Clinical trial NCT05844566: OptimiZation Of Lipid Lowering Therapies Using a Decision Support System In Patients With Acute Coronary Syndrome.
Official title: Implementation of a Decision Support System and Its Effect on Early Optimisation of Lipid-Lowering Therapies in Patients With Acute Coronary Syndrome: a Cluster Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Coronary Syndrome
Myocardial Infarction
Keywords: Acute Coronary Syndrome
Decision Support System
Lipid Lowering Therapies
Low Density Lipoprotein
Heart Attack
ST Elevation Myocardial Infarction
Non-ST Elevation Myocardial Infarction
Coronary Disease
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Sanofi
name: Axtria, Inc.
name: Hospital Universitario La Paz
name: Hippocrates Research
First posted: 2023-05-06
Enrollment: 1139
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Cluster randomised controlled trial. Study sites are randomised to intervention or no intervention.
Primary purpose: OTHER

Brief summary: The goal of this clinical trial is to compare implementation of a Decision Support System (DSS) - aligned to the 2019 ESC/EAS Guidelines - in addition to routine clinical care versus routine clinical care without availability of a DSS, in participants aged ≥18 to \< 80 years old presenting with Acute Coronary Syndrome (ACS).

The main questions it aims to answer are:

* to assess whether the availability of a DSS (which provides estimates of risk and estimates of potential benefit through LDL-C lowering) to current practice results in an increase in the early initiation of combination Lipid Lowering Therapies (LLTs) or intensification of LLT regimens compared to current practice alone over a 16-week period after an Acute Coronary Syndromes (ACS) event
* To estimate in the study cohort the potential benefits of guideline-based LLT intensification via simulation-based methods using estimates of baseline risk: LLT utilisation, additional LDL-C reductions and LDL-C goal achievement, on simulated risk of CV events through modelling.

Participants will give consent to randomised clinical sites to collect their data. The clinical sites will either be randomised to standard of care or the availability of and access to the DSS.

Researchers will compare patients from DSS and Non-DSS sites to see if the availability of the DSS results in implementation of more intensive lipid lowering regimens, resulting in the achievement of lower LDL-C values as well as the proportion of patients who reach target LDL-C levels (\<1.4 mmol/L (\<55 mg/dL) by Week 16.

Detailed description: Patients with acute coronary syndromes (ACS) including myocardial infarction (MI) remain at risk of future cardiovascular events depending upon the interaction between inherited genetic factors/ and environmental factors including cholesterol over their lifetime. Expert guidelines on secondary prevention such as the ESC therefore increasingly recognise a more individualised approach.

Lowering LDL-C with high intensity lipid lowering therapies (LLTs) initiated within 10 days of an ACS reduces risk more than less intense regimens. In the SWEDEHEART registry which included 40,6007 patients over a median follow up of 3.78 years, patients who achieved the largest absolute reductions in LDL-C or greatest percentage reduction in LDL-C, had the lowest risk of a range of cardiovascular events and mortality. The approach to use of lipid lowering (LLT) was statin based monotherapy with few attaining the recommended cholesterol goals.

The 2019 European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) dyslipidaemia guidelines categorise patients with an ACS event as very-high risk and recommend an LDL-C goal of \< 1.4 mmol/L (\<55 mg/dL) and \>50% reduction in LDL-C in this population. But several studies in European populations have highlighted gaps between clinical practice/ implementation of treatment recommendations compared with evidence based guideline recommendations. In the DA VINCI study representing 5,888 patients prescribed LLT in 18 European countries, LDL-C goal achievement in very-high risk populations was just 39% per 2016 ESC/EAS guidelines of\<1.8mmol/L with only about 18% achieving the new recommended lower goal of \<1.4mmol/L. It has become clear that greater implementation/ use of available combination therapies will be needed if lower recommended goals are to be achieved. It is unclear what the barriers are to earlier implementation and may include a lack of physician understanding of risk of further CV events or a lack of understanding of the quantifiable benefits from specific magnitudes of LDL-C lowering.

The aim of this trial is to assess whether providing information to those managing ACS patients that quantify absolute risk and the absolute benefit from different lipid lowering regimens through access to a Decision Support Tool (DSS) system is more likely to result in earlier intensification of lipid lowering regimens and thus result in a greater proportion of patients achieving the ESC lipid lowering goals after ACS compared to patients being managed routinely without access to a DSS standard (cluster RCT design). It is well established that unless treatments are initiated through secondary care or as part of acute care pathways, there is considerable inertia in further optimisation of treatment in primary care. Thus, this trial will assess whether presenting quantifiable data on risks and benefits results in behaviour change among secondary care physicians and improves cholesterol management within 4 months of an ACS.

The DSS is available online or remotely accessible via a website intended for clinicians to estimate the clinical benefit of any LLT regimen, whether single or combination therapies. The DSS shows the expected risk, risk reductions and number needed to treat for the various treatments selected by the clinical user on the potential value of initiation of an add-on therapy for reducing the risk of other Cardiovascular (CV) events. This DSS provides a graphical and tabular representation of the time-dependent CV treatment benefit model for LLTs published in a peer-reviewed journal article.

The trial hypothesises that having a pictorial representation of both individual risk and recommended treatments will encourage clinicians to implement clinical guidelines more closely. The clinicians using the DSS will be asked to complete a DSS evaluation at the end of the trial. Implementing the patient-specific recommendation remains at the clinicians' discretion.

Eligibility criteria: Inclusion criteria:

Sites:

* Manage ACS patients as defined by: Symptoms of myocardial ischemia with an unstable pattern, occurring at rest or with minimal exertion, within 72 hours of an unscheduled hospital admission due to presumed or proven obstructive coronary disease and at least one of the following:

  * Elevated cardiac biomarkers
  * Resting electrocardiographic changes consistent with ischemia or infarction, plus additional evidence of obstructive coronary disease from regional wall motion or perfusion abnormality, 70% or more epicardial coronary stenosis by angiography, or need for coronary revascularization procedure
* Mange post ACS follow up care of patients including risk factor control
* Ability to provide follow up information on patient care for a minimum of 16 weeks including blood tests
* Willing/ able to access and undertake training for the DSS
* Adequate internet connection at site and the ability to access the DSS
* No restrictions on use of LLTs (within national guidelines/ reimbursement)
* Ability to include all essential parameters and patient information for DSS input

Participants:

* Aged ≥18 to \< 80 years old
* Provide written informed consent
* Presenting to a study site with ACS as LLT naïve, monotherapy or combination therapy (defined as more than one LLT agent)
* Willing to take lipid lowering treatments for the secondary prevention of cardiovascular disease
* Attending the same study site (or same clinical team) for ACS follow up to ensure follow up data can be collected; or ensure that follow up data can be collected from other clinical institutions as part of the clinical pathway.

Exclusion criteria:

Sites:

* Unable to capture/ provide data on patients with ACS during admission and follow up
* Unable or unwilling to use lipid lowering treatments other than statins for ACS care

Participants:

* Unable to provide written informed consent
* LDL-C measurement \< 1.8 mmol/L at admission

Primary outcomes:
measure: Optimisation of the intensity of Lipid Lowering Therapy within 16 weeks of index ACS
timeFrame: 16 weeks
Secondary outcomes:
measure: Time to initiation
timeFrame: 16 weeks
measure: LDL-C Level
timeFrame: 16 weeks
measure: Target LDL-C reduction
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: AUSL di Bologna-Ospedale Maggiore
city: Caserta
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale (A.O.R.N.) "Sant'Anna e San Sebastiano" di Caserta
city: Foggia
country: Italy
facility: A.O.U. Ospedali Riuniti U.O.C. Cardiologia e UTIC
city: Genova
country: Italy
facility: IRCCS. A.O.U. Policlinico San Martino IST
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Gaetano Martino
city: Milan
country: Italy
facility: IRCCS Policlinico San Donato
city: Modena
country: Italy
facility: A.O.U Policlinico di Modena S.C. di Cardiologia
city: Pisa
country: Italy
facility: Ospedale di Cisanello - A.U.O.P. Azienda Ospedaliera Universitaria
city: Reggio Emilia
country: Italy
facility: AUSL-IRCCS di Reggio Emilia
city: Roma
country: Italy
facility: Ospedale Sandro Pertini - ASL Roma 2
city: Udine
country: Italy
facility: Azienda Ospedaliero Universitaria Santa Maria della Misericordia
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario Santiago de Compostela
state: A Coruña
city: A Coruña
country: Spain
facility: University Hospital of A Coruña
state: Coruña
city: Boadilla del Monte
country: Spain
facility: Hospital HM Montepríncipe
state: Madrid
city: Majadahona
country: Spain
facility: Puerta de Hierro Majadahonda University Hospital
state: Madrid
city: Móstoles
country: Spain
facility: Hospital Universitario Rey Juan Carlos
state: Madrid
city: El Palmar
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
state: Murcia
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario La Luz Quiron
city: Madrid
country: Spain
facility: Gregorio Marañón General University Hospital
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Seville
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Luton
country: United Kingdom
facility: Luton and Dunstable University Hospital
state: Bedfordshire
city: Bodelwyddan
country: United Kingdom
facility: Glan Glwyd Hospital
state: Denbighshire
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: Dorset
city: Brighton
country: United Kingdom
facility: Conquest Hospital
state: East Sussex
city: Scunthorpe
country: United Kingdom
facility: Scunthorpe General Hospital
state: North Lincolnshire
city: Kettering
country: United Kingdom
facility: Kettering General Hospital
state: Northamptonshire
city: Portadown
country: United Kingdom
facility: Southern Health and Social Care Trust, Craigavon Area Hospital
state: Northen Ireland
city: Bath
country: United Kingdom
facility: Royal United Hospital
state: Somerset
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
state: Tyne And Wear
city: North Shields
country: United Kingdom
facility: North Tyneside General Hospital
state: Tyne And Wear
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
state: Tyne And Wear
city: Birmingham
country: United Kingdom
facility: Sandwell General Hospital
state: West Midlands
city: Dudley
country: United Kingdom
facility: Russell's Hall Hospital
state: West Midlands
city: Worthing
country: United Kingdom
facility: Worthing Hospital
state: West Sussex
city: Halifax
country: United Kingdom
facility: Calderdale Royal Hospital
state: West Yorkshire
city: Worcester
country: United Kingdom
facility: Worcestershire Royal Hospital
state: Worcestershire
city: London
country: United Kingdom
facility: Hammersmith Hospital
Study officials:
affiliation: Imperial College London
name: Kausik Ray, Professor
role: PRINCIPAL_INVESTIGATOR
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