HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. 2023

David J Tunnicliffe, and Suetonia C Palmer, and Brydee A Cashmore, and Valeria M Saglimbene, and Rathika Krishnasamy, and Kelly Lambert, and David W Johnson, and Jonathan C Craig, and Giovanni Fm Strippoli
Sydney School of Public Health, The University of Sydney, Sydney, Australia.

Cardiovascular disease is the most frequent cause of death in people with early stages of chronic kidney disease (CKD), and the absolute risk of cardiovascular events is similar to people with coronary artery disease. This is an update of a review first published in 2009 and updated in 2014, which included 50 studies (45,285 participants). To evaluate the benefits and harms of statins compared with placebo, no treatment, standard care or another statin in adults with CKD not requiring dialysis. We searched the Cochrane Kidney and Transplant Register of Studies up to 4 October 2023. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. An updated search will be undertaken every three months. Randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of statins with placebo, no treatment, standard care, or other statins, on death, cardiovascular events, kidney function, toxicity, and lipid levels in adults with CKD (estimated glomerular filtration rate (eGFR) 90 to 15 mL/min/1.73 m2) were included. Two or more authors independently extracted data and assessed the study risk of bias. Treatment effects were expressed as mean difference (MD) for continuous outcomes and risk ratios (RR) for dichotomous benefits and harms with 95% confidence intervals (CI). The risk of bias was assessed using the Cochrane risk of bias tool, and the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We included 63 studies (50,725 randomised participants); of these, 53 studies (42,752 participants) compared statins with placebo or no treatment. The median duration of follow-up was 12 months (range 2 to 64.8 months), the median dosage of statin was equivalent to 20 mg/day of simvastatin, and participants had a median eGFR of 55 mL/min/1.73 m2. Ten studies (7973 participants) compared two different statin regimens. We were able to meta-analyse 43 studies (41,273 participants). Most studies had limited reporting and hence exhibited unclear risk of bias in most domains. Compared with placebo or standard of care, statins prevent major cardiovascular events (14 studies, 36,156 participants: RR 0.72, 95% CI 0.66 to 0.79; I2 = 39%; high certainty evidence), death (13 studies, 34,978 participants: RR 0.83, 95% CI 0.73 to 0.96; I² = 53%; high certainty evidence), cardiovascular death (8 studies, 19,112 participants: RR 0.77, 95% CI 0.69 to 0.87; I² = 0%; high certainty evidence) and myocardial infarction (10 studies, 9475 participants: RR 0.55, 95% CI 0.42 to 0.73; I² = 0%; moderate certainty evidence). There were too few events to determine if statins made a difference in hospitalisation due to heart failure. Statins probably make little or no difference to stroke (7 studies, 9115 participants: RR 0.64, 95% CI 0.37 to 1.08; I² = 39%; moderate certainty evidence) and kidney failure (3 studies, 6704 participants: RR 0.98, 95% CI 0.91 to 1.05; I² = 0%; moderate certainty evidence) in people with CKD not requiring dialysis. Potential harms from statins were limited by a lack of systematic reporting. Statins compared to placebo may have little or no effect on elevated liver enzymes (7 studies, 7991 participants: RR 0.76, 95% CI 0.39 to 1.50; I² = 0%; low certainty evidence), withdrawal due to adverse events (13 studies, 4219 participants: RR 1.16, 95% CI 0.84 to 1.60; I² = 37%; low certainty evidence), and cancer (2 studies, 5581 participants: RR 1.03, 95% CI 0.82 to 1.30; I² = 0%; low certainty evidence). However, few studies reported rhabdomyolysis or elevated creatinine kinase; hence, we are unable to determine the effect due to very low certainty evidence. Statins reduce the risk of death, major cardiovascular events, and myocardial infarction in people with CKD who did not have cardiovascular disease at baseline (primary prevention). There was insufficient data to determine the benefits and harms of the type of statin therapy. Statins reduce death and major cardiovascular events by about 20% and probably make no difference to stroke or kidney failure in people with CKD not requiring dialysis. However, due to limited reporting, the effect of statins on elevated creatinine kinase or rhabdomyolysis is unclear. Statins have an important role in the primary prevention of cardiovascular events and death in people who have CKD and do not require dialysis. Editorial note: This is a living systematic review. We will search for new evidence every three months and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

UI MeSH Term Description Entries
D009203 Myocardial Infarction NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION). Cardiovascular Stroke,Heart Attack,Myocardial Infarct,Cardiovascular Strokes,Heart Attacks,Infarct, Myocardial,Infarction, Myocardial,Infarctions, Myocardial,Infarcts, Myocardial,Myocardial Infarctions,Myocardial Infarcts,Stroke, Cardiovascular,Strokes, Cardiovascular
D003404 Creatinine Creatinine Sulfate Salt,Krebiozen,Salt, Creatinine Sulfate,Sulfate Salt, Creatinine
D006435 Renal Dialysis Therapy for the insufficient cleansing of the BLOOD by the kidneys based on dialysis and including hemodialysis, PERITONEAL DIALYSIS, and HEMODIAFILTRATION. Dialysis, Extracorporeal,Dialysis, Renal,Extracorporeal Dialysis,Hemodialysis,Dialyses, Extracorporeal,Dialyses, Renal,Extracorporeal Dialyses,Hemodialyses,Renal Dialyses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000078202 Systematic Reviews as Topic Works about a review of primary literature in health and health policy that attempt to identify, appraise, and synthesize all the empirical evidence that meets specified eligibility criteria to answer a given research question. It's conducted using explicit methods aimed at minimizing bias in order to produce more reliable findings regarding the effects of interventions for prevention, treatment, and rehabilitation that can be used to inform decision making. Systematic Review as Topic,Umbrella Reviews as Topic,Reviews Systematic as Topic
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D012206 Rhabdomyolysis Necrosis or disintegration of skeletal muscle often followed by myoglobinuria. Rhabdomyolyses
D051436 Renal Insufficiency, Chronic Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002) Kidney Insufficiency, Chronic,Chronic Kidney Diseases,Chronic Kidney Insufficiency,Chronic Renal Diseases,Chronic Renal Insufficiency,Chronic Kidney Disease,Chronic Kidney Insufficiencies,Chronic Renal Disease,Chronic Renal Insufficiencies,Disease, Chronic Kidney,Disease, Chronic Renal,Diseases, Chronic Kidney,Diseases, Chronic Renal,Kidney Disease, Chronic,Kidney Diseases, Chronic,Kidney Insufficiencies, Chronic,Renal Disease, Chronic,Renal Diseases, Chronic,Renal Insufficiencies, Chronic
D019161 Hydroxymethylglutaryl-CoA Reductase Inhibitors Compounds that inhibit HYDROXYMETHYLGLUTARYL COA REDUCTASES. They have been shown to directly lower CHOLESTEROL synthesis. HMG-CoA Reductase Inhibitor,HMG-CoA Reductase Inhibitors,Hydroxymethylglutaryl-CoA Reductase Inhibitor,Statin,Statins, HMG-CoA,Inhibitors, HMG-CoA Reductase,Inhibitors, Hydroxymethylglutaryl-CoA,Inhibitors, Hydroxymethylglutaryl-Coenzyme A,Statins,HMG CoA Reductase Inhibitor,HMG CoA Reductase Inhibitors,HMG-CoA Statins,Hydroxymethylglutaryl CoA Reductase Inhibitor,Hydroxymethylglutaryl CoA Reductase Inhibitors,Hydroxymethylglutaryl-CoA Inhibitors,Hydroxymethylglutaryl-Coenzyme A Inhibitors,Inhibitors, HMG CoA Reductase,Inhibitors, Hydroxymethylglutaryl CoA,Inhibitors, Hydroxymethylglutaryl Coenzyme A,Inhibitors, Hydroxymethylglutaryl-CoA Reductase,Reductase Inhibitor, Hydroxymethylglutaryl-CoA,Reductase Inhibitors, HMG-CoA,Reductase Inhibitors, Hydroxymethylglutaryl-CoA,Statins, HMG CoA
D020521 Stroke A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810) Apoplexy,Cerebral Stroke,Cerebrovascular Accident,Cerebrovascular Apoplexy,Vascular Accident, Brain,CVA (Cerebrovascular Accident),Cerebrovascular Accident, Acute,Cerebrovascular Stroke,Stroke, Acute,Acute Cerebrovascular Accident,Acute Cerebrovascular Accidents,Acute Stroke,Acute Strokes,Apoplexy, Cerebrovascular,Brain Vascular Accident,Brain Vascular Accidents,CVAs (Cerebrovascular Accident),Cerebral Strokes,Cerebrovascular Accidents,Cerebrovascular Accidents, Acute,Cerebrovascular Strokes,Stroke, Cerebral,Stroke, Cerebrovascular,Strokes,Strokes, Acute,Strokes, Cerebral,Strokes, Cerebrovascular,Vascular Accidents, Brain

Related Publications

David J Tunnicliffe, and Suetonia C Palmer, and Brydee A Cashmore, and Valeria M Saglimbene, and Rathika Krishnasamy, and Kelly Lambert, and David W Johnson, and Jonathan C Craig, and Giovanni Fm Strippoli
January 2015, Sao Paulo medical journal = Revista paulista de medicina,
David J Tunnicliffe, and Suetonia C Palmer, and Brydee A Cashmore, and Valeria M Saglimbene, and Rathika Krishnasamy, and Kelly Lambert, and David W Johnson, and Jonathan C Craig, and Giovanni Fm Strippoli
April 2009, The Cochrane database of systematic reviews,
David J Tunnicliffe, and Suetonia C Palmer, and Brydee A Cashmore, and Valeria M Saglimbene, and Rathika Krishnasamy, and Kelly Lambert, and David W Johnson, and Jonathan C Craig, and Giovanni Fm Strippoli
May 2014, The Cochrane database of systematic reviews,
David J Tunnicliffe, and Suetonia C Palmer, and Brydee A Cashmore, and Valeria M Saglimbene, and Rathika Krishnasamy, and Kelly Lambert, and David W Johnson, and Jonathan C Craig, and Giovanni Fm Strippoli
April 2009, The Cochrane database of systematic reviews,
David J Tunnicliffe, and Suetonia C Palmer, and Brydee A Cashmore, and Valeria M Saglimbene, and Rathika Krishnasamy, and Kelly Lambert, and David W Johnson, and Jonathan C Craig, and Giovanni Fm Strippoli
October 2004, The Cochrane database of systematic reviews,
David J Tunnicliffe, and Suetonia C Palmer, and Brydee A Cashmore, and Valeria M Saglimbene, and Rathika Krishnasamy, and Kelly Lambert, and David W Johnson, and Jonathan C Craig, and Giovanni Fm Strippoli
September 2013, The Cochrane database of systematic reviews,
David J Tunnicliffe, and Suetonia C Palmer, and Brydee A Cashmore, and Valeria M Saglimbene, and Rathika Krishnasamy, and Kelly Lambert, and David W Johnson, and Jonathan C Craig, and Giovanni Fm Strippoli
July 2009, The Cochrane database of systematic reviews,
David J Tunnicliffe, and Suetonia C Palmer, and Brydee A Cashmore, and Valeria M Saglimbene, and Rathika Krishnasamy, and Kelly Lambert, and David W Johnson, and Jonathan C Craig, and Giovanni Fm Strippoli
January 2014, The Cochrane database of systematic reviews,
David J Tunnicliffe, and Suetonia C Palmer, and Brydee A Cashmore, and Valeria M Saglimbene, and Rathika Krishnasamy, and Kelly Lambert, and David W Johnson, and Jonathan C Craig, and Giovanni Fm Strippoli
April 2009, The Cochrane database of systematic reviews,
David J Tunnicliffe, and Suetonia C Palmer, and Brydee A Cashmore, and Valeria M Saglimbene, and Rathika Krishnasamy, and Kelly Lambert, and David W Johnson, and Jonathan C Craig, and Giovanni Fm Strippoli
November 2006, Nihon rinsho. Japanese journal of clinical medicine,
Copied contents to your clipboard!