The ZON-HR is a prospective multicentre registry of all consecutive patients with coronary artery disease at 4 participating PCI centres and 3 referral centres in the southeastern region of the Netherlands who undergo clinically indicated PCI at one of the following participating centres: Radboud university medical centre, Maastricht University Medical Centre, Zuyderland Medical Centre and VieCuri Medical Centre. Annually, approximately 3500 patients undergo PCI at one of these participating centres, of whom two-thirds have ACS. Of all the patients in the ZON-HR, 20% come from referral centres.

Data collection started in November 2020 (at the first centre) and is ongoing. Data are collected in Castor Electronic Data Capture (EDC) [17] in a pseudonymised manner. This registry was evaluated by the medical ethics committee Zuyderland & Zuyd. As patients are not subjected to any procedures other than those recommended in the guidelines and protocols and because the main purpose of this registry is quality control, the registry is not subject to the Dutch Medical Research Involving Human Subjects Act (Wet medisch-wetenschappelijk onderzoek met mensen). Therefore, no informed consent is required. However, patients are offered an opt-out option via follow-up questionnaires. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and is registered at ClinicalTrials.gov (NCT06512493).

All patients undergoing PCI are included in the registry. In line with the NHR, failed PCI attempts are considered as a performed PCI as long as a coronary wire has been inserted in the target vessel. Patients undergoing multiple PCIs are considered as a ‘new’ patient when the consecutive PCI is performed > 1 year after the index PCI. This is based on the follow-up duration of 1 year in the majority of patients and is in line with the NHR, in which a new 1‑year follow-up period is started for patients who present > 1 year after the initial PCI. Only in patients who are regarded to be at long-term high ischaemic risk based on their presentation and patient characteristics (Fig. 1), 2‑year follow-up data are collected. For all individual analyses, it will be determined and subsequently described whether a correction is required for patients who are included more than once in the registry.

Protocols for personalised dual antiplatelet therapy in patients undergoing (PCI), for those a without concomitant oral anticoagulant (OAC) treatment and b with concomitant OAC treatment. ACS acute coronary syndrome, BARC Bleeding Academic Research Consortium, eGFR estimated glomerular filtration rate, Hb haemoglobin, CTO chronic total occlusion, ASA acetylsalicylic acid

All interim PCIs are regarded as follow-up to the index PCI. No in- or exclusion criteria are applied to achieve 100% registration in order to prevent bias. Therefore, the registry data can be regarded as real-world data.

The interventional procedures and concomitant pharmaceutical treatment are performed in accordance with the ESC Guidelines for CCS and ACS [9, 10]. To stimulate personalised secondary prevention post-PCI in accordance with the guidelines, the ZON-HR promotes the use of risk stratification after PCI to determine bleeding and ischaemic risks and guide antiplatelet strategy. To increase the feasibility of risk stratification, the ZON-HR Consortium has developed a simplified protocol for the antiplatelet strategy based on patient and procedural risk factors and the use of oral anticoagulants (Fig. 1). In this protocol, the criteria for bleeding and ischaemic risks are derived from the ESC Guidelines and are based on validated risk scores [2, 4, 8] and consensus documents, such as the criteria from the Academic Research Consortium for High Bleeding Risk [18]. The ZON-HR selected criteria for bleeding and ischaemic risks and excluded rare diseases or criteria commonly unknown at the time of the procedure. This protocol has been implemented at all participating centres where interventional cardiologists document the proposed antiplatelet strategy directly after PCI. The simplified protocol for bleeding risk has yet been externally validated and has shown a good prognostic value [19].

These criteria can be built into the electronic health record (EHR) and then generate an automated advice on antiplatelet duration according to the ZON-HR protocol. The interventional cardiologist can choose to follow or deviate from this advice according to the clinical setting.

To further enhance personalised treatment, the ZON-HR promotes active screening for de novo or undertreated DM by measuring HbA1C values in patients admitted with ACS since 2022. In addition, monitoring of cholesterol management during out-patient visits is stimulated, specifically in ACS patients.

In addition to the NHR data, the ZON-HR collects additional risk factors at baseline for ischaemic and bleeding risks and data regarding procedural characteristics and periprocedural complications. Furthermore, follow-up data have been expanded by the addition of bleeding and ischaemic events and medication use. A full list of parameters included in this registry is presented in Table S1 (baseline characteristics) and Table S2 (follow-up characteristics) in the Electronic Supplementary Material. The definitions of these parameters are explained in the tables unless they have been previously described by the NHR [20, 21].

At baseline, prespecified demographics, laboratory values and procedural characteristics (see Table S1 in Electronic Supplementary Material) that are available in the EHR are derived from the EHR and imported into Castor EDC. Additionally, medication at discharge standardly prescribed after a PCI or an ACS is collected in Castor EDC (see Table S1 in Electronic Supplementary Material). Discharge medication from referral centres is collected by digital questionnaires that are sent 1 week after discharge. Data regarding medical history, risk factors, complications during PCI and advice on the duration of dual antiplatelet therapy (DAPT) are registered by the interventional cardiologist that performed the PCI. These parameters are collected either directly in Castor EDC or in the EHR, from which they are exported and then imported into Castor EDC.

Outcomes including complications after 1 month, 1 year and 2 years post-PCI (see Table S2 in Electronic Supplementary Material) are collected using digital questionnaires. Patient-reported outcomes are verified by EHR research and thereafter registered in the ZON-HR database.

Frequent monitoring of survey progression is done by researchers once per 1–2 weeks. If a patient fails to fill in the questionnaire, a reminder is sent. In case of no digital response, the patient is contacted by telephone in order to complete the follow-up. If this is not possible, the follow-up from non-responders is manually searched in the EHRs. This is required in approximately 60% of the patients. If these patients have their follow-up visits outside of the participating centres, they are regarded as lost to follow-up. Follow-up data collected by the NHR are matched with the data collected as described above in order to ensure completeness and consistency between the NHR and ZON-HR, which is of special importance for the follow-up of patients who do not receive follow-up treatment at one of the participating ZON-HR centres.

Laboratory results including LDL‑C and HbA1c values are collected from the EHR at 2 time points after PCI: at around 30 days and 365 days post-PCI. These questionnaires offer an opt-out option for the use of data for quality or research purposes. Approximately 3.5% of the patients who respond to the questionnaires choose the opt-out for the use of their data. In case of mortality, it is registered whether the cause of death was cardiovascular or non-cardiovascular. If the cause of death is uncertain, it is regarded as a cardiovascular death. For myocardial infarction, the universal definition is used [22], and bleeding events are defined according to the Bleeding Academic Research Consortium criteria [18]. Changes in antithrombotic medication are collected after 1 month, 1 year and 2 years by digital questionnaires. At 1‑year post-PCI, the use of cholesterol and DM medications is also collected. For non-responders, medication use is derived from the EHRs if available.

In Castor EDC, multiple tools are incorporated to guide data entry, such as settings for range and inserted explanatory texts or images. There is at least one study coordinator per site who has access to all records of this specific site in the EDC (study admin role). Furthermore, at least one study coordinator from each site is able to export the data of all sites. To reach a high degree of completeness, each centre can monitor their own data completeness in the EDC. Data are subject to the General Data Protection Regulation. In order to pseudonymise the data, no traceable personal data are stored in Castor EDC. Each site created and stored an identification log and stored it securely and separately at each site to retrace the patients back to the Castor identification number if required.

Data will be accessible to other researchers involved, such as interventional cardiologists from the participating centres, who can only add and view data of patients from their own site. A clinical event committee will periodically review 20% of the adverse events (randomly selected) to check whether all participating centres adhere to the same and the correct definitions of events. Furthermore, outcome differences between centres in the ZON-HR will be analysed to indicate possible gaps in the collection of certain outcomes in a centre. If one of the centres appears to monitor an outcome less well, extra follow-up checks within the EHR will be performed.

The ZON-HR is led by a steering committee comprising representatives of the participating sites and a statistician. Weekly meetings are held by the executive committee, consisting of the principal investigators of the Radboud university medical centre and Maastricht University Medical Centre+ (R.J.M. van Geuns and A.W.J. van ’t Hof), interventional cardiologists and researchers from the participating sites. Student researchers are appointed to contribute to the collection of follow-up data. All proposals for research questions or research requiring pooled data are submitted to the steering committee and can be executed after approval. The workflow of the ZON-HR is graphically depicted in Fig. 2.

Workflow of South-East Netherlands Heart Registry. PCI percutaneous coronary intervention, FU follow-up (figure was created with BioRender.com)