Medications and the Risk of Sudden Cardiac Death

NCT ID: NCT00241800

Last Updated: 2017-06-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 1200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2016-05-31

Brief Summary

To investigate a potential relationship between four different classes of non-cardiovascular drugs and the risk of sudden cardiac death.

Detailed Description

BACKGROUND:

There are more than 400,000 sudden cardiac deaths annually in the U.S, of which 85% or more are caused by ventricular tachyarrhythmias. Medications are an important modifiable risk factor because many have effects that can provoke lethal arrhythmias. There is increasing suspicion that several drugs in four widely used classes of non-cardiovascular medications-fluoroquinolone and macrolide antibiotics, antipsychotics, and antidepressants- are pro-arrhythmic and thus increase the risk of sudden cardiac death. Published epidemiologic studies have quantified the risk conferred by older antipsychotics and antidepressants as well as oral erythromycin. The current project will extend these studies to newer medications that are used by an estimated 20% of adults in the U.S. Studies of surrogate markers suggest that the pro-arrhythmic effects of these drugs vary markedly.

DESIGN NARRATIVE:

This retrospective cohort study has three specific aims in testing the relationship between certain non-cardiovascular medications-fluoroquinolone and macrolide antibiotics, antipsychotics, and antidepressants- and sudden cardiac death.. Specific aim 1 tests the hypothesis that there is corresponding variation in risk of sudden cardiac death. In vivo data suggest that concurrent use of study drugs with other common medications that inhibit their metabolism could markedly increase drug concentrations, and thus risk of arrhythmias. Specific aim 2 tests the hypothesis that these pharmacokinetic interactions, defined a priori, increase risk of sudden cardiac death. The hypokalemia caused by the commonly used potassium-wasting diuretics may amplify the pro-arrhythmic effects of medications. Specific aim 3 tests the hypothesis that concurrent use of study drugs and these diuretics increases risk of sudden cardiac death. The investigators will conduct a retrospective cohort study in TennCare, Tennessee's expanded Medicaid program. Computerized TennCare files, linked with death certificates, provide the information necessary to define the cohort, classify followup according to medication exposure and potential confounders, and identify cases of sudden cardiac death using a validated computer case definition we have developed. The cohort will include an estimated 800,000 persons with 15,000 sudden cardiac deaths during 5,000,000 person years of followup and thus will have excellent power for risk estimates. The study will provide data that clinicians need to prescribe these widely used medications in a way that minimizes the risk of sudden cardiac death.

Conditions

Cardiovascular Diseases; Heart Diseases; Death, Sudden, Cardiac; Ventricular Fibrillation

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Patients with life-threatening illnesses will be excluded because for such persons it is not possible to distinguish from deaths related to arrhythmias versus those that are a consequence of the underlying serious illness.

• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Wayne Ray

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wayne Ray

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Other Identifiers

R01HL081707

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1315

Identifier Type: -

Identifier Source: org_study_id