Medication nonadherence is associated with higher morbidity after lower extremity revascularization in patients with peripheral arterial disease.

Abstract

Objective: Medical management of peripheral artery disease (PAD) consists of antiplatelet therapy, cholesterol reduction, blood pressure control, and anticoagulation. These medications lead to lower mortality, improved quality of life, and fewer adverse limb events in patients with PAD. However, few studies have examined medication adherence rates, the factors that influence them, and the subsequent effect on outcomes.

Methods: We identified all patients who underwent lower extremity endovascular revascularization for PAD between May 2022 and November 2024. Pharmacy dispensing reports were utilized to calculate the proportion of days covered for 90 days postoperatively for antiplatelet agents, anticoagulants, statins, antihypertensives, insulin, and other antihyperglycemic agents. We evaluated the factors associated with nonadherence (defined as composite proportion of days covered of <80%) and the association between nonadherence and reintervention, minor and major amputation, and 90-day mortality.

Results: Our study population included 405 patients, of which 45% were female, 39% Hispanic, 18% current smokers, 22% had claudication, and 78% had chronic limb-threatening ischemia (CLTI). Nonadherence rates ranged from 21.7% for sulfonylureas to 54.1% for short-acting insulin. In our sample, 62% met the criteria for composite adherence. Patients with CLTI had 45% lower composite medication adherence compared with that for claudicants (87.7% vs 78.1%; P = .046). Moreover, 97 patients underwent reintervention (24%), 68 (17%) underwent minor amputation, 39 (10%) underwent major amputation, 149 (37%) were readmitted within 90 days, and 16 (4%) died within 90 days. While no difference was noted in mortality (P = .90) between adherent and nonadherent patients, medication adherence was associated with a 61% lower risk of death-censored reintervention (subdistribution hazard ratio [sHR], 0.39; 95% confidence interval [CI], 0.27-0.58, P < .001), 56% lower risk of death-censored major amputation (sHR, 0.44; 95% CI, 0.23-0.84; P = .01), and 45% lower risk of death-censored minor amputation (sHR, 0.55; 95% CI, 0.34-0.90; P = .02). Patients on dialysis had a higher risk of minor amputation (P = .007), and patients with CLTI had higher risks of reintervention (P = .017) and minor amputation (P = .032). Insurance status and area deprivation index were not associated with composite adherence.

Conclusions: Medication nonadherence significantly increases the risks of reintervention and major/minor amputation following lower extremity endovascular revascularization. A significant proportion of patients are nonadherent to their medications following revascularization. Patients with CLTI comprise a high-risk group for nonadherence, with high rates of reintervention and amputation. Notably, traditionally accepted risk factors such as area deprivation index and insurance were not associated with adherence, suggesting that significant work is warranted to understand the reasons why patients are nonadherent to medications.