Editorial: Clinical trials in cardiovascular medicine: 2025—addressing residual cardiovascular risks through precision-guided approaches

Cardiovascular disease is the leading cause of morbidity and mortality worldwide 1 and its prevalence increases with population aging. Coronary heart disease (CHD) has ranked first in disease burden despite substantial advances in pharmacotherapy, interventional cardiology, and preventive medicine. Major risk factors for CHD include age, sex, family history, hypercholesterolemia, hypertension, diabetes, obesity, and lifestyle. Pathologically, metabolism disorder and dysregulated renin-angiotensinaldosterone system and autonomous nervous system contribute to the development of CHD. Inflammation, a convergent response of various risk factors, is involved in all stages of CHD pathogenesis, including atherosclerosis, unstable angina, myocardial infarction, cardiac remodeling, and heart failure 2,3 . Development of new treatments, particularly those that target residual risk beyond cholesterol-lowering, has been of substantial interest recently. These include clinical development of anti-inflammatory modalities, including blockers of interleukin 1β 4 and interleukin-6 5 , and colchicine 6,7 , which is the only approved drug for CHD, but with efficacy concerns 7 . Others include triglyceride lowering agents 8 , and lipoprotein (a) lowering agents 9 . Recent discovery of sodium-glucose cotransporter 2 inhibitors 10,11 and glucagon-like peptide-1 (GLP1) agonists 12,13 for cardiovascular benefits in diabetes patients fuels clinical endeavor of exploring these diabetes drugs for further cardiovascular benefits in non-diabetic patients. Meanwhile, advances in biomarker science, multimodality imaging, and systems biology are enabling investigators to target new mechanisms and those previously difficult to quantify, while allowing risk stratification and personalized treatment to improve cardiovascular outcome. The integration of pharmacological interventions, biomarkers, multi-omics technologies, advanced imaging, and digital health tools is therefore reshaping the landscape of translational cardiovascular research.This special issue on Clinical Trials in Cardiovascular Medicine 2025 published eleven clinical studies as summarized in Table 1.One of the most rapidly evolving areas is the management of residual cardiovascular risk following acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). Although contemporary antithrombotic therapy, intensive lipid lowering, and early revascularization have significantly improved outcomes, persistent inflammation and endothelial dysfunction continue to drive recurrent events. The Mono Antiplatelet and Colchicine Therapy (MACT II) trial is designed to evaluate an aspirin-free, inflammation-guided strategy combining ticagrelor monotherapy with colchicine, with treatment duration tailored by high-sensitivity C-reactive protein levels 14 . Similarly, the Xueshuantong injection trial protocol addresses myocardial injury and inflammatory risk in unstable angina using a biomarker-based assessment, reflecting growing interest in mechanism-oriented adjunctive therapies 15 .Attention has also shifted from achieving large-vessel patency alone toward improving downstream myocardial perfusion. The slow flow/no-reflow phenomenon during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) is a critical challenge. The pilot trial on electroacupuncture for slow flow/no-reflow provides preliminary evidence that this non-pharmacological intervention may improve coronary microvascular perfusion and reduce inflammation 16 .Autonomic imbalance and lifestyle factors are increasingly recognized as key contributors to hypertension and adverse cardiovascular outcomes. The SCRATCH-HTN trial (A Sham-Controlled Randomised Trial evaluating the Safety, Acceptability and Efficacy of Autonomic neuromodulation in Uncontrolled Hypertensive patients) is designed to investigate a novel, non-invasive transcutaneous vagal sensory stimulation for uncontrolled hypertension 17 , which may lead to development of devicebased, self-administered therapies. Furthermore, the caffeine and sleep deprivation trial 18 demonstrates that acute caffeine intake during total sleep deprivation exacerbates blood pressure elevation and inflammatory responses, underscoring the importance of balancing performance-enhancing strategies with cardiovascular risk in sleep-restricted populations.Precision cardiovascular medicine has accelerated the application of multi-omics and biomarker-guided risk stratification. The microRNA-29a (miR-29a) study 19 demonstrates that this microRNA is a novel biomarker for early detection of myocardial remodeling after AMI and it improves early diagnosis when combined with other biomarkers [N-terminal pro-B-type natriuretic peptide (NT-proBNP), and Soluble suppression of tumorigenesis-2 (sST2)]. The multi-omics profiling study in elderly patients with CHD and mild cognitive impairment uncovers shared molecular pathways, supporting the emerging concept of cardio-cerebral interaction 20 . The Shenqi Yangxin Formula trial uses coronary computed tomography angiographyderived parameters to evaluate the effect of the traditional Chinese medicine on plaque stabilization and residual risk in patients with stable coronary artery disease, embodying a precision-oriented, imaging-guided approach 21 .Finally, the scope of modern trials extends beyond coronary artery disease to chronic heart failure (HF), emphasizing functional capacity and quality of life. The FangJiHuangQi granule trial evaluates an adjunctive herbal therapy in HF patients using functional, biomarker, and patient-reported outcomes, reflecting a more comprehensive, patient-centered management paradigm 22 . Complementing this, the ginseng berry saponins trial in stable coronary artery disease 23 focuses on improving cardiorespiratory fitness, a key determinant of long-term prognosis. In addition, similar cardiovascular safety profile and potassium lowering effects were detected in hyperkalemic patients between levalbuterol and albuterol, two bronchodilator medications for pulmonary disease 24 .Collectively, these contemporary cardiovascular clinical studies address residual cardiovascular risk beyond current standard treatments by assessing traditional medicine, inflammation-targeted therapies and autonomic modulation, and uncover novel biomarkers and molecular signature. Together, they provide valuable insights that may inform new drug discovery and future strategies for individualized prevention and long-term cardiovascular disease management.