improve claudication and reduce the risk of vascular events. There is a need to establish smoking cessation clinics to deliver specialist care. All clinicians should try to motivate patients to quit by spending a few minutes explaining why smoking is harmful to them.

Antiplatelet Agents

This patient could not tolerate aspirin. It is estimated that this problem arises in 10–15% of patients who are prescribed aspirin. There are several alternatives:

•“Cover” aspirin with a proton pump inhibitor (e.g. omeprazole).

•Eradicate Helicobacter pylori infection, if present.

•Use clopidogrel: the effectiveness of clopidogrel is based on the findings of major trials (e.g. CAPRIE, CREDO and CURE), but there is no study specifically designed to assess the effectiveness of this drug in PAD.19 However, patients with PAD had significantly fewer events on clopidogrel than on aspirin in the CAPRIE trial. Unfortunately, this conclusion is limited by the fact that PAD subgroup analysis was not included in the trial protocol.20

Due to his intolerance of aspirin, this patient was prescribed clopidogrel 75 mg/day. He tolerated this antiplatelet agent without any problems.

Potential limitations associated with the use of aspirin and/or clopidogrel have inspired clinical investigation into several promising new antiplatelet agents as potential additions or alternatives to standard therapy. The candidates include prasugrel, which has a mechanism similar to that of clopidogrel but with superior pharmacokinetics; ticagrelor, a nonthienopyridine that binds reversibly to the platelet P2Y(12) receptor; cangrelor, an intravenously administered analogue of ticagrelor; and various thrombin receptor antagonists. Current evidence derives from research in cardiovascular disease. Future studies will establish the role of these new therapeutic options in the treatment of PAD.21

Blood Pressure (BP)

Strict control of blood pressure (BP) in high risk patients is essential (<140/90 mmHg, ideally around 120/80 mmHg).20 In order to achieve this objective, there may be a need to use several antihypertensive drugs. Some general recommendations are appropriate:

•Several experts suggest that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB) should be avoided or used with caution in PAD because these patients may have renal artery stenosis. If an ACE inhibitor or ARB is used, the plasma creatinine concentration should be monitored soon after starting treatment (initiate treatment at the lowest dose).

•There is some debate as to whether beta-blockers adversely affect lower limb circulation in patients with PAD. It would appear reasonable, however, to use a beta-blocker in post-MI patients with PAD.

•Some BP drugs exert beneficial or adverse effects on lipid levels, haemostatic factors and perhaps more importantly, the long-term risk of developing diabetes.

Glucose Status

This topic was discussed above. It is also important to note that if the patient is diabetic, the blood pressure targets become stricter, especially if proteinuria is present (<130/80 mmHg).

Lipids

This topic has been discussed above.

Emerging Risk Factors

These factors1,5 include:

•Lipoprotein (a) (Lp(a)): there is evidence that Lp(a) is a marker of vascular risk, especially in patients with a raised serum LDL-C. Raised Lp(a) levels may also predict the risk of restenosis after surgery for PAD.17 Serum Lp(a) levels are difficult to lower, but the risk associated with this abnormality may decrease if the LDL-C level is markedly reduced. Correcting hypothyroidism is associated with a fall in serum Lp(a) levels. Similarly, postmenopausal hormone therapy (HT) may reduce serum Lp(a) concentrations. There are, as yet, no intervention trials to show that lowering serum Lp(a) levels (e.g. by using high doses of nicotinic acid) is associated with fewer vascular events.

•Homocysteine: raised plasma levels of homocysteine are thought to predict vascular risk possibly by acting synergistically with established risk factors. The link between homocysteine and PAD appears to be stronger than with CHD.5 However, there is no evidence from intervention trials to show that lowering plasma homocysteine levels (e.g. by folic acid, vitamin B12 or B6 supplements) is associated with a reduced risk of vascular events.

•Haemostatic and fibrinolytic factors: plasma fibrinogen concentration may be a predictor of vascular risk. The levels of this coagulation factor also predict the progression of PAD and possibly the risk of restenosis following bypass surgery.17 Plasma fibrinogen levels can be lowered by some fibrates used to treat dyslipidaemia. However, as with other emerging risk factors, no trial-based evidence is available to show that lowering fibrinogen levels is associated with a decreased risk of vascular events. There is less evidence linking fibrinolytic factors with vascular risk.

•Markers of inflammation (e.g. high-sensitivity C-reactive protein, CRP): serum CRP levels predict the risk of a vascular event even when there is no vascular disease present orwhenlipidlevelsare“normal”.WedonotknowwhetherCRPjustreflectstheinflammatory component of atherosclerosis or whether it is actually involved in its ­pathogenesis. Statins and fibrates lower serum levels of CRP.20 Recent evidence suggests that we should also consider CRP levels (in the high sensitivity range) as a target for treatment.22

Question 4

Is it relevant to monitor renal function in this patient?

Yes, because about 33% of PAD patients have atherosclerotic renal artery stenosis.5 It is therefore important to consider this diagnosis, especially if renal function tests are abnormal.Thereisevidencethatrenalandvasculardiseaseprogressinparallel.23 Increased plasma creatinine levels are associated with a higher risk of vascular events, even if these values are in the upper end of the reference range. There is evidence that statins exert a renoprotective action in patients with CHD or PAD.24,25 Impaired renal function may contribute to hyperuricaemia and hyperhomocysteinaemia.26 These variables may predict increased vascular risk.

References

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