Evaluating risk stratification tools that assess the risk of bleeding whilst using antiplatelet therapy following myocardial infarction.

Liverpool University Hospitals NHS Foundation Trust (LUH NHS FT) requires access to NHS England data for the purpose of the following research project:

Comparison of ticagrelor with clopidogrel in a real-world population of patients treated for acute coronary syndrome.

The following is a summary of the aims of the research project provided by LUH NHS FT:

Following myocardial infarction (MI (heart attack)), patients are typically placed on medication that thin the blood by reducing platelet activity (anti-platelets). This is usually aspirin and another agent, e.g., clopidogrel or ticagrelor. However, these medications risk causing bleeding; this bleeding can be life-threatening or leave the patient with significant long-term health effects. Therefore, a balance needs to be struck between preventing subsequent MIs and the risk of bleeding when using these medications. Striking this balance is complex and often done poorly. As a result, tools to help calculate the risk have been created. Unfortunately, there is uncertainty around the validity of these scores; therefore, they are often underutilised.

This study aims to assess the validity of these bleeding metrics within a cohort of patients and highlight the best-performing tool. In doing so, LUHNHS FT hope that providing clinicians with the confidence to use these tools will optimise antiplatelet prescription, reducing the occurrence of major bleeding and subsequent MIs.

The following NHS England Data will be accessed:

> Hospital Episode Statistics Admitted Patient Care (HES APC) – necessary to obtain data on episodes of bleeding prior to the event date, but also data on whether cohort members have been diagnosed with cirrhosis, thrombocytopenia, a clotting disorder, cancer or have had recent surgery or trauma. This information will allow LUH NHS FT to capture important comorbidities that form part of the risk scores bleeding.

The level of the Data will be identifiable.

The Data will be minimised as follows:

> Limited to a study cohort identified by LUH NHS FT – utilising an existing database of 5,250 patients recruited in the Merseyside region, curated for the ROBOT-ACS study. The inclusion criteria, exclusion criteria and duration of follow-up for the database was as follows:

Inclusion Criteria

1. Patient commenced on clopidogrel or ticagrelor for acute coronary syndrome (ACS).

Exclusion Criteria

1. Patient already taking the drug in question (clopidogrel or ticagrelor) prior to the ACS event.

2. Patients under 18 years of age.

3. Patients in whom the drug is stopped during the same hospital admission due to clinical judgement dictating that it is no longer indicated (this does not apply to patients in whom a bleeding event is the precipitant for stopping the drug).

> Limited to data between 2007/08 and 2024/25

> 3 years prior to the date of enrolment for each participant will be supplied (data will be filtered from this date to 2024/25 data)

LUH NHS FT is the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above.

The lawful basis for processing personal data under the UK GDPR is: Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller.

The lawful basis for processing special category data under the UK GDPR is: Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

This process is in the public interest as it aligns with the UK Policy Framework for Health and Social Care, which protects and promotes the interests of patients, service users, and the public. It also aims to generate data to validate metrics used in assessing bleeding risk in patients.

The funding is provided by Menarini. The funding is specifically for the study described.

The funder(s) will have no ability to suppress or otherwise limit the publication of findings.

Data will be accessed by substantive employees of LUH NHS FT.

Menarini work in area of anti-platelet therapy, Menarini are assisting with costs associated with the data request. They have no direct involvement or product interest in the research study.

LUH NHS FT will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number, Date of Birth,Gender and Study ID) for the cohort to be linked with NHS England data.

NHS England will provide the relevant records from the HES APC to LUH NHS FT. The Data will

> contain no direct identifying data items but will contain a unique person ID which can be used to link the Data with other record level data already held by the recipient

The Data will not be transferred to any other location.

The Data will be stored on servers at LUH NHS FT

The data will be processed by substantive employees of LUH NHS FT

The Data will be accessed by authorised personnel via remote access.

The Controller(s) must confirm and provide evidence upon audit by NHS England that access via any remote device complies with the data security obligations within this DSA and the Data Sharing Framework Contract.

For remote access:

- Remote access will only be from secure locations situated within the territory of use (as further restricted elsewhere within the DSA if so done) stated within this DSA;

- Access controls granting users the minimum level of access required are in place;

- Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data;

- Multifactor authentication (MFA) is required for remote access;

- Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access;

- All remote access is undertaken within the scope of the organisation’s DSPT (or other security arrangements as per this DSA) and complies with the organisation’s remote access policy.

The above applies in addition to any condition set out elsewhere within the DSA (e.g. who may carry out processing, and for what purpose).

Remote processing will be from secure locations within England. The data will not leave England at any time.

All personnel accessing the Data have been appropriately trained in data protection and confidentiality.

There will be no requirement and no attempt to re-identify individuals when using the Data.

Researchers from the LUH NHS FT will analyse the Data for the purposes described above.

The expected outputs from this data access request include the following:

- Dictate local prescribing practice in Merseyside and influence what bleeding scores are used locally to determine treatment of patients with high bleeding risk.

- Publish work in peer reviewed journals in the year following receipt of the data. Allowing this work to be viewed internationally and guide prescribing post myocardial infarction, for those with high bleeding risk.

- Presentation a local, regional and potentially national meetings and conferences.

Major bleeding post-myocardial infarction portends poor outcomes. Moreover, it is often unclear for clinicians the degree to which particular risk factors such as renal dysfunction, advanced age, or frailty contribute to the bleeding risk. Amidst this uncertainty, the utility of scoring systems like CRUSADE, precise-DAPT, ACUITY, and ARC-HBR becomes paramount in guiding clinical decision-making to mitigate bleeding risks while optimizing therapeutic interventions for myocardial infarction patients.

Models are typically based on select patient populations (often those who are percutaneous coronary intervention and surgical candidates). Given that we have a broad selection criterion with and minimal exclusion criteria, we feel our population reflects the UK patient population more accurately. We therefore feel well placed to test the external validity of these metrics.

Ensuring the validity of scoring systems like CRUSADE, precise-DAPT, ACUITY, and ARC-HBR in real-world populations is essential for their safe, effective, and confident application in clinical practice. We believe that the use of validated models allows the judicious prescription of antiplatelet medication, leading to less subsequent cardiac mobility and mortality, whilst also reducing incidence of major bleeding. Conversely removal of models with poor external validity, we believe, will hold similar benefit.

The findings of our study will be published in a medical journal for clinicians and policy makers to read. Informing the use of bleeding metrics in clinical practice and future guidelines. We also aim to disseminate our findings at a conference, for cardiology specialists.

It is expected that the results of this research will have an immediate and lasting impact, as the prescription of antiplatelet medication will almost indefinitely continue for the foreseeable future.

The above-named bleeding risk tools are used internationally. Therefore, LUH NHS FT hope the reach of their research will be international too. Considering myocardial infarction is a common hospital presentation, the proposed benefits are expected be relevant to a large number of patients and LUH NHS FT believe that this will improve patients' quality of care in the UK and beyond.

Yielded Benefits is not a requirement for new applications.