Peripheral arterial disease
INTRODUCTION: Up to 20% of adults aged over 55 years have detectable peripheral arterial disease of the legs, but this may cause symptoms of intermittent claudication in only a small proportion of affected people. The main risk factors are smoking and diabetes mellitus, but other risk factors for cardiovascular disease are also associated with peripheral arterial disease. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for people with chronic peripheral arterial disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010. Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review. We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 70 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antiplatelet agents, bypass surgery, cilostazol, exercise, pentoxifylline, percutaneous transluminal angioplasty (PTA), prostaglandins, smoking cessation, and statins.
Cassar K. Peripheral arterial disease. Clinical Evidence 2011; 01:211.
Substantive changes at this update
Antiplatelet agents Two new systematic reviews added comparing antiplatelet agents versus placebo.The first review found no significant difference between aspirin and placebo in cardiovascular events (non-fatal MI, non-fatal stroke, and cardiovascular death), all-cause mortality, or the occurrence of major bleeding.  The second review found that antiplatelet agents (ticlopidine, cloricromen, mesoglycan, indobufen, and defibrotide) increased maximal walking distance compared with placebo.Categorisation unchanged (Beneficial).
Exercise One RCT added, which found that a 12-week supervised arm crank exercise programme improved pain-free and maximal walking distances in men with stable intermittent claudication when compared with no exercise. The RCT found no significant difference between exercise and control in resting ankle brachial index. Categorisation unchanged (Beneficial).
Bypass surgery Long-term follow-up of one RCT  identified by an already reported review added. The RCT found no significant difference in all-cause mortality at 2 years between bypass surgery and percutaneous transluminal angioplasty (PTA), although beyond 2 years up to the trial end point (maximum 7 years' follow-up), it found bypass surgery improved survival compared with PTA. Categorisation unchanged (Likely to be beneficial).
Statins (HMG-CoA reductase inhibitors) One new systematic review added comparing statins versus placebo. The review found that statins increased maximal walking distance compared with placebo. Categorisation unchanged (Likely to be beneficial).
Percutaneous transluminal angioplasty (PTA) One systematic review  and one RCTadded comparing PTA plus stenting versus PTA alone. The review found improved patency rates on duplex ultrasound scans and angiography with PTA plus stenting at 6 months compared with PTA alone but no significant difference at 1 or 2 years. It also found that PTA plus stenting increased walking distance at 6 and 12 months but not at 24 months. The review found no significant difference between groups in ankle brachial index, quality of life, and adverse effects. The RCT compared PTA plus routine stenting versus PTA plus selective stenting. It found that PTA plus routine stenting reduced restenosis at 3, 6, and 12 months and increased patient-reported maximum walking distance at 6 and 12 months. Categorisation unchanged (Likely to be beneficial).
Cilostazol One systematic review  and one RCTadded both comparing cilostazol versus placebo. The review found cilostazol reduced all vascular and cerebrovascular events compared with placebo; however, it found no significant difference in cardiac events or serious bleeding episodes. The RCT found cilostazol improved claudication distances at 6 weeks, although there was no significant difference at 24 weeks. The RCT also found no significant difference between groups in ankle brachial index or quality-of-life scores at 24 weeks and reported more people withdrawing and reporting medication-related adverse effects at 24 weeks in the cilostazol group; however, the overall significance was not reported. Categorisation unchanged (Likely to be beneficial).
Prostaglandins Two systematic reviews added. The first review found that prostaglandins increased maximal walking distance and pain-free walking distance compared with both placebo and with pentoxifylline in people with intermittent claudication. The second review found no significant difference between prostaglandins and placebo in ulcer healing, amputations, rest pain relief, or reduction in analgesic consumption, although prostaglandins were associated with more adverse effects. Categorisation unchanged (Trade off between benefits and harms).
Pentoxifylline One systematic review added, which reported on both pentoxifylline versus placebo and pentoxifylline versus cilostazol.. The review found pentoxifylline increased maximal walking distance compared with placebo. For the pentoxifylline versus cilostazol comparison, the review identified only one RCT, which we already report in this Clinical Evidence review. Categorisation unchanged (Unknown effectiveness).