Clinical trial NCT06637657: Guided Optimisation of Long-term Disease rEduction in secoNdary Prevention of CVD
Official title: Guided Optimisation of Long-term Disease rEduction in secoNdary Prevention of CVD (GOLDEN). A Prospective Observational Study of Long-term Outcomes.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Acute Coronary Syndrome
Keywords: Cardiovascular prevention
Coronary revascularisation
Pharmacological approach
Teachable moment
Major cardiovascular events
Acute Coronary Syndrome
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Dutch Network for Cardiovascular Research (WCN), Utrecht
name: Novartis Pharmaceuticals
name: Amarin Pharma Inc.
First posted: 2024-10-15
Enrollment: 5586
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population will consist of all patients who have consented to the use of their clinical data and who are hospitalized at cardiology departments of participating hospitals (Dutch Network for Cardiovascular Research (WCN and University Medical Centers) in the Netherlands.

Brief summary: The goal of this observational study is to evaluate the implementation of a 'first-time-right' pharmacological treatment strategy in patients hospitalized with coronary artery disease.

The main question it aims to answer is:

Does early (immediately post-event) initiation of a full set of guideline-based, individualized, preventive medication lead to reductions in cardiovascular events compared to current practice (incremental titration strategies)?

Researchers will compare the 'first-time-right' strategy group to the current practice group to see if there are improvements in major adverse cardiac and cerebrovascular events (MACE) at 36 months.

Participants will:

* Receive either the 'first-time-right' strategy or current practice for secondary prevention.
* Be monitored (data collection) through routine clinical visits at baseline, 8 weeks, 12, and additional telephone contacts at 24, and 36 months after discharge.
* Complete online questionnaires at hospitalization, 8 weeks, 12, 24, and 36 months after discharge.

Detailed description: Rationale:

Individuals with clinically established coronary artery disease are at high risk of recurrent events and death. To reduce this risk, incremental titration of preventive medication to reach pre-defined risk factor targets is recommended by international guidelines.

However, using this approach, disappointing reductions in risk are generally attained, mainly resulting from inadequate use of preventive medication. The European 2021 Prevention guidelines recommend compressing preventive strategies into a maximum of two steps: first, attainment of 'minimal' risk-factor targets, followed by rapid individualized residual risk management (1). While the conventional interpretation of preventive guidelines has led to medication titration over months or even years, - with suboptimal results, the new guideline-based approach de facto constitutes a front-loaded, 'first- time-right' strategy, where as early as during hospitalization, a complete medication plan is formulated and implemented. However, the practical implementation and effects on clinical outcomes of such a strategy have not been investigated. The investigators therefore aim to investigate the effects of implementing a 'first-time-right' guideline-based pharmacological treatment strategy, compared to current incremental, individual-titration strategies, in patients hospitalized with coronary artery disease. As both treatment strategies constitute a different application of current international guidelines, no experimental treatments are included. The investigators will therefore conduct an observational study to investigate the effects of both strategies. The investigators hypothesize that application of the first-time-right pharmacological strategy, i.e. early (immediately post-event) initiation of a full set of guideline-based, individualized, preventive medications will lead to greater risk factor control, and to reductions in cardiovascular events, compared to current practice (i.e. incremental titration strategies).

Goals:

Primary Objective: To evaluate the impact of a 'first-time-right' pharmacological risk factor management strategy, according to the European 2021 Prevention guidelines, compared with current practice (i.e. incremental titration) on major adverse cardiac- and cerebrovascular events (MACE, 4-point: CVD death, myocardial infarction, (ischemic or hemorrhagic) stroke, and ischemia-driven revascularization) at 36 months. Secondary objectives: CVD death, myocardial infarction, stroke, and ischemia-driven revascularization (plus in 2 and 3-point MACE combinations), acute limb ischemia, carotid revascularization, unplanned cardiovascular hospital readmission, improvement in cardiovascular risk factors (drug- targeted and lifestyle-related risk factors), self-reported medication use and adherence scores, quality of life.

Study design:

GOLDEN is a prospective, observational study designed to evaluate the implementation of the guideline-based 'first-time-right' strategy in at least 30 cardiology departments in the Netherlands (Figure 1, Appendix). Study supervision, including data management and statistical analyses of the study, will be performed and coordinated at the Amsterdam UMC, assisted by the Dutch Network forCardiovascular Research (WCN), Utrecht, The Netherlands.

The study will be embedded in the collaboration of the partners of the Dutch Cardiovascular Alliance, supporting the goal of reducing the cardiovascular disease burden in The Netherlands by collaboration in research and implementation. Amsterdam UMC has the role of sponsor and is responsible for the scientific and operational leadership. When all relevant national partners support the implementation goal of First Time Right, participating centers will be recruited within the academic centers (through NetherLands Heart Institute, NLHI) and non-academic centers (through the Dutch Network for Cardiovascular Research, WCN), Utrecht, The Netherlands. Patient data will be captured and stored in an electronic database (Castor) and will only be available for the investigator (sponsor). WCN (Werkgroep Cardiologische centra Nederland) is a research network of cardiovascular investigators (www.WCN.life). The network consists of nearly 60 cardiovascular research departments across the Netherlands. The WCN office provides central support to both the sponsor and the participating sites through central feasibility, site ID, contracting, recruitment and quality support. The research professionals are employed by each individual site. Data on patient inclusion and data quality will be shared with WCN for quality assurance purposes. No individual patient data will be shared with WCN.

Our observational study comprises two groups:1) The 'current practice' group, constituting current secondary prevention practices treated patients (i.e. incremental, individual titration at treating physician's discretion) 2) The 'first-time-right' group, when the 'first- time-right' guideline-based strategy is implemented. The study program is outlined in Figure 2 (Appendix). All centers will start including in the 'current practice' arm. After inclusion of 50% of the sample size, a blanking period of 8 weeks will be observed, where no inclusions will take place in any center. This time period will be used to train all participating centers in the 'first-time-right' strategy.

Subsequently, all centers will proceed to include in the 'first-time- right' cohort. The 'current practice' treated patients' group will provide data on current practices in the preventive treatment after hospitalization for acute coronary syndrome or coronary revascularization.

Eligibility criteria: Inclusion Criteria:

* \>18 years of age (no upper limit)
* Coronary event, i.e. ACS or coronary revascularisation
* Able to provide informed consent

Exclusion Criteria:

* (short-term planned) pregnancy or breast feeding
* Dialysis

Primary outcomes:
measure: 4-point MACE
timeFrame: 36 months
Secondary outcomes:
measure: Uncombined MACE evaluations
timeFrame: 8 weeks, 12 months, 24 months, 36 months after discharge
measure: Combined outcomes: 2-point and 3-point MACE
timeFrame: 8 weeks, 12 months, 24 months, 36 months after discharge
measure: Extended MACE
timeFrame: 8 weeks, 12 months, 24 months, 36 months after discharge
measure: Unplanned cardiovascular hospital readmission
timeFrame: 8 weeks, 12 months, 24 months, 36 months after discharge
measure: LDL-cholesterol
timeFrame: baseline= (max. 3 months) prior to event or revascularisation procedure, 8 weeks, 12 months after discharge
measure: Diastolic blood pressure
timeFrame: baseline= (max. 3 months) prior to event or revascularisation procedure, 8 weeks, 12 months after discharge
measure: C-reactive protein
timeFrame: baseline= (max. 3 months) prior to event or revascularisation procedure, 8 weeks, 12 months after discharge
measure: Fasting glucose
timeFrame: baseline= (max. 3 months) prior to event or revascularisation procedure, 8 weeks, 12 months after discharge
measure: HbA1c
timeFrame: baseline= (max. 3 months) prior to event or revascularisation procedure, 8 weeks, 12 months after discharge
measure: Systolic blood pressure
timeFrame: baseline= (max. 3 months) prior to event or revascularisation procedure, 8 weeks, 12 months after discharge
measure: Medication Adherence Report Scale (MARS5)
timeFrame: baseline= between event or coronary intervention and discharge, 8 weeks, 12 months, 24 months, 36 months
measure: visual analog scale (VAS) medication adherence
timeFrame: baseline= between event or coronary intervention and discharge, 8 weeks, 8 weeks, 12 months, 24 months, 36 months
measure: Beliefs about Medicine (BMQ)
timeFrame: baseline= between event or coronary intervention and discharge, 8 weeks, 8 weeks, 12 months, 24 months, 36 months
measure: Quality-of-Life (QoL)
timeFrame: baseline= between event or coronary intervention and discharge, 8 weeks, 8 weeks, 12 months, 24 months, 36 months
Other outcomes:
measure: The iMTA Medical Consumption Questionnaire (iMCQ)
timeFrame: baseline= between event or coronary intervention and discharge, 8 weeks, 12 months, 36 months
measure: The iMTA Productivity Cost Questionnaire
timeFrame: baseline= between event or coronary intervention and discharge, 8 weeks, 12 months, 36 months
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
Study officials:
affiliation: Amsterdam UMC
name: Marjolein Snaterse, dr.
role: STUDY_CHAIR
affiliation: Amsterdam UMC
name: Fabrice M.A.C. Martens, Prof. dr.
role: STUDY_CHAIR
affiliation: Amsterdam UMC
name: Harald T. Jorstad, dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Back M, Benetos A, Biffi A, Boavida JM, Capodanno D, Cosyns B, Crawford C, Davos CH, Desormais I, Angelantonio ED, Franco OH, Halvorsen S, Richard Hobbs FD, Hollander M, Jankowska EA, Michal M, Sacco S, Sattar N, Tokgozoglu L, Tonstad S, Tsioufis KP, van Dis I, van Gelder IC, Wanner C, Williams B; ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies With the special contribution of the European Association of Preventive Cardiology (EAPC). Rev Esp Cardiol (Engl Ed). 2022 May;75(5):429. doi: 10.1016/j.rec.2022.04.003. No abstract available. English, Spanish.