High Potency Statins and the Risk of Diabetes (Statins-DM)

March 11, 2016 updated by: Canadian Network for Observational Drug Effect Studies, CNODES

Higher Potency Statins and the Risk of New Diabetes: Multicentre, Observational Study of Administrative Databases

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 increased risk of new diabetes when exposed to high potency statins, compared to low potency statins, among patients who had a recent cardiovascular event or procedure.

The investigators will carry out separate population based cohort studies using administrative health care databases in eight jurisdictions in Canada, the US, and the UK. The cohort will be defined by the initiation of a statin, with follow-up until a diagnosis of incident diabetes or a prescription for insulin or an oral antidiabetic medication. The results from the separate sites will be combined in a meta-analysis to provide an overall assessment of the risk of new onset diabetes in subjects starting a statin.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The study objective is to determine whether the use of high potency statins, compared with the use of low potency statins, is associated with an increased risk of incident diabetes following hospitalisation for a cardiovascular event or procedure. The investigators will use a common-protocol approach to conduct retrospective cohort studies using health care data from eight jurisdictions (the Canadian provinces of Alberta, Manitoba, Nova Scotia, Ontario, Quebec, and Saskatchewan, as well as the United States (US) MarketScan and the United Kingdom (UK) Clinical Practice Research Datalink [CPRD]). The Canadian provincial databases contain information on physician billing, diagnoses and procedures from hospital discharge abstracts, and dispensations for prescription drugs at a population level. The CPRD is a clinical database that is representative of the UK population and contains the records for patients seen at over 680 general practitioner practices in the UK; these data will be linked to the Hospital Episode Statistics (HES) database, which contains in-hospital diagnosis and procedure data. US MarketScan includes individuals and their dependents covered by large U.S. employer health insurance plans, and government and public organizations.

Study population

In each jurisdiction, the investigators will assemble a study cohort that includes all patients with a new prescription for a statin (after hospital discharge), including simvastatin, lovastatin, pravastatin, fluvastatin, atorvastatin, and rosuvastatin, from the earliest availability of data at each site to the last date of available data. The date of study cohort entry is defined by the prescription date of the newly-prescribed statin. Patients will be followed from the date of study cohort entry until an event (defined below) or censoring due to death, departure from the database, 24 months after the initiation of statin treatment, a dispensing for cerivastatin, or the end of the study period (31 March 2011 or the last date of data availability at that site), whichever occurs first. Data from Alberta, Ontario, and Nova Scotia will be restricted to patients aged 65 years and older as prescription data are not available for younger patients.

Case-control selection

The cohort defined above will be analyzed using a nested case-control analysis, where cases are defined as a hospitalization for incident diabetes or the prescription for an insulin or an oral antidiabetic medication. Risk set sampling will be used to randomly select up to 10 controls for each case, matched on sex, age (± two years; however, if no controls are available, within five years), and cohort entry (± 90 days).

Exposure assessment

The exposure categories will be separated by statin potency (high vs. low dose), and the duration of current exposure. For all cases and controls, exposure will be defined hierarchically; more specifically, patients who receive both a high and low potency statin within the same exposure category will be classified as high potency statin users. Current use of a high potency statin will be defined by the last prescription for a high dose statin prior to the index date. Current users will be further classified into three mutually exclusive durations of current exposure (≤120, 121-365, and 366-730 days).

Statistical analyses

Conditional logistic regression will be used to estimate the odds ratios and corresponding 95% confidence intervals (CIs) of the association between statin use and the diabetes endpoint, comparing current use of high potency statins to low potency statins. This is considered the primary analysis. Several sensitivity analyses will be performed to assess the robustness of study results and address some of the study limitations. High dimensional propensity scores will be estimated for all patients in the cohorts using logistic regression. Finally, all site-specific estimates will be meta-analyzed using fixed or random-effects models with inverse variance weighting. The amount of between-site heterogeneity will be estimated using the I square statistic.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
136966

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

36 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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 1998 (or one year after the beginning of data availability) and 31 March 2011. The date of study cohort entry is defined by the prescription date of the newly-prescribed statin after hospital discharge.

Description

Inclusion Criteria:

  • Admitted to hospital with a diagnosis (principal or secondary) for acute myocardial infarction or stroke or a procedure for coronary artery bypass graft or percutaneous coronary intervention during their stay in hospital, with no record of a diabetes diagnosis during their hospitalization
  • Receipt of a prescription for a statin within 90 days of hospital discharge
  • 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 or diabetes medication/diagnosis in the previous year

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
High potency statin users
Exposure will be defined as a new prescription for a high dose statin (high doses of rosuvastatin, high doses of atorvastatin, and high doses of simvastatin) between 1 January 1997 and 31 March 2011, 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).
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).
Drug: Simvastatin (≥40 mg)
Current cumulative exposure to high dose simvastatin (ATC C10AA01) will be defined as a prescription for ≥40 mg of simvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-<365 days, or 366-730 days).
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 31 of March 2011, 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).
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).
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).
Drug: Rosuvastatin (<10mg)
Current cumulative exposure to low dose rosuvastatin (ATC C10AA07) will be defined as a prescription for <10mg 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).
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).
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).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of participants with Incident type 2 diabetes
Time Frame: Patients will be followed from the date of study cohort entry until either hospitalization for diabetes or censoring (whichever occurs first), or will be assessed for up to 24 months.
Patients with a first-hospitalization, receiving a principle or secondary diagnosis for diabetes (ICD-9: 250; ICD-10: E10, E11, E12, E13, E14), or a prescription for insulin or an oral antidiabetic medication.
Patients will be followed from the date of study cohort entry until either hospitalization for diabetes or censoring (whichever occurs first), or will be assessed for up to 24 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Canadian Network for Observational Drug Effect Studies, CNODES

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Canadian Institutes of Health Research (CIHR)
Drug Safety and Effectiveness Network, Canada

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Colin Dormuth, M.Sc., Sc.D., Departments of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver,BC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 4, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 7, 2015

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 14, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 11, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Q12-02

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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