Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases

Dormuth, Colin R.; Hemmelgarn, Brenda R.; Paterson, J Michael; James, Matthew T.; Teare, Gary; Raymond, Colette B; Lafrance, Jean‐Philippe; Levy, Adrian R.; Garg, Amit X.; Ernst, Pierre

doi:10.1136/bmj.f880

Cited by 212 publications

(173 citation statements)

References 22 publications

(17 reference statements)

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“…Dormuth et al evaluated the association between the potency of statins and acute kidney injury (AKI) and noticed 34% higher rate of hospitalization for AKI in the participants on higher compared with lower doses of statins during the first 120 days of treatment [149]. A recent meta-analysis, which included 9 RCTs with 5212 patients with and without acute coronary syndrome evaluated the potential of statins in prevention of contrast-induced acute kidney injury (CI-AKI).…”

Section: Kidney Diseases and Statin Intolerancementioning

confidence: 99%

Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

Banach

Rizzo²,

Tóth

et al. 2015

Expert Opinion on Drug Safety

182

204

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Section: Kidney Diseases and Statin Intolerancementioning

confidence: 99%

Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

Banach

Rizzo²,

Tóth

et al. 2015

Expert Opinion on Drug Safety

182

204

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“…This provoked muscular damage, as was verified by biochemical tests. [3][4][5] However, hypothyroidism and hyperaldosteronism, with consequent hypokalemia and hypocalcemia, can all have contributed to statin-induced myopathy. [6][7][8] Our patient underwent total thyroidectomy 16 years ago because of Graves's disease.…”

Section: Discussionmentioning

confidence: 99%

A dangerous mixture

Piva¹,

Filippi²,

Simioni³

2014

Ital J Med

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Emilia, a 59-year old woman was hospitalized due to fatigue, cramps and paresthesias involving her arms with a spontaneous Trousseau sign (spasm of the wrist and metacarpophalangeal joints, extension of distal and proximal interphalangeal joints, adduction of the fingers). 1,2 Urgent biochemical tests showed hypernatremia (150 mmol/L), hypokalemia (2.3 mmol/L), hypocalcemia (total calcium 7.3 mg/dL, ionized calcium 0.89 mmol/L).Her medical history included: thyroidectomy for Graves's disease, now treated with levothyroxine, vitiligo, mild carotid arteries atherosclerosis treated with acetylsalicylic acid, recently diagnosed hypercholesterolemia treated with simvastatin, started the previous month.On admittance to hospital the patient was alert and collaborative; general examination did not show any particular alteration except for vitiligo and mild hyperreflexia. Blood pressure was high (140/100 mmHg) and other vital parameters were normal.Routine laboratory tests confirmed hypernatremia, hypocalcemia and hypokalemia and showed: metabolic alkalosis (pH 7.50, pCO 2 44 mmHg, HCO 3 34 mmol/L); mild hypomagnesemia (1.54 mg/dL; n.v. 1.58-2.55); albuminemia, phosphatemia, blood urea nitrogen and creatinine were normal, but with slightly increased urinary protein excretion (0.29 g/24 h); urinary excretion of calcium was low (31.2 mg/24 h; n.v. 100-320); urinary sodium excretion was elevated (290 mmol/24 h; n.v. 40-220); urinary excretion of phosphate and potassium was normal; muscle enzymes were very elevated (creatine kinase 2509 U/L; myoglobin 466 ng/mL; aldolase 34.9 UI/L); cortisol and aldosterone level were normal, plasma renin activity was low (0.5 pg/mL in orthostatism and 1.5 pg/mL in clynostatism), thyroid-stimulating hormone (TSH) level was high (22.9 uUI/mL) with normal free thyroxine (FT4) (0.92 ng/dL); parathyroid hormone (PTH) level was high (70.8 pg/mL; n.v. 7-53); vitamin D3 was low (19.2 nmol/L; n.v. 75-100). Blood cell count, plasma osmolarity, C-reactive protein, cholesterol and triglycerides levels were normal.Electrocardiogram (EKG) showed sinus rhythm with normal heart rate (60 bpm), prolongation of QT interval. Chest X-ray was regular, upper and lower limbs electromyography showed only a mild A dangerous mixture ABSTRACTA 59-year old woman was admitted for fatigue and arm paresthesias with Trousseau sign. Her medical history included thyroidectomy and hypercholesterolemia recently treated with simvastatin. Laboratory tests showed severe hypokalemia and hypocalcemia, severe increase in muscle enzymes, metabolic alkalosis; low plasma renin activity, increased thyroid-stimulating hormone, normal free thyroxine, increased parathyroid hormone, decreased vitamin D3; alterations in electrolyte urinary excretion, cortisol and aldosterone were excluded. Hypothesizing a statin-related myopathy, simvastatin was suspended; the patient reported use of laxatives containing licorice. Electrolytes normalized with intravenous supplementation. Among many biochemical alterations, none stands out as a major cause f...

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“…20 This meta-analysis, in which two of us participated (CRD and RWP), was conducted by the Canadian Network for Observational Drug Effect Studies (CNODES), which used a common analytical protocol for each of the 9 included studies. The meta-analysis included approximately 2 million patients who initiated statin therapy, with 24,418 patients hospitalized for AKI during the first 2 years of follow-up.…”

Section: Example 2: Statin Potency and Acute Kidney Injurymentioning

confidence: 99%

“…22,23 The introduction of the original CNODES article in Example 2 describes how a non-significant 35% relative increase in the combined endpoint of acute renal failure (ARF) or a doubling of serum creatinine (SCrx2) was observed in the JUPITER trial. 20,22,23 The trial was stopped early and association with the renal harm remained imprecise; hence the motivation for the CNODES study. The JUPITER data could be used to specify a prior distribution in a Bayesian analysis.…”

Section: Relation To Bayesian Analysismentioning

confidence: 99%

Likelihood ratio meta-analysis: New motivation and approach for an old method

Dormuth

Filion

Platt

2016

Contemporary Clinical Trials

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A 95% confidence interval (CI) in an updated meta-analysis may not have the expected 95% coverage. If a meta-analysis is simply updated with additional data, then the resulting 95% CI will be wrong because it will not have accounted for the fact that the earlier meta-analysis failed or succeeded to exclude the null. This situation can be avoided by using the likelihood ratio (LR) as a measure of evidence that does not depend on type-1 error. We show how an LR-based approach, first advanced by Goodman, can be used in a meta-analysis to pool data from separate studies to quantitatively assess where the total evidence points. The method works by estimating the loglikelihood ratio (LogLR) function from each study. Those functions are then summed to obtain a combined function, which is then used to retrieve the total effect estimate, and a corresponding 'intrinsic' confidence interval. Using as illustrations the CAPRIE trial of clopidogrel versus aspirin in the prevention of ischaemic events, and our own meta-analyses of higher potency statins and the Disclosure and Management of Competing InterestsThe following authors report that they have no competing interests: Colin R. Dormuth, Kristian B. Filion, Robert W. Platt. CopyrightThe Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, a worldwide licence to the Publishers and its licensees in perpetuity, in all forms, formats and media (whether known now or created in the future), to i) publish, reproduce, distribute, display and store the Contribution, ii) translate the Contribution into other languages, create adaptations, reprints, include within collections and create summaries, extracts and/or, abstracts of the Contribution, iii) create any other derivative work(s) based on the Contribution, iv) to exploit all subsidiary rights in the Contribution, v) the inclusion of electronic links from the Contribution to third party material where-ever it may be located; and, vi) licence any third party to do any or all of the above. CIHR Author ManuscriptCIHR Author Manuscript CIHR Author Manuscript risk of acute kidney injury, we show that the LR-based method yields the same point estimate as a traditional analysis, but with an intrinsic confidence interval that is appropriately wider than the traditional 95% CI. The LR-based method can be used to conduct both fixed effect and random effects meta-analyses, it can be applied to old and new meta-analyses alike, and results can be presented in a format that is familiar to a meta-analytic audience.

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Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases

Cited by 212 publications

References 22 publications

Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

A dangerous mixture

Likelihood ratio meta-analysis: New motivation and approach for an old method

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