Peripheral arterial disease Prognosis

Lower-limb complications
A minority of patients with intermittent claudication suffer from worsening leg symptoms (rest pain, ischaemic ulceration or gangrene). Estimates of the proportion of patients with intermittent claudication needing intervention, such as angioplasty or bypass surgery, vary considerably, but are of the order of 10%–20%, with only 1%–2% of patients progressing to amputation over five years. Continued smoking, diabetes and a low initial ABPI are the main risk factors for progression to amputation.

Systemic complications
While most patients fear amputation, it is cardiac or cerebrovascular events that are the major threats to handicap-free survival.

PAD is associated with a fourfold increase in the risk of cardiovascular death, from about 1% per year among control subjects to 4%–6% per year among patients with PAD. The more severe the PAD as measured by the ABPI, the worse the prognosis. Patients with symptomatic PAD have a 15-year accrued survival rate of about 22%, compared with a survival rate of 78% in patients without symptoms of PAD. Patients with critical leg ischaemia, who have the lowest ABPI values, have an annual mortality of 25%.

Reducing the burden of cardiovascular disease
Much of the evidence pertaining to primary and secondary prevention of cardiovascular events in patients with PAD has been extrapolated from observational and case–control studies of patients with PAD, and randomised-controlled trials in patients with coronary heart disease. The evidence we discuss here for the use of interventions is graded according to the National Health and Medical Research Council system for assessing levels of evidence. Unfortunately, not all of the interventions known to reduce cardiovascular mortality will necessarily improve the symptoms of intermittent claudication.

Smoking cessation (level of evidence, E32)
Smoking cessation remains a priority for all smokers — the survival benefit from cessation is unequivocal. Over 80% of patients with PAD are current or ex-smokers. The association between smoking and PAD is about twice as strong as that with coronary heart disease. Smoking results in earlier onset of symptoms and the severity of PAD increases with the number of cigarettes smoked. For patients with intermittent claudication, previous smoking has a long legacy of increased risk of PAD. It is important to emphasise to patients with symptomatic PAD that their leg symptoms will probably worsen, the results of any intervention will be less successful and the risks of amputation greater if they continue to smoke. Strategies for helping patients quit smoking have been reviewed elsewhere.

Exercise and weight loss (E1)
There is ample evidence that regular exercise is good for cardiovascular health. There is also evidence that exercise can improve walking distance in patients with intermittent claudication. It is likely that a structured or supervised program is most effective, particularly for older patients. Weight loss is generally associated with improved cardiovascular health and, in the case of intermittent claudication, it should, for obvious reasons, result in an increased walking distance.

Treatment of hyperlipidaemia (E2) and hypertension (E2)
The association between hyperlipidaemia and PAD is not as strong as it is with coronary heart disease. There is, however, recent evidence that lipid-lowering with a statin may improve walking distance in patients with intermittent claudication. More importantly, the Heart Protection Study reported that simvastatin (40 mg daily) use in patients with PAD (including those without prior coronary heart disease) resulted in a highly significant 25% proportional reduction in all major vascular events. For this reason alone, a statin should be considered for all patients with PAD, although the threshold cholesterol level for qualifying for a Pharmaceutical Benefits Scheme authority prescription is still higher for PAD than coronary heart disease (> 6.5 mmol/L v 4.0 mmol/L30).

Intervention trials in hypertension have not included intermittent claudication as an endpoint. It is unlikely that controlling hypertension will improve intermittent claudication, but it will reduce the risk of other cardiovascular events, particularly stroke.

Treatment of diabetes (E2)
Diabetes is important in PAD for a number of reasons. Patients with diabetes are prone to medial calcification (Monckeberg’s sclerosis) of lower-limb arteries in particular. While not an occlusive process, this pattern of calcification is a marker of poor prognosis. Good glycaemic control has the potential to prevent, or at least delay, amputation in patients with diabetes. This is primarily through preventing neuropathy and its associated ulceration and infection rather than stopping progression of any macrovascular PAD. Intensive glycaemic control also reduces the risk of other diabetes-related microvascular disease, particularly renal and ocular complications.

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