The impact of long-term adherence to guideline-directed medical therapy on outcomes in peripheral artery disease

Peripheral artery disease (PAD) is a prevalent manifestation of systemic atherosclerosis associated with high cardiovascular risk. 1 Guideline-directed medical therapy (GDMT), including antiplatelet agents, lipid-lowering therapy, and renin-angiotensin system inhibitors (RAASi), reduces adverse outcomes, 2,3 yet uptake and adherence in PAD remain suboptimal compared with other atherosclerotic conditions, such as coronary or cerebrovascular disease.4,5 Therapy initiation at discharge has been studied, 4-6 yet the long-term prognostic significance of sustained adherence in PAD populations remains insufficiently characterized.We conducted a nationwide retrospective cohort study including all patients hospitalized with PAD in Slovenia between January 1, 2015 and June 30, 2021, with a median follow-up of 34.5 (IQR: 16.8-53.8)months.Data were linked across the Hospital Discharge Statistics Database, the National Mortality Registry, and the Medication Reimbursement Database.PAD diagnoses were identified using International Classification of Diseases, Tenth Revision (ICD-10) code I70.x.Adherence was assessed from pharmacy dispensation data using a continuous measure of adherence (CMA7), 7 calculated within rolling 120-day windows, with overlap and carry-over of surplus medication.7 Adherence was modeled as a time-varying covariate, both continuously and dichotomized at ⩾ 80%.8 Each CMA was divided by 10 so that a one-unit change in the hazard ratio (HR) corresponded to a 10% absolute change in adherence.In addition to class-specific adherence, we created composite GDMT adherence measures: (i) an ordinal count (zero to three classes adherent at CMA7 ⩾ 80%) across antiplatelet, lipid-lowering, and RAASi therapy; and (ii) a binary composite (adherent to all three vs fewer than three).The primary outcome was a composite of all-cause mortality or hospitalization for nonfatal myocardial infarction, ischemic stroke, or PAD-related events.Associations were analyzed using multivariable Cox regression with time-dependent covariates, adjusted for age, sex, comorbidities, disease severity, andThe impact of long-term adherence to guideline-directed medical therapy on outcomes in peripheral artery disease