Incomplete Follow-Up and Competing Risks as Sources of Bias in Vascular Surgical Investigations

Background/Objectives: The aim of this study was to determine whether incomplete follow-up and competing event risks may be associated with the clinical course after treatment and with known risk factors, such as chronic limb-threatening ischemia (CLTI), in peripheral artery disease (PAD) patients. Methods: Patients hospitalized with PAD who were treated by endovascular or open-surgical means and followed up were included in this retrospective observational study. The primary outcome was reintervention-free survival (RFS); the secondary outcomes and competing events were major amputation and death. The follow-up index (FUI), defined as the ratio between the real and the maximal follow-up interval, was determined for each patient. Results: The FUI depended significantly on the disease stage of CLTI (estimate: -0.16; p: 0.003), endovascular (0.17; p: 0.007) or open-surgical intervention (0.21; p: 0.007) and intra-hospital re-operation (-0.29; p: 0.002) and tended to decrease with age (-0.004; p: 0.09). Independent of disease stage, patients with claudication or CLTI with an FUI < 0.5 had shorter RFS than patients with a FUI ≥ 0.5 (Cox regression, p: 0.07; log-rank test, p: 0.03). When both the FUI and competing risks were considered using Fine-Gray regression analysis, CLTI was associated with RFS (p: 0.016), while FUI (p: 0.004), CLTI (p < 0.001), and the involvement of common femoral (p < 0.001) and posterior tibial arteries (p < 0.001) were associated with major amputation-free survival. Conclusions: Incomplete follow-up is associated with advanced PAD and may itself mask a worse outcome, such as reintervention, restenosis, major amputation, or death. Competing events should also be considered potential sources of bias. Therefore, the FUI and competing events should be reported, and conclusions should be drawn cautiously in both observational and randomized prospective clinical studies.