Lost in translation: Why ‘lost to follow-up’ matters

Abstract

Lower extremity peripheral vascular interventions (PVI) are important for symptom treatment and limb salvage in patients with symptomatic peripheral artery disease (PAD). After PVI, short-term follow-up with the proceduralist allows for the opportunity to ensure adherence with medications, assess for clinical improvement, and obtain postprocedure noninvasive testing of the limb. The patient’s symptom status, clinical exam, and noninvasive test results all reflect a primary outcome of interest: vessel patency. This focus on vessel patency in clinical practice parallels the design of peripheral device trials, in which vessel patency is almost always the primary endpoint. However, following a peripheral revascularization, patients with PAD are at high risk for long-term cardiovascular and limb ischemic events and mortality.1,2 Therefore, optimizing post-PVI outcomes and understanding the safety of new therapies in this population require longer-term follow-up past the traditional peri-procedural timeframe. In this issue of Vascular Medicine, Wang and colleagues examine the phenomenon of loss to follow-up among patients with PAD undergoing PVI using data from the PVI Registry of the Vascular Quality Initiative.3 Among the 39,342 patients included in this study, the rate of follow-up at 1 year was 91.6%. Compared with participants who had complete follow-up data, patients who were lost to follow-up were more often male, of non-white race, had a greater burden of comorbidities, and more frequently presented with critical limb ischemia. Patients lost to follow-up also were more likely to have post-procedure complications requiring admission and were less likely to be discharged on aspirin, P2Y12 inhibitor, or statin. After multivariable-adjusted modeling, older age, male sex, use of dialysis, more severe American Society of Anesthesiology class, and longer fluoroscopy time were associated with higher risk of loss to follow-up. The authors additionally examined survival in this study. They demonstrated that over a period of up to 8 years, patients remaining in follow-up had significantly better survival than those lost to follow-up (83.5% vs 43.2%, p < 0.001). In particular, follow-up in the office was associated with greater survival than phone follow-up. After multivariable adjustment, loss to follow-up at 1 year was associated with a 6.56-fold greater risk of death. Although patient follow-up is important for many reasons, causality regarding post-procedural follow-up and its association with increased survival cannot be inferred from this observational study due to a high risk of unmeasured confounding. Consistent with the baseline characteristics of those lost to follow-up, it is likely that these patients were sicker and had more severe disease, resulting in a higher risk of mortality. Nevertheless, these observations contribute to efforts to better understand outcomes and to optimize care for patients with PAD. In general, patients with PAD represent an understudied population. One of the challenges in caring for this population is the fragmentation of care provided, as patients may receive vascular treatment from multiple medical specialties, including cardiology, vascular medicine, vascular surgery, and interventional radiology. Patients with PAD also typically have comorbidities requiring additional visits, not only with their internist or other primary care provider but also with other specialists. Given the multiple clinicians caring for patients with PAD, there may be faulty provider assumptions regarding who is following and optimizing the patient’s medical treatment, resulting in underutilization of guideline-recommended therapies. The patient also may not understand the role of each provider, especially post-PVI, which may increase the risk of missing appointments. Beyond the implications for patient care and improving outcomes, complete patient follow-up is critically necessary to fully understand the risks and benefits of both investigational and established therapies. Clinical trials typically define a primary efficacy endpoint for which the sample size and number of efficacy events is pre-specified to achieve statistical significance. In contrast, safety assessments are descriptive and limited to the sample size, duration of follow-up of Lost in translation: Why ‘lost to follow-up’ matters