The prognosis of patients with intermittent claudication : a prospective cohort study

Abstract

The prognosis of the lower limb in patients with intermittent claudication (IC) is considered to be relatively benign and it is assumed that only 5-10% deteriorate to critical limb ischaemia (CLI) over 5 years. The perceived benign prognosis supports the recommendation of conservative management for the vast majority of patients. However, for those who progress rapidly to severe ischaemia, such an approach may lead to delayed intervention and an increased risk of morbidity. Early identification of patients at high risk of deterioration may potentially guide clinical decision making for selection of an interventional management approach at diagnosis. To test this hypothesis, four sequential studies were conducted with two primary foci. The first focus was to determine the rate of progression to CLI among patients with IC. The second was to determine whether prediction of impending rapid deterioration were possible, potentially allowing for an alternative management approach in high risk subgroups. A systematic review of the literature (Study 1) indicated a relatively low risk of deterioration to critical ischaemia among patients with IC but the evidence is unclear. A retrospective study (Study 2) of local referral patterns of patients with IC provided the groundwork for the main studies. Subsequently, a prospective observational cohort study of consecutive patients newly referred to the vascular unit in the national hospital was conducted (Studies 3 and 4). This research aimed to explore the prognosis of the lower limb among patients with IC over two years and to identify predictive factors for deterioration to CLI. The identified independent predictors were used to design a patient-specific predictive model to stratify patients’ risk of lower limb morbidity. One hundred fifty participants (119 men, 31 women; mean age 69.7 years, SD 9.3) were recruited and assessed for PAD by ankle brachial index (ABI), toe-brachial index (TBI) and Doppler waveforms at baseline, 12 months and 24 months following enrolment. Duplex scans were accessed to confirm PAD and/or medial arterial calcification. Diabetes, hypertension, hyperlipidaemia and smoking history were present in >70% of the cohort. Within two years 23.3% developed CLI and an additional 27.3% experienced significant haemodynamic deterioration (decline by t0.15 in ABPI and/or t0.1 TBI). Baseline ABPI d0.5, ABPI, TBPI, baseline TBPI d0.39, HbA1c and infrapopliteal artery disease were identified as independent predictors for the development of CLI within 2 years in patients with IC. A clinical patient-specific predictive model using the combined predictive value of baseline ABPI, TBPI and the presence of infrapopliteal artery disease was found to have a significant ‘good level’ predictive value for the development of CLI within two years (AUROC 0.82 p=<0.001). This work demonstrated that the prognosis of the patient with IC may not be as benign as previously assumed. Using the proposed predictive model, patients may be stratified as requiring close haemodynamic monitoring or requiring prompt evaluation for revascularisation. This new knowledge may potentially support clinical decision making at initial diagnosis allowing for an individualised approach to management of patients with IC, aiming to reduce morbidity in this population.