Clinical Trials in Older Adults with Cardiovascular Multimorbidity: A Perspective on Pragmatic Trial Design

Area of Science:

• Geriatric Cardiology
• Clinical Trial Methodology
• Cardiovascular Disease Research

Background:

• Population aging increases cardiovascular disease (CVD) burden in older adults with multimorbidity and frailty.
• Existing randomized clinical trials (RCTs) often use homogeneous participants, limiting applicability to complex geriatric populations.
• Geriatric cardiology requires trial designs that better reflect real-world patient complexity.

Purpose of the Study:

• To conduct a comparative methodological analysis of two European cardiovascular RCTs (HI-COR-65 and SENEKA).
• To propose a geriatric-oriented framework for improving future cardiovascular trial design in older adults with multimorbidity.
• To address limitations in current trial designs regarding representativeness, patient complexity, and outcome relevance.

Main Methods:

• Qualitative comparative analysis of two cardiovascular RCTs across five domains: population representativeness, clinical objectives, exclusion criteria, multidisciplinarity, and patient perspective.
• Evaluation of how trials operationalize geriatric complexity, stratification, and patient-centered outcomes.
• Review of intervention models and participation burden.

Main Results:

• Both analyzed trials made progress by including older adults with cardiovascular multimorbidity.
• Recurring limitations include inadequate operationalization of geriatric complexity, potential selection of robust participants, misaligned outcome hierarchies, and predominantly pharmacological, monodisciplinary interventions.
• Current trial designs often fail to fully integrate comprehensive geriatric assessment or patient priorities.

Conclusions:

• Future cardiovascular trials in older adults need pragmatic, complexity-sensitive designs moving beyond chronological inclusion.
• The proposed Comprehensive Geriatric Cardiology (COMGERCARDIO) framework integrates geriatric assessment, adaptive interventions, patient-centered outcomes, and stratified analysis.
• The COMGERCARDIO framework aims to generate scientifically robust, clinically usable, and equitable evidence for aging populations.