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CAMHS won't see you now

Why continuity of care is under threat

Treatments have moved on in this

field and nearly all patients can be managed in primary care, as

Professor Gerard Stansby explains

Intermittent claudication (IC) ­ pain in the leg muscles on walking that resolves at rest ­ is a common and debilitating condition that affects between 1.7 and 7.1 per cent of those over 55 years.

It is also an under-recognised but powerful marker of increased cardiovascular risk.

Background IC is often the first symptom of peripheral arterial disease (PAD) and is usually due to widespread atherosclerosis; however, IC symptoms often go unreported by patients since they assume the 'cramp-like' pain on walking to be a sign of ageing or arthritis.

The pain is usually felt in the calves, although it can occur in the buttocks or thighs, after exercise. If the patient stops and rests, the pain disappears, but returns when they begin walking again. Very few other conditions can cause these types of symptoms.

The incidence of IC increases with age. Other risk factors include smoking, diabetes, impaired glucose tolerance, hypertension, dyslipidaemia, haemorrheological factors such as elevated fibrinogen levels and blood viscosity, and hyperhomocysteinaemia.

Smoking is by far the most important modifiable risk factor.

Fortunately, fewer than 10 per cent of patients with IC will progress to critical limb ischaemia (manifested by pain at rest and/or ulceration and gangrene) and only approximately 2 per cent will ever require amputation.

However, as already noted, the risks of mortality from cardiovascular causes, particularly acute MI, are high. In addition, patients with IC have a significantly reduced quality of life compared with age- and sex-matched controls.

Diagnosis and screening

Since patients often fail to spontaneously mention IC symptoms to clinicians, it is worth screening at-risk patients, particularly the over-50s, hypertensives, patients with diabetes, ischaemic heart disease or high cholesterol, smokers and ex-smokers attending smoking cessation clinics.

The simplest way to screen these patients is to ask the question: how far can you walk without pain?

Other key questions to ask if a patient describes pain or discomfort in their legs on walking are contained in the Edinburgh Claudication Questionnaire (see table on page 58).

Very few other conditions cause

pain only on walking. Spinal canal claudication usually produces heaviness, weakness or numbness rather than cramping pain in a muscle group. Absent femoral, popliteal and foot pulses are also indicative of IC.

A more objective assessment can be achieved by measuring the ankle-brachial pressure index (ABI) using a hand-held doppler. An ABI <0.9 is="" indicative="" of="">

Patients with suspected IC that significantly interferes with their lifestyle should be referred to a vascular surgeon for further assessment, though in most cases treatment can be managed successfully in primary care.

Management

The UK's first national consensus statement on the management of IC pinpointed secondary prevention to reduce overall cardiovascular risk as the clinical priority. However, the statement also recognises that for patients, the amelioration of symptoms to increase pain-free walking distance and improve quality of life is important, and this is particularly appropriate for older people.

Lifestyle modifications

The first component of IC management is treatment to reduce cardiovascular risk through lifestyle modifications and pharmacological therapy. Lifestyle modification consists of exercise programmes that encourage patients to walk through the pain, smoking cessation and dietary changes. Smoking cessation is essential and can almost double

10-year survival rates in claudicants.

Antiplatelet agent

An antiplatelet agent can reduce by almost a quarter the incidence of a composite outcome of ischaemic stroke, MI and vascular death in patients with symptomatic PAD. All patients with IC should therefore be considered for low-dose aspirin therapy (usually 75mg daily) and if this cannot be tolerated, clopidogrel 75mg daily.

Controlling blood pressure, lipids, cholesterol and blood glucose

Rigorous control of blood pressure and lipids is also recommended for all claudicants. Hypertension should be treated to target (systolic <140mmhg, diastolic=""><85mmhg) and="" may="" require="" the="" use="" of="" more="" than="" one="" antihypertensive="">

Weight reduction, reducing salt intake and increasing exercise may be adopted in the first instance.

However, if BP-lowering drugs are required, an ACE inhibitor should be considered. The HOPE study showed that the ACE inhibitor ramipril reduces cardiovascular morbidity and mortality in patients with PAD by around 25 per cent2.

Patients with hyperlipidaemia should also have their cholesterol levels lowered to target (total cholesterol <5mmol>

The Heart Protection Study3 showed that lowering total and LDL-cholesterol by 25 per cent with a statin reduces cardiovascular mortality and morbidity in PAD patients by around a quarter.

It also showed that the benefit of a statin occurs irrespective of cholesterol level; therefore all IC patients should be prescribed a statin if their cholesterol level is >3.5mmol/l.

IC is twice as common in people with diabetes. Patients with IC should therefore also be screened for the presence of diabetes and their blood glucose controlled if necessary.

Likewise, all people with diabetes should be regularly assessed for evidence of PAD.

Cardiovascular risk reduction strategies are not primarily designed to address claudication symptoms or improve walking distance ­ they aim to reduce overall risk.

For example, there is little evidence that smoking cessation alone actually improves claudication distance (although it reduces future cardiovascular risk).

Another key component of any management strategy for IC should therefore be to focus on symptomatic treatment, either through exercise programmes, pharmacotherapy or endovascular or surgical intervention.

Improving symptoms can help IC patients comply with other aspects of their treatment as well as improving their health-related quality of life.

Exercise and drugs that can help

Exercise programmes help IC patients to significantly increase the distance they can walk without pain ­ if they adhere to the programme. The most effective exercise regimen consists of three supervised walking sessions a week on a treadmill, designed to encourage patients to 'walk through the pain'.

Over a period of an hour the patient walks to near maximal pain, stops until the pain is relieved, and then resumes walking to near maximal pain again.

Unfortunately only a minority of patients in the UK are able to attend supervised exercise classes and compliance has been shown to be poor in some studies.

In addition, such classes are expensive to run and are not widely available.

Improving walking distance using pharmacotherapy can help IC patients comply with other aspects of their treatment. Five drugs have been approved for the treatment of IC symptoms in the UK: pentoxifylline (oxpentifylline), naftidrofuryl, inositol nicotinate, cinnarizine and, most recently, cilostazol. Cilostazol is probably the first-line drug of choice in selected patients, based on currently available clinical trial data.

There are six published multicentre phase III trials with cilostazol involving 1,751 patients with IC4-9, and a recent meta-analysis included data from two further unpublished studies, bringing the total number of patients studied in phase III trials to 2,702.

In these studies cilostazol significantly increased walking distances and quality of life in patients with IC when compared with placebo.

The increase in the mean maximal walking distance varied from 28-100 per cent with cilostazol 100mg twice daily, compared to 10-28 per cent for placebo.

Patients treated with cilostazol reported significant improvement in all walking impairment measures including walking distance, speed, stair-climbing ability and calf-pain severity compared to patients allocated to placebo (p<>

However, cilostazol is contraindicated in several subpopulations of patients, particularly those with congestive heart failure and severe hepatic or renal impairment.

Most claudicants can be managed without invasive therapies (angioplasty or surgery) and many will improve after a period of conservative management with an emphasis of risk-factor reduction.

Balloon angioplasty

Percutaneous balloon angioplasty has been shown to be effective in improving walking distance and health-related quality of life in selected patients, but has limited durability in the long-term, and many lesions may be technically unsuitable for angioplasty.

Balloon angioplasty is therefore usually reserved for claudicants with major impairment of quality of life despite a period of appropriate conservative therapy.

Surgery

Vascular surgical bypass (for example, femoro-popliteal bypass) is associated with a significant risk of complications, including limb loss, and is usually reserved for those patients with severe disabling claudication in whom other therapies have not been effective.

Conclusion

The prevalence of IC is likely to increase with an ageing population. While IC may be seen as a relatively minor problem, it is in fact a marker of serious cardiovascular disease as well as the first recognisable symptom of PAD.

It is therefore essential that health care professionals screen at-risk patients for pain on walking.

Prompt treatment of risk factors is essential to reduce the risk of subsequent mortality from cardiovascular and coronary heart disease.

However, symptom relief is also important since it can act as an incentive to patients to comply with the lifestyle modifications necessary to further reduce cardiovascular risk. Exercise programs are useful but unfortunately are not widely available.

For those patients who have major impairment of quality of life despite appropriate management, invasive treatments such as angioplasty may be considered.

Among the limited options available for these patients, current data also appears to support the use of cilostazol.

References

1 Leng GC, Fowkes FGR. The Edinburgh Claudication Questionnaire: An improved version of the WHO/Rose questionnaire for use in epidemiological surveys. J Clin Epidemiol 1992;45:1101-9

2 The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin converting enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. New Engl J Med 2000;342(3):145-53

3 Heart Protection Study Collaborative Group. MRC/BHF Heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.

Lancet 2002;360:7-22

4 Money SR et al. Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease.

J Vasc Surg 1998;27:267-75

5 Elam MB et al. Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication. Arterioscler Thromb Vasc Biol 1998;18:1942-7

6 Dawson DL et al. Cilostazol has beneficial effects in treatment of intermittent claudication. Circulation 1998;98:678-686

7 Dawson DL et al. A comparison of cilostazol and pentoxifylline for treating intermittent claudication. Am J Med 2000;109:523-30

8 Strandness DE Jr et al. Effect of cilostazol in patients with intermittent claudication:

a randomised, double-blind, placebo-controlled study. Vasc Endovasc Surg 2002;36:83-91

9 Beebe H et al. A new pharmacological treatment for intermittent claudication ­ results of a randomised, multicentre trial. Arch Intern Med 1999;159:2041-2049

Gerard Stansby

is professor of vascular surgery, University of Newcastle, Northern Vascular Centre, the Freeman Hospital, Newcastle upon Tyne

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