Presentation (CTI)

OBJECTIVES: To determine whether cross-national variation in cardiovascular-kidney-metabolic (CKM) mortality protection reflects structural insurance inequality or pharmacological heterogeneity, and to assess implications for transferability of real-world value evidence across health system architectures.
METHODS: Target trial emulation within a multi-state framework was applied to harmonised longitudinal data from six nationally representative ageing cohorts (CHARLS, ELSA, HRS, KLoSA, MHAS, SHARE; n ≈ 144,000) spanning five insurance architectures from approximately 14% to near-universal coverage. Per-protocol causal estimates quantified pharmacological treatment effects on mortality from two CKM states: hypertension/type 2 diabetes and established cardiovascular disease. Random-effects meta-analysis assessed between-system heterogeneity before and after causal adjustment. Life-course medication trajectory analysis identified treatment access patterns using optimal sequence matching.
RESULTS: Pharmacological treatment causally reduced mortality in hypertension/type 2 diabetes (RR 0.810, 95% CI: 0.745-0.883) and established cardiovascular disease (RR 0.805, 95% CI: 0.726-0.895). After causal adjustment, between-system heterogeneity in the primary mortality pathway (HTN/T2D→Death) collapsed from I² = 80.2% to 0.0% (p = 0.865); for CVD→Death, heterogeneity was reduced from 87.4% to 64.0% (p = 0.062). Unadjusted estimates showed substantial apparent heterogeneity (I² = 80-87%), driven by a structural coverage-confounding gradient: in low-coverage settings, treatment concentrated among the severely ill suppressed the protective signal. Dose-response analysis confirmed a monotonic mortality gradient (three drug classes: RR 0.771; trend p < 0.0001). Five life-course trajectories were identified; sustained multi-drug use was the most protective pattern, most prevalent under mandatory single-payer coverage, and independently predicted by insurance and education.
CONCLUSIONS: CKM pharmacological benefit is architecturally invariant across five health system types, supporting transferability of value evidence for health technology assessment and reimbursement decisions. Cross-national mortality inequality is structurally produced by differential insurance coverage rather than pharmacological variation. Expanding coverage, eliminating out-of-pocket costs, and strengthening primary care are key structural levers for realising the population-level value of existing CKM therapies.