Clinical trial NCT01236274: The Risk of Myocardial Infarction in Users of Antipsychotic Agents
Official title: The Risk of Myocardial Infarction in Users of Antipsychotic Agents: a CALIBER Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Myocardial Infarction
Keywords: Myocardial Infarction
Antipsychotic agents
Self-controlled case series method
General Practice Research Database
Myocardial Ischaemia National Audit Project
CALIBER
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: University College, London
First posted: 2010-11-07
Enrollment: 90000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population is comprised of patients registered at those GPRD practices that agreed to linkage with the MINAP database, and whose practices are "up to standard" according to the GPRD criteria.

Self-controlled Case Series:

Patients who experienced an MI and received an antipsychotic agent during up to standard (UTS) follow-up in the GPRD, will be included and will act as their own control.

Case- control Study:

All cases of first recorded occurrence of an MI, identified by the recording of a Read code in the GPRD within the UTS period until December 2009 will be identified. Five controls for each case will be selected matched by age, gender, General Practitioner and registration in the GPRD on the date of MI of the case.

Brief summary: A number of studies have suggested an association between the use of antipsychotic agents and cardiovascular mortality. However, the relationship between cardiac events and the use of antipsychotic drugs is not clear. Patients experiencing psychoses and in need for antipsychotic agents may be at a higher risk of cardiac events regardless of any effect of antipsychotic medication. Two studies have specifically investigated the association between the use of antipsychotics and the risk of cardiac events using Myocardial Infarction (MI) as an outcome measure, reporting no association and a positive association respectively. This difference in results may be explained by the use of different measures as well as study designs in both studies and because of different limitations with regard to controlling for lifestyle and medical risk factors. This study aims to assess the relationship between the risk of MI and recent exposure to antipsychotic agents by using the self-controlled case series method with which we are able to control for fixed confounders. The results of the self-controlled case series method will be compared to the results of a case-control study using the same data to compare the estimates of both methods.

Detailed description: This study is part of the CALIBER (Cardiovascular disease research using linked bespoke studies and electronic records) programme funded over 5 years from the NIHR and Wellcome Trust. The central theme of the CALIBER research is linkage of the Myocardial Ischaemia National Audit Project (MINAP) with primary care (GPRD) and other resources. The overarching aim of CALIBER is to better understand the aetiology and prognosis of specific coronary phenotypes across a range of causal domains, particularly where electronic records provide a contribution beyond traditional studies. CALIBER has received both Ethics approval (ref 09/H0810/16) and ECC approval (ref ECC 2-06(b)/2009 CALIBER dataset).

The use of antipsychotics is associated with a rise in cardiovascular events. Previous studies investigating the effect of antipsychotic agents on the risk of Myocardial Infarction (MI) led to conflicting results with reports of either no association or a positive association. As patient populations for whom antipsychotic agents are indicated differ considerably from healthy comparison populations, confounding by indication could be substantial. Whilst confounding can be accounted for if known and measured, residual confounding remains a potential problem. This study aims to assess the relationship between the risk of MI and recent exposure to antipsychotic agents by using the self-controlled case series method with which we are able to control for fixed confounders. The results of the self-controlled case series method will be compared to the results of a case-control study using the same data to explore the role of confounding by indication.

Eligibility criteria: Inclusion Criteria:

* Patients in GPRD practices that agreed to linkage with the MINAP database
* Age over 18
* Self-controlled case-series: patients who received an antipsychotic agent during up to standard (UTS) follow-up in the GPRD
* Self-controlled case-series: patients who experienced a first record of MI at least 12 months after the start of UTS follow-up period in the GPRD data record

Exclusion Criteria:

* Patients will be excluded after experiencing their first MI

Primary outcomes:
measure: First occurrence of a myocardial infarction recorded in the patient's medical record
timeFrame: Patients in the General Practice Research database (GPRD) are followed from registration until they leave the practice, die, or 31st of December 2009, whichever occurs first
Secondary outcomes:
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: London School of Hygiene and Tropical Medicine
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Ruth Brauer
role: PRINCIPAL_INVESTIGATOR
affiliation: University College, London
name: Harry Hemingway, FRCP
role: STUDY_DIRECTOR
References: