Safety and efficacy of atorvastatin in patients with severe renal dysfunction

Holmberg, Benny; Brännström, Mats; Bucht, B; Crougneau, V; Dimény, Emöke; Ekspong, A; Granroth, B; Gröntoft, KC; Hadimeri, Henrik; Ingman, B; Isaksson, B; Johansson, Gerd; Lindberger, Kerstin; Lundberg, Lennart; Mikaelsson, L; Olausson, Eric; Persson, Bengt; Welin, Dag; Wikdahl, Ann Marie; Stegmayr, Bernd

doi:10.1080/00365590510031255

Cited by 23 publications

(15 citation statements)

References 24 publications

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“…Although LDL cholesterol was lowered equally effectively in the 4D study, there was a minor trend at best for an improved outcome with respect to the primary composite end point (cardiac death, fatal myocardial infarction, stroke), which failed to reach statistical significance, however. This finding is in full agreement with a recent small Scandinavian study that found significant lowering of cardiovascular end points in patients with pre-end-stage CKD but no effect whatsoever with the same dose of atorvastatin in the patients who were on hemodialysis (43). The reasons for this unexpected failure to reduce the primary end point despite substantial lowering of LDL cholesterol are unresolved.…”

Section: Effect Of Statins On Cardiovascular Disease In Patients Withsupporting

confidence: 81%

Lipid Changes and Statins in Chronic Renal Insufficiency

Ritz

Wanner

2006

Journal of the American Society of Nephrology

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It has been known for a long time that chronic kidney disease (CKD) is associated with dyslipidemia, but the full extent of abnormalities has been appreciated only recently, because routine laboratory tests fail to disclose the entire spectrum of lipid abnormalities. Lipids, particularly HDL cholesterol, are predictive of cardiovascular events, but a paradoxic inverse relation between cholesterol concentration and cardiovascular death has been noted in uremic patients. This currently is thought to be explained by the confounding effect of microinflammation and possibly calcification, but this is not definitely proved. Several retrospective analyses that included patients with mild or moderate CKD documented benefit from lowering of cholesterol by statins. In contrast, the Die Deutsche Diabetes Dialyse (4D) study and a small Scandinavian study failed to show a benefit from lowering of cholesterol by statins in ESRD. Pathomechanistically, it is possible that nonclassical pathomechanisms override statin-sensitive mechanisms as also suggested by the observation that statins fail to reduce carotid intima-media thickening. Although, experimentally, exposure to lipids (particularly oxidized lipids) aggravates progression, data on the effect of statins on progression in patients with CKD are not definite. The most likely explanation is that the impact of numerous confounders obscures their effect on progression. The increase in urinary protein excretion of patients who are treated with statins had been a cause of concern, but the underlying mechanism (i.e. interference with proximal tubular reabsorption of protein) meanwhile has been well documented.

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Section: Effect Of Statins On Cardiovascular Disease In Patients Withsupporting

confidence: 81%

Lipid Changes and Statins in Chronic Renal Insufficiency

Ritz

Wanner

2006

Journal of the American Society of Nephrology

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“…In addition, another confounding factor could be that a significant proportion of individuals in the placebo arm (about 15%) also received a non-study statin. Nevertheless, similar findings were also reported in a recent small Scandinavian study that showed a significant decrease in cardiovascular end points after atorvastatin administration in patients with predialysis renal failure but no effect in individuals who were on maintenance HD [166]. Several mechanisms have been proposed for the explanation of the failure of statins to improve cardiovascular outcomes in individuals with advanced renal failure.…”

Section: Drug Therapy Of Dyslipidemia In Ckd Patientssupporting

confidence: 65%

Dyslipidemia in Chronic Kidney Disease: An Approach to Pathogenesis and Treatment

Tsimihodimos

Dounousi

Siamopoulos³

2008

Am J Nephrol

123

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“…The primary composite end point (comprising death from cardiac causes, fatal stroke, nonfatal myocardial infarction, or nonfatal stroke) was reduced by 8% (95% confidence interval [CI] 0.77 to 1.10), which was not statistically significant (P ϭ 0.37). These results have recently been confirmed in a small Swedish study where atorvastatin had no significant impact on cardiovascular outcome in dialysis patients (2).…”

supporting

confidence: 68%

The Challenge of Sudden Death in Dialysis Patients

Ritz¹,

Wanner²

2008

Clinical Journal of the American Society of Nephrology

114

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A 60-yr-old patient with ESRD (82 kg/168 cm), hypertension for the previous 18 yr, and type 2 diabetes is found dead in bed by his wife at home on a Saturday morning. The patient's history is notable for having started dialysis 34 weeks previously. His last dialysis had been the previous day (on a Friday afternoon). Predialysis potassium had been 5.7 mmol/L, the dialysate K ϩ was 2.0 mmol/L, and Mg 2ϩ was 0.5 mmol/L. Autopsy was not performed.Before his morbid event, the patient had been doing well on dialysis. He had less than 6 episodes of hypotension (Ͻ100 mmHg) per month. His average predialytic weight gain was 4 kg, and, with fluctuations, his average predialysis BP was 155/65 mmHg. While continuing on gliquidone (an oral sulfonylurea hypoglycemic drug that does not accumulate in renal failure), he had no episodes of hypoglycemia, and his last glycosylated hemoglobin level was 7.2%. His medical history is of hypertension, type 2 diabetes, and left ventricular hypertrophy (LVH) with an ejection fraction of 55%. His electrocardiogram showed signs of LVH and flat T waves. He had no history of hypoglycemic episodes and no evidence of retinopathy. He reported no episodes of arrhythmia or precordial pain. A predialysis chest x-ray 2 wk before the terminal event had shown pulmonary congestion. His medications included 0.25 g/d calcitriol, calcium carbonate, 10 mg of folate, 80 mg of verapamil, and no ␤ blockers. In addition, he received varying doses of darbepoietin and iron gluconate as required. He did not receive a statin. Dr. Eberhard Ritz: This case, unfortunately, is the usual presentation of patients on dialysis who succumb to sudden death: There are few, if any, specific premonitory symptoms or signs, cardiac standstill is usually the presenting symptom, and autopsy is not performed, so more specific information on underlying cardiac pathology, if any, is not available. The lack of pathoanatomic confirmation of the underlying pathology or pathologies-as in this case-continues to remain a problem that in the future should come onto the radar screen of nephrologists.Nevertheless, this case presentation raises a number of unresolved issues and provides an occasion to discuss how the currently unsatisfactory results might be improved in the future. In this context, it is of interest to have a look at the recent 4D study.

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Safety and efficacy of atorvastatin in patients with severe renal dysfunction

Abstract: Although the medication caused no severe adverse events, we recommend caution when using atorvastatin for severe CKD patients until further evidence of its safety and efficacy is verified.

Cited by 23 publications

References 24 publications

Lipid Changes and Statins in Chronic Renal Insufficiency

Lipid Changes and Statins in Chronic Renal Insufficiency

Dyslipidemia in Chronic Kidney Disease: An Approach to Pathogenesis and Treatment

The Challenge of Sudden Death in Dialysis Patients

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