High Potency Statins and Acute Kidney Injury

NCT02518516 | Completed

• 1 other identifier: CNODES_Demo_1
• Study Type: observational
• Target: 2,067,639
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypercholesterolemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of patients hospitalized for acute kidney injury

  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.

  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.

Study Arms (2)

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); Drug: Atorvastatin (≥20 mg); Drug: Simvastatin (≥40 mg)

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; Drug: Pravastatin; Drug: Lovastatin; Drug: Atorvastatin (<20mg); Drug: Simvastatin (<40 mg)

Interventions

Rosuvastatin (≥10 mg) DRUG

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).

High potency statin users

Atorvastatin (≥20 mg) DRUG

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).

High potency statin users

Simvastatin (<40 mg) DRUG

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).

Low potency statin users

Fluvastatin DRUG

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).

Low potency statin users

Pravastatin DRUG

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).

Low potency statin users

Lovastatin DRUG

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).

Low potency statin users

Atorvastatin (<20mg) DRUG

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).

Low potency statin users

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Canadian Network for Observational Drug Effect Studies, CNODES: lead
• Drug Safety and Effectiveness Network, Canada: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Dept. of Anesthesiology, Pharmacology & Therapeutics (APT), University of British Columbia

Vancouver, British Columbia, V6T 1Z3, Canada

Location

Related Publications (1)

• 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.

  PMID: 23511950 RESULT

Related Links

• This organization's website describing general functions, other CNODES projects, and investigator profiles.

MeSH Terms

Conditions

Hypercholesterolemia; Acute Kidney Injury; Kidney Diseases; Renal Insufficiency

Interventions

Rosuvastatin Calcium; Atorvastatin; Simvastatin; Fluvastatin; Pravastatin; Lovastatin

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrroles; Azoles; Heptanoic Acids; Fatty Acids; Lipids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Colin Dormuth, M.Sc., Sc.D.

  Departments of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver,BC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2015
• First Posted: August 7, 2015
• Study Start: January 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: March 14, 2016

Record last verified: 2015-08

Locations

CA (1)