High Potency Statins and Acute Kidney Injury

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ClinicalTrials.gov Identifier: NCT02518516

Recruitment Status : Completed

First Posted : August 7, 2015

Last Update Posted : March 14, 2016

Sponsor:

Collaborators:

Drug Safety and Effectiveness Network, Canada

Canadian Institutes of Health Research (CIHR)

Information provided by (Responsible Party):

Canadian Network for Observational Drug Effect Studies, CNODES

Study Description

Brief Summary:

Statins are a class of cholesterol lowering medications that are prescribed for the prevention and treatment of cardiovascular disease. The purpose of this study is to determine if there is an excess risk of acute kidney injury (AKI) with high potency statins compared to low potency statins.

The investigators will carry out separate population based cohort studies using administrative health care databases in nine jurisdictions in Canada, the US, and the UK. Cohorts will be defined by the initiation of a statin, with follow-up until hospitalization for AKI. Analyses will be done separately for groups of patients with and without chronic kidney disease. The results from the separate sites will be combined in a meta-analysis to provide an overall assessment of the risk of AKI in new statin users.

Condition or disease	Intervention/treatment
Hypercholesterolemia	Drug: Rosuvastatin (≥10 mg) Drug: Atorvastatin (≥20 mg) Drug: Simvastatin (≥40 mg) Drug: Fluvastatin Drug: Pravastatin Drug: Lovastatin Drug: Atorvastatin (<20mg) Drug: Simvastatin (<40 mg)

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Study Design

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Study Type :	Observational
Actual Enrollment :	2067639 participants
Observational Model:	Cohort
Time Perspective:	Retrospective
Official Title:	Use of High Potency Statins and Rates of Admission for Acute Kidney Injury: Multicenter, Retrospective Observational Analysis of Administrative Databases
Study Start Date :	January 2011
Actual Primary Completion Date :	January 2013
Actual Study Completion Date :	January 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cholesterol Cholesterol Levels: What You Need to Know Cholesterol Medicines Statins

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
High potency statin users Exposure will be defined as a new prescription for a high dose statin (rosuvastatin, high doses of atorvastatin, and high doses of simvastatin between 1 January 1997 and 30 of April 2008, or 1 year after the beginning of data availability.	Drug: Rosuvastatin (≥10 mg) Current cumulative exposure to high dose rosuvastatin (ATC C10AA07) will be defined as a prescription for ≥10 mg of rosuvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days). Past exposure to high dose rosuvastatin (ATC C10AA07) will be defined as a prescription for ≥10 mg of rosuvastatin dispensed >120 days of the index date (i.e. no exposure within 120 days of the index date). Drug: Atorvastatin (≥20 mg) Current cumulative exposure to high dose atorvastatin (ATC C10AA05) will be defined as a prescription for ≥20 mg of atorvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days). Past exposure to high dose atorvastatin (ATC C10AA05) will be defined as a prescription for ≥20 mg of atorvastatin dispensed >120 days prior to the index date (i.e. no exposure within 120 days of the index date). Drug: Simvastatin (≥40 mg) Current cumulative exposure to high dose simvastatin (ATC C10AA01) will be defined as a prescription for ≥40 mg simvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days). Past exposure to high dose simvastatin (ATC C10AA01) will be defined as a prescription for ≥40 mg simvastatin dispensed >120 days prior to the index date (i.e. no exposure within 120 days of the index date).
Low potency statin users Exposure will be defined as a new prescription for a low dose statin (all doses of fluvastatin, all doses of pravastatin, all doses of lovastatin; low doses of atorvastatin and simvastatin) between 1 January 1997 and 30 of April 2008, or 1 year after the beginning of data availability.	Drug: Fluvastatin Current cumulative exposure to fluvastatin (ATC C10AA04) will be defined as a prescription for any dose of fluvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days). Past exposure to fluvastatin (ATC C10AA04) will be defined as a prescription for any dose of fluvastatin dispensed >120 days prior to the index date (i.e. no exposure within 120 days of the index date). Drug: Pravastatin Current cumulative exposure to pravastatin (ATC C10AA03) will be defined as a prescription for any dose of pravastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days). Past exposure to pravastatin will be defined as a prescription for any dose of pravastatin (ATC C10AA03) dispensed >120 days prior to the index date (i.e. no exposure within 120 days of the index date). Drug: Lovastatin Current cumulative exposure to lovastatin (ATC C10AA02) will be defined as a prescription for any dose of lovastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days). Past exposure to lovastatin will be defined as a prescription for any dose of lovastatin (ATC C10AA02) dispensed >120 days prior to the index date (i.e. no exposure within 120 days of the index date). Drug: Atorvastatin (<20mg) Current cumulative exposure to low dose atorvastatin (ATC C10AA05) will be defined as a prescription for <20 mg of atorvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days). Past exposure to low dose atorvastatin (ATC C10AA05) will be defined as a prescription for <20 mg of atorvastatin dispensed >120 days prior to the index date (i.e. no exposure within 120 days of the index date). Drug: Simvastatin (<40 mg) Current cumulative exposure to low dose simvastatin (ATC C10AA01) will be defined as a prescription for <40 mg simvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days). Past exposure to low dose simvastatin (ATC C10AA01) will be defined as a prescription for <40 mg simvastatin dispensed >120 days prior to the index date (i.e. no exposure within 120 days of the index date).

Group/Cohort

Intervention/treatment

High potency statin users

Exposure will be defined as a new prescription for a high dose statin (rosuvastatin, high doses of atorvastatin, and high doses of simvastatin between 1 January 1997 and 30 of April 2008, or 1 year after the beginning of data availability.

Drug: Rosuvastatin (≥10 mg)

Current cumulative exposure to high dose rosuvastatin (ATC C10AA07) will be defined as a prescription for ≥10 mg of rosuvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days).

Past exposure to high dose rosuvastatin (ATC C10AA07) will be defined as a prescription for ≥10 mg of rosuvastatin dispensed >120 days of the index date (i.e. no exposure within 120 days of the index date).

Drug: Atorvastatin (≥20 mg)

Current cumulative exposure to high dose atorvastatin (ATC C10AA05) will be defined as a prescription for ≥20 mg of atorvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days).

Past exposure to high dose atorvastatin (ATC C10AA05) will be defined as a prescription for ≥20 mg of atorvastatin dispensed >120 days prior to the index date (i.e. no exposure within 120 days of the index date).

Drug: Simvastatin (≥40 mg)

Current cumulative exposure to high dose simvastatin (ATC C10AA01) will be defined as a prescription for ≥40 mg simvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days).

Past exposure to high dose simvastatin (ATC C10AA01) will be defined as a prescription for ≥40 mg simvastatin dispensed >120 days prior to the index date (i.e. no exposure within 120 days of the index date).

Low potency statin users

Exposure will be defined as a new prescription for a low dose statin (all doses of fluvastatin, all doses of pravastatin, all doses of lovastatin; low doses of atorvastatin and simvastatin) between 1 January 1997 and 30 of April 2008, or 1 year after the beginning of data availability.

Drug: Fluvastatin

Current cumulative exposure to fluvastatin (ATC C10AA04) will be defined as a prescription for any dose of fluvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days).

Past exposure to fluvastatin (ATC C10AA04) will be defined as a prescription for any dose of fluvastatin dispensed >120 days prior to the index date (i.e. no exposure within 120 days of the index date).

Drug: Pravastatin

Current cumulative exposure to pravastatin (ATC C10AA03) will be defined as a prescription for any dose of pravastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days).

Past exposure to pravastatin will be defined as a prescription for any dose of pravastatin (ATC C10AA03) dispensed >120 days prior to the index date (i.e. no exposure within 120 days of the index date).

Drug: Lovastatin

Current cumulative exposure to lovastatin (ATC C10AA02) will be defined as a prescription for any dose of lovastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days).

Past exposure to lovastatin will be defined as a prescription for any dose of lovastatin (ATC C10AA02) dispensed >120 days prior to the index date (i.e. no exposure within 120 days of the index date).

Drug: Atorvastatin (<20mg)

Current cumulative exposure to low dose atorvastatin (ATC C10AA05) will be defined as a prescription for <20 mg of atorvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days).

Past exposure to low dose atorvastatin (ATC C10AA05) will be defined as a prescription for <20 mg of atorvastatin dispensed >120 days prior to the index date (i.e. no exposure within 120 days of the index date).

Drug: Simvastatin (<40 mg)

Current cumulative exposure to low dose simvastatin (ATC C10AA01) will be defined as a prescription for <40 mg simvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-365 days, or 366-730 days).

Past exposure to low dose simvastatin (ATC C10AA01) will be defined as a prescription for <40 mg simvastatin dispensed >120 days prior to the index date (i.e. no exposure within 120 days of the index date).

Outcome Measures

Primary Outcome Measures :

Number of patients hospitalized for acute kidney injury [ Time Frame: Patients will be followed from the date of study cohort entry until either hospitalization for acute kidney injury or censoring (whichever occurs first), or will be assessed for up to 24 months. ]
Patients hospitalized for acute kidney injury (including but not limited to hypertensive renal disease with renal failure, chronic glomerulonephiritis, and renal sclerosis) with any of the following diagnostic codes: ICD-9 584, 584.5, 584.6, 584.7, 584.8, or 584.9; ICD-10 N17, N17.0, N17.1, N17.2, N17.8, or N17.9.

Eligibility Criteria

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Ages Eligible for Study:	40 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

In each jurisdiction, the investigators will assemble a study cohort that includes all patients with a new prescription for a statin, including simvastatin, lovastatin, pravastatin, fluvastatin, atorvastatin, and rosuvastatin between 1 January 1997 (or one year after the beginning of data availability) and 30 April 2008. The date of study cohort entry is defined by the prescription date of the newly-prescribed statin. Two separate cohorts will be created based on the presence or absence of a history of chronic kidney disease.

Criteria

Inclusion Criteria:

Patients with a new prescription for a statin from the earliest availability of data at each site to the last date of availability of data +365 days
Patients who are at least 40 years of age at cohort entry
Patients with at least one year of history in the database

Exclusion Criteria:

Patients under the age of 40 (<66 in jurisdictions with drug data for seniors only)
Patients with less than one year of history in the database
Patients who received any cholesterol lowering drugs (including fibrates, niacin and ezetimibe) or underwent dialysis or a kidney transplant in the previous year

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02518516

Locations

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Canada, British Columbia
Dept. of Anesthesiology, Pharmacology & Therapeutics (APT), University of British Columbia
Vancouver, British Columbia, Canada, V6T 1Z3

Sponsors and Collaborators

Canadian Network for Observational Drug Effect Studies, CNODES

Drug Safety and Effectiveness Network, Canada

Canadian Institutes of Health Research (CIHR)

Investigators

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Principal Investigator:	Colin Dormuth, M.Sc., Sc.D.	Departments of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver,BC

More Information

Additional Information:

This organization's website describing general functions, other CNODES projects, and investigator profiles. This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

Publications of Results:

Dormuth CR, Hemmelgarn BR, Paterson JM, James MT, Teare GF, Raymond CB, Lafrance JP, Levy A, Garg AX, Ernst P; Canadian Network for Observational Drug Effect Studies. Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases. BMJ. 2013 Mar 18;346:f880. doi: 10.1136/bmj.f880.

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Responsible Party:	Canadian Network for Observational Drug Effect Studies, CNODES
ClinicalTrials.gov Identifier:	NCT02518516 History of Changes
Other Study ID Numbers:	CNODES_Demo_1
First Posted:	August 7, 2015 Key Record Dates
Last Update Posted:	March 14, 2016
Last Verified:	August 2015

Keywords provided by Canadian Network for Observational Drug Effect Studies, CNODES:


Statins, HMG-CoA Acute kidney injury Kidney diseases Renal failure

Additional relevant MeSH terms:

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Hypercholesterolemia Acute Kidney Injury Hyperlipidemias Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases Renal Insufficiency Kidney Diseases Urologic Diseases Atorvastatin Rosuvastatin Calcium Simvastatin	Pravastatin Lovastatin L 647318 Dihydromevinolin Hydroxymethylglutaryl-CoA Reductase Inhibitors Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Enzyme Inhibitors

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