Description

Background Cardiovascular disease (CVD) and chronic kidney disease (CKD) frequently coexist and together constitute a major global health burden associated with substantially increased morbidity, mortality, and healthcare utilisation. Importantly, the coexistence of CVD and CKD predisposes patients to heart failure with preserved ejection fraction (HFpEF), a complex clinical syndrome characterised by a high symptom burden, impaired quality of life, and a poor prognosis. HFpEF accounts for approximately half of all heart failure cases and may further aggravate the progressive interaction between cardiovascular and renal dysfunction.

Over the past decade, major therapeutic advances have improved outcomes in patients with CVD, CKD, and HFpEF. Large randomised trials, including DELIVER and EMPEROR-Preserved, have demonstrated that sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) improve clinical outcomes in patients with HFpEF. Renin-angiotensin system inhibitors and SGLT2 inhibitors also reduce adverse outcomes in patients with CKD. Furthermore, emerging evidence supports the use of non-steroidal mineralocorticoid receptor antagonists in patients with HFpEF or CKD.

Despite this strong evidence base, the implementation of guideline-directed treatment remains suboptimal. In a pilot study conducted at the study centre, only one-third of patients with coexisting CVD and CKD received fully optimised CKD treatment, consistent with findings from similar studies. Consequently, the principal challenge is no longer solely the development of effective therapies, but also the systematic implementation of existing evidence-based treatments in patients with complex multimorbidity.

Current care models are predominantly fragmented, with cardiology, nephrology, and primary care operating independently. This fragmentation leads to suboptimal coordination, delayed treatment optimisation, and inconsistent application of guidelines.

The OPTICARE Trial addresses this gap by evaluating a structured, multidisciplinary cardiorenal care model designed to optimise treatment in accordance with current clinical guidelines. The investigators hypothesise that this model will significantly improve cardiovascular and renal outcomes compared with standard care and has the potential to transform clinical pathways and future guideline recommendations.

Purpose and hypothesis The aim of this randomised trial is to evaluate the effectiveness of a systematic, specialised, multidisciplinary cardiorenal intervention, delivered through a Cardio-Renal Clinic, in improving cardiovascular and renal outcomes, reducing mortality and symptom burden, and improving quality of life and physical performance in patients with CVD and CKD.

The project consists of two studies. Study One will evaluate the short-term effects of multidisciplinary cardiorenal care after one year. Study Two will evaluate its long-term effects of the multidisciplinary cardiorenal care after five and ten years.

The investigators hypothesise that a specialised, multidisciplinary Cardio-Renal Clinic delivering guideline-directed cardiorenal care will improve cardiovascular, renal, functional, and patient-reported outcomes compared with standard care.

Methods The OPTICARE Trial is a single-centre, randomised, controlled, open-label, parallel-group trial including 500 participants with coexisting CVD and CKD.

At baseline, participants will undergo a comprehensive assessment comprising:

• Current clinical status and symptoms
• Cardiovascular and renal medical history
• Family history of cardiovascular and kidney disease
• Current medical treatment
• Lifestyle factors
• Patient-reported outcomes, including the KCCQ-12 and EQ-5D-5L questionnaires

Clinical examinations and investigations at baseline will include:

• Echocardiographic assessment of cardiac structure and function at rest and during exercise
• Assessment of volume status
• Blood pressure measurement
• Anthropometric measurements, including height, weight, body mass index, waist-to-hip ratio, and waist-to-height ratio
• Assessment of physical function using the 6-minute walk test and the 1-minute sit-to-stand test
• Blood and urine tests to assess cardiovascular and renal biomarkers
• A standard 12-lead electrocardiogram
• Estimation of cardiovascular and renal risk Participants will be randomised in a 2:1 ratio to either multidisciplinary care in the Cardio-Renal Clinic or standard care.

Participants assigned to the Cardio-Renal Clinic will undergo systematic assessment and optimisation of treatment. The treatment algorithm will be based on current national and international clinical guidelines for the management of CKD, HFpEF, hypertension, dyslipidaemia, and thromboembolic risk. Additionally, participants will receive counselling on diet, physical activity, smoking cessation, alcohol consumption, weight management, and recommended vaccinations.

All treatment decisions will be based on current national and international clinical guidelines and established evidence-based practice. Treatment decisions will be supported by a decision-support algorithm integrated into REDCap. The algorithm will be updated when relevant guideline recommendations change.

Following treatment initiation or adjustment, clinical and biochemical follow-up will be arranged as clinically indicated and in accordance with current guideline recommendations.

Participants assigned to standard care will continue existing treatment without any intervention by the study team. Participants will be encouraged to continue prescribed medications and attend planned appointments with general practitioners and relevant outpatient clinics.

A comprehensive follow-up visit will be conducted one year after randomisation to evaluate the short-term effects of the intervention. The principal baseline examinations and assessments will be repeated at this visit.

After five and ten years, medical records will be reviewed to identify major cardiovascular and renal events. The five- and ten-year follow-up will contribute to the evaluation of the long-term effect of the specialised, multidisciplinary treatment provided in the Cardio-Renal Clinic.

Sample size estimation The sample size calculation is based on the long-term primary composite cardiorenal endpoint. This endpoint resembles the composite kidney and cardiovascular outcome evaluated in the DAPA-CKD trial. Among participants without diabetes in DAPA-CKD, a hazard ratio of 0.50 was reported.

Assuming a two-sided significance level of 0.05, a statistical power of 80%, and a 2:1 allocation ratio, a total of 74 primary endpoint events are required to detect the anticipated treatment effect. Assuming an annual event rate of 6% in the control group and a planned follow-up period of five years, 464 participants are estimated to provide the required number of events. To account for withdrawal and loss to follow-up, a total of 500 participants will be included.

Expected contribution This research project aims to improve the care of a high-risk patient population with treatment needs that may not be adequately addressed within existing, specialty-specific models of care. By strengthening early detection, multidisciplinary collaboration, and the implementation of guideline-directed treatment, the project has the potential to improve both short- and long-term patient outcomes.

Beyond the potential benefits to study participants, the project may contribute to the development of integrated care models within the public healthcare system. The Cardio-Renal Clinic is intended to provide a scalable and resource-efficient model that could improve continuity of care, reduce fragmentation between medical specialties, and support more individualised, evidence-based treatment pathways. If successful, the project may serve as a framework for future cardio-renal clinics in Denmark and internationally.