The long term prognosis of patients with peripheral arterial disease after infrainguinal bypass surgery : the follow-up of the Dutch Bypass and Oral anticoagulants or Aspirin Study

Peripheral arterial disease (PAD) is a major public health burden with a prevalence of approximately 27 million people in Europe and North America. PAD is characterised by a progressive narrowing or occlusion of the major arteries in the lower limbs as a result of atherosclerosis. Because atherosclerosis is a systemic disease, patients with PAD are at high risk of lower limb complications and of cardiovascular and cerebrovascular ischaemic events. Despite the growing awareness that PAD is an important marker of generalized atherosclerosis, its systemic consequences are still underestimated and undertreated in comparison with coronary artery disease or cerebrovascular disease. To raise awareness and improve secondary prevention, this thesis focussed on the long-term prognosis of patients with PAD who were treated with infrainguinal bypass surgery. Our primary aim was to quantify the risk of ischaemic complications throughout the whole arterial tree up to 10 years after bypass surgery and elucidate its determinants. Data on fatal and non-fatal vascular events that occurred between 1995 and 2009 were recorded in nearly 500 patients who had participated in the Dutch Bypass and Oral anticoagulants or Aspirin (BOA) Study (The Lancet 2000;355:346-351). The follow-up data were complete in 94% of patients and enabled us to give a fairly accurate insight in the long-term course of PAD and to produce an easy to use tool to determine a patient’s vascular risk profile. This so called BOA Risk Chart helps to predict a patient’s long-term prognosis quickly and effortlessly without the need for any additional testing. Furthermore, we studied the former and currently applied drug treatments (i.e. antithrombotic, antihypertensive, and lipid lowering drugs) and cardiovascular risk management in PAD patients after they underwent peripheral bypass surgery. Both the results of our international survey among vascular surgeons throughout Europe and of our drug registration over the past decade in a sample of patients from the Dutch BOA study showed an improvement in the application of secondary prevention therapy, but also for it to remain far from optimal. Although these results should be interpreted with caution because of possible selection and survival bias, they do underline the frequently reported undertreatment of patients with PAD. Lately, bleeding –the main adverse effect of antithrombotic therapy– is reported to lead to a four- to five-fold or even a nine-fold increase in the risk of death, myocardial infarction, or ischaemic stroke in patient with coronary artery disease or cerebrovascular disease. As this association has not been reported in PAD patients before, we studied the consequences of bleeding in patients with PAD from the Dutch BOA Study and again in a pooled dataset of the Dutch BOA Study and the Warfarin Antiplatelet Vascular Evaluation (WAVE) Trial (N Engl J Med 2007;357:217-227). Our results confirmed the previous findings of non-fatal major bleeding being independently associated with a three-fold increased risk of new ischaemic events. Further research is required to elucidate the causal underlying mechanism of this new association. Until then, the prevention of bleeding is equally important as the prevention of ischaemic events. Finally, in daily life the prognosis after peripheral bypass surgery is determined by a patient’s perception of health, rather than by clinical risk estimates. Therefore we studied the changes in patients’ health related quality of life (HR-QoL) after peripheral bypass surgery over time. Their HR-QoL was substantially impaired in comparison with the HR-QoL of the general population at the same mean age, even if the patient had a patent graft or experienced no other vascular event during follow-up. Over time their HR-QoL worsened, mainly their physical health, and especially after the occurrence of a vascular event. Given that peripheral bypass cannot prevent the HR-QoL in patients with PAD to deteriorate over time, atherosclerotic risk management through lifestyle modifications and drug treatments might be just as important to stabilise the HR-QoL for as long as possible. In conclusion, PAD is a major public health burden, not only because PAD has a high prevalence and a progressive pathology, but especially because its the long term systemic consequences are largely disabling and currently largely underestimated