased risk of death in kidney transplant patients
Statins increase the risk of diabetes in kidney transplant patients

Statins associated with 30% increased risk of death in kidney transplant patients

This paper was published in the Cochrane Database of Systemic Reviews 2009 Apr 15;(2):CD005019

 

Study title and authors:

HMG CoA reductase inhibitors (statins) for kidney transplant recipients.

Navaneethan SD, Perkovic V, Johnson DW, Nigwekar SU, Craig JC, Strippoli GF.

Department of Nephrology and Hypertension, Glickman Urological and Kidney institute, Cleveland Clinic, Cleveland, OH 44195, USA. navanes@ccf.org

 

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/19370615

This paper assessed the effects of statin therapy on kidney transplant recipients. The paper analysed the results of 14 studies with 3,045 participants that compared death rates of patients.

The analysis found that kidney transplant patients that received statins had a 30% increased risk of death compared to patients who did not take statins. 

Statin use is associated with a 30-36% increased incidence of acute and chronic kidney disease

This study was published in the American Journal of Cardiology December 01, 2015

Study title and authors:
Statin Use and the Risk of Kidney Disease With Long-Term Follow-Up (8.4-Year Study)
Tushar Acharya, MD, Jian Huang, MD, Steven Tringali, DO, Christopher R. Frei, PharmD, MSc, Eric M. Mortensen, MD, MSc, Ishak A. Mansi, MD
This study can be accessed at: http://www.ajconline.org/article/S0002-9149(15)02315-2/abstract

The objective of this study was to determine the association of statin use with incidence of acute and chronic kidney diseases. The study lasted for 8.4 years and included 43,438 individuals, (average age 56 years): 13,626 statin users and 29,812 nonusers. In the study the researchers matched 6,342 statin users with 6,342 nonusers.

The study found:
(a) Statin users had a 30% increased risk of acute kidney injury compared to non-users.
(b) Statin users had a 36% increased risk of chronic kidney disease compared to non-users.
(c) Statin users had a 35% increased risk of nephritis/nephrosis/renal sclerosis compared to non-users.

In a separate analysis, the researchers also matched 3,351 "healthy" statin users with 3,351 nonusers. At the start of the study these individuals were all free of diabetes, chronic kidney disease, cardiovascular disease, and conditions that might limit life expectancy or physical activity.

(d) This separate analysis found that these initially "healthy" statin users had a 53% increased risk of developing chronic kidney disease compared to non-users.

Acharya concluded: "Statin use is associated with increased incidence of acute and chronic kidney disease."

Links to other studies:
Statins increase the risk of diabetes in kidney transplant patients
NSAIDs and statins increase the risk of renal cell carcinoma
The unintended adverse effects of statins in men and women



From a fish tank injury to hospital haemodialysis: the serious consequences of statin drug interactions

This paper was published in BMJ Case Reports 2015 Jun 23;2015

 

Study title and authors:

From a fish tank injury to hospital haemodialysis: the serious consequences of drug interactions.

Hill FJ, McCloskey SJ, Sheerin N.

Renal Department, Newcastle Upon Tyne Hospitals, Newcastle Upon Tyne, UK.

 

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/26106178

This paper describes the case of a man who suffered acute kidney injury following statin-induced rhabdomyolysis.

(i) A 68-year-old man was admitted to hospital with severe acute kidney injury secondary to statin-induced rhabdomyolysis.
(ii) Five weeks previously, the patient started a course of clarithromycin for infection of a finger wound. His current medications included simvastatin, which he continued along with clarithromycin.
(iii) The severity of the acute kidney injury necessitated initial continuous venovenous haemofiltration followed by 12 haemodialysis sessions before a spontaneous improvement in renal function occurred.

Hill concluded: "Statins are widely prescribed and we report this case to encourage increased vigilance in avoiding drug interactions known to increase the risk of statin-induced myopathy, including macrolide antibiotics, calcium channel antagonists and amiodarone".

Statins increase the risk of diabetes in kidney transplant patients

This study was published in Transplantation 2013 Nov 26

 

Study title and authors:

HMG CoA Reductase Inhibitor Treatment Induces Dysglycemia in Renal Allograft Recipients.

Choe EY, Wang HJ, Kwon O, Cho Y, Huh KH, Kim MS, Kim YS, Ahn CW, Cha BS, Lee HC, Kang ES.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/24285338

The aim of this study was to evaluate the influence of statins on the development of dysglycemia in kidney transplant patients. (Dysglycemia is defined as diabetes and impaired fasting glucose). The study included 394 patients without previously known diabetes or impaired fasting glucose who had undertaken kidney transplantation. Patients were grouped into the two groups according if they used statins (245 statin users and 149 nonusers).

The study found:
(a) Statin users had a 208% increased risk of dysglycemia compared to non users.
(b) The time to development of dysglycemia after transplantation was shorter in the statin group (38.8 months) than in the control group (47.2 months).

Choe concluded: "Statin treatment is associated with an elevation in fasting plasma glucose and in the development of dysglycemia in renal allograft recipients (kidney transplant patients)".

2% increased risk of death for patients with kidney disease who take statins

This study was published in the Lancet 2011 Jun 25;377(9784):2181-92

 

Study title and authors:

The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial.

Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, Wanner C, Krane V, Cass A,

Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, UK.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/21663949/

This study investigated the effect of a daily dose of simvastatin 20 mg plus ezetimibe 10 mg in patients with chronic kidney disease. This randomised double-blind trial included 9,270 patients with chronic kidney disease (3,023 on dialysis and 6,247 not) with no known history of myocardial infarction or coronary revascularisation. The trial lasted for 4.9 years and 4,650 patients were assigned to receive simvastatin plus ezetimibe and 4,620 to placebo.

The study found that patients who received simvastatin plus ezetimibe had a 2% increased risk of death compared to the patients who received placebo.