Efficacy and safety of pharmacotherapy in COPD with arteriosclerosis: protocol for a systematic review and network meta-analysis

Introduction Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality. Arterial stiffness, an independent predictor of cardiovascular risk, enables detection of early vascular alterations preceding major clinical outcomes, making it critical for COPD management. Pharmacotherapy currently represents a major focus of therapeutic research for arterial stiffness modulation in this population. However, while current evidence supports specific pharmacological approaches, such as statins’ vascular modulation in certain subgroups, their clinical efficacy remains inconclusively demonstrated across trials. Methods and analysis To address this critical knowledge gap, we propose a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review and meta-analysis focusing specifically on COPD patients with concomitant arterial stiffness, aiming to evaluate the efficacy of vascular-targeted pharmacotherapies (statins, phosphodiesterase-4 inhibitors, long-acting bronchodilators). We conduct an extensive search across various databases (including MEDLINE and Embase, the Cochrane Central Register of Controlled Trials, Epistemonikos, Scopus, Web of Science Core Collection and China National Knowledge Infrastructure). The search will focus on randomised controlled trials (RCTs) of pharmacotherapy interventions associated with concurrent arteriosclerosis in COPD patients published from the date of creation of these databases to 1 May 2025. The primary outcome will be arterial pulse wave velocity, with secondary outcomes encompassing vascular function biomarkers, COPD clinical characteristics, systemic inflammatory markers (including tumour necrosis factor-alpha), clinical remission rate and adverse events. Two independent reviewers will systematically search seven biomedical databases using validated strategies, followed by risk-of-bias assessment (Cochrane RoB 2.0) and evidence quality grading (Grading of Recommendations Assessment, Development and Evaluation). Subgroup analyses will be initiated contingent on identification of significant statistical heterogeneity. Stratification variables may include, but are not limited to, disease severity (Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), cumulative smoking exposure (quantified in pack-years) and comorbidity burden (eg, cardiovascular/metabolic disorders). Both conventional pairwise and network meta-analyses will be implemented to hierarchically rank therapeutic interventions and identify the optimal regimen. Ethics and dissemination This systematic review protocol is based on published RCTs and does not contain private information about the patient; therefore, ethical approval is not required. PROSPERO registration number CRD42024628739.