Patient Characteristics, Persistence to Treatment and Outcome Events in Patients Treated With Ticagrelor 60 mg After Myocardial Infarction in Real-world Clinical Practice (ALETHEIA)

An Observational, Register-based Study on Ticagrelor 60 mg Persistence and Event Rates in Clinical Practice in the US and Europe.

This is an observational study based on secondary data extracted from multiple register-based data sources in the US and Europe (Sweden, United Kingdom, Italy, Germany). The study will include patients initiating treatment with ticagrelor 60 mg after a myocardial infarction in real-world clinical practice, and describe their patient characteristics and duration of treatment. If the a priori threshold of 5,000 person-years on treatment with ticagrelor 60 mg is met, outcome events (bleeding and cardiovascular events) will also be analysed and described.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction (MI)

Detailed Description

This observational cohort study will include patients initiating treatment with ticagrelor 60 mg after a myocardial infarction (MI), and describe their patient characteristics and persistence to treatment. To contextualise the characteristics of the ticagrelor patients, two reference cohorts will be created, including patients treated with another P2Y12 inhibitor than ticagrelor (clopidogrel, prasugrel, or ticlopidine), and patients not treated with any P2Y12 inhibitor, within a comparable timepoint from an MI as for the ticagrelor 60 mg patients. If the a priori threshold of 5,000 person-years on treatment with ticagrelor 60 mg is met, to ensure sufficient precision, outcome events (bleeding and cardiovascular events) will also be analysed and described. Outcome events will only be described in the ticagrelor cohorts; no comparison of outcomes will be made between the ticagrelor and the reference cohorts.

The primary outcome is bleeding requiring hospitalisation. The secondary outcomes include components of the primary outcome, and cardiovascular outcomes. Persistence to treatment with ticagrelor 60 mg will also be assessed The study will be performed in the US and 4 European countries (Sweden, United Kingdom, Italy, Germany).

• Study Type: Observational
• Enrollment (Actual): 7035

Contacts and Locations

Study Locations

• Germany
  • Wismar, Germany
    • Research Site
• Italy
  • Rome, Italy
    • Research Site
• Sweden
  • Stockholm, Sweden
    • Research Site
• United Kingdom
  • London, United Kingdom
    • Research Site
• United States
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • Research Site
  • Massachusetts
    • Waltham, Massachusetts, United States, 02451
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 130 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This study will include patients who are hospitalised with a primary diagnosis of MI, identified using diagnostic codes, divided into cohorts receiving and not receiving treatment with ticagrelor 60 mg. Co-prescription of aspirin will also be identified where available.

Description

Inclusion Criteria:

Primary Analysis Population:

• Hospitalisation with a primary diagnosis of MI during the eligibility period
• Ticagrelor cohort: A first prescription of ticagrelor 60 mg after the most recent hospitalisation with a primary diagnosis of MI.
• Non-ticagrelor cohort: A prescription of clopidogrel, prasugrel or ticlopidine, or no prescription for any of these medications, at a comparable timepoint relative to their MI as for the ticagrelor cohort

Secondary Analysis Population:

• The qualifying prescription 12-36 months after a hospitalisation with a primary diagnosis of MI and treatment with an ADP receptor antagonist (clopidogrel, prasugrel, ticagrelor 90 mg, ticlopidine) ≤12 months prior to the qualifying prescription, or the qualifying prescription 12-24 months after a hospitalisation with a primary diagnosis of MI AND
• Age ≥50 years

• At least one of the following risk factors:

  • Age ≥ 65 years
  • Diabetes mellitus requiring medication
  • A second prior MI
  • Evidence of multivessel coronary artery disease
  • Chronic non-end-stage renal dysfunction

Exclusion Criteria:

Applicable to the Primary and Seconday Analysis Populations:

• Dies, emigrates, or disenrolls from the database (where applicable) prior to the ticagrelor approval date.

• Ineligibility for ticagrelor use (restricted to the conditions possible to capture within the data sources)-one or more of the following:

  • Concomitant use of an anticoagulant
  • Prior ischaemic stroke
  • Prior history of intracranial bleeding
  • Severe hepatic impairment
  • Gastrointestinal bleeding
  • Renal failure requiring dialysis
  • Concomitant use of a strong CYP3A4 inhibitor or inducer
• <1 year of data available prior to the qualifying MI (for assessment of patient characteristics at qualifying MI)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Ticagrelor cohort; Patients initiating ticagrelor 60 mg after an MI, with no prescription of ticagrelor 60 mg prior to their qualifying MI. The qualifying MI is defined as the most recent MI occurring before the first ticagrelor 60 mg prescription.
Non-ticagrelor cohort; Patients not prescribed ticagrelor 60 mg at a comparable time point after an MI as matched patients in the ticagrelor cohort. Patients may be prescribed another P2Y12 inhibitor or aspirin alone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment persistence	Treatment discontinuation is defined on the basis of calculated days of supply from prescription data.	From initiation of ticagrelor 60 mg to discontinuation, switch or death, assessed throughout the study period up to a maximum of 36 months
Incidence of Major bleeding	Major bleeding is defined as bleeding requiring hospitalisation.	From initiation of ticagrelor 60 mg until the date of a major bleeding event, assessed throughout the study period until treatment discontinuation or end of follow-up, up to a maximum of 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Bleeding events	Intracranial haemorrhage; Gastrointestinal bleeding requiring hospitalisation; Bleeding other than intracranial haemorrhage or gastrointestinal bleeding requiring hospitalisation; Fatal bleeding; Bleeding not requiring hospitalisation (managed in outpatient care/emergency care not requiring hospitalisation)	From initiation of ticagrelor 60 mg until the date of a bleeding event, assessed throughout the study period until treatment discontinuation or end of follow-up, up to a maximum of 36 months
Incidence of Cardiovascular (CV) events	Composite of hospitalisation for MI or stroke, and all-cause mortality; Composite of hospitalisation for MI or stroke, and CV death (three-point MACE); Hospitalisation for MI, hospitalisation for stroke, hospitalisation for ischaemic stroke, CV death, CHD death, all-cause mortality assessed individually	From initiation of ticagrelor 60 mg until the date of a CV event, assessed throughout the study period until treatment discontinuation or end of follow-up, up to a maximum of 36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dyspnoea	Dyspnoea is assessed as dyspnoea diagnosed in any setting, as well as dyspnoea requiring hospitalisation, where data availability allows.	From initiation of ticagrelor 60 mg until the date of a dyspnoea event, assessed throughout the study period until treatment discontinuation or end of follow-up, up to a maximum of 36 months
Incidence of Amputation (lower-limb)	Amputation (lower-limb) is defined as hospitalisation with a procedure code for amputation of lower limb.	From initiation of ticagrelor 60 mg until the date of amputation of lower limb, assessed throughout the study period until treatment discontinuation or end of follow-up, up to a maximum of 36 months

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2020
• Primary Completion (Actual): June 28, 2021
• Study Completion (Actual): June 28, 2021

Study Registration Dates

• First Submitted: September 15, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (Actual): September 29, 2020

Study Record Updates

• Last Update Posted (Actual): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Cohort study; Cardiovascular; Bleeding; Myocardial Infarction; Observational study; Drug utilization; MACE; Antiplatelet agents; Real-world evidence; Ticagrelor 60 mg; Medication persistence
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction
• Other Study ID Numbers: D5130R00057

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No