Gillian C Leng

Aspirin for Prevention of Cardiovascular Events in a General Population Screened for a Low Ankle Brachial Index: A Randomized Controlled Trial

CONTEXTnA low ankle brachial index (ABI) indicates atherosclerosis and an increased risk of cardiovascular and cerebrovascular events. Screening for a low ABI can identify an asymptomatic higher risk group potentially amenable to preventive treatments.nnnOBJECTIVEnTo determine the effectiveness of aspirin in preventing events in people with a low ABI identified on screening the general population.nnnDESIGN, SETTING, AND PARTICIPANTSnThe Aspirin for Asymptomatic Atherosclerosis trial was an intention-to-treat double-blind randomized controlled trial conducted from April 1998 to October 2008, involving 28,980 men and women aged 50 to 75 years living in central Scotland, free of clinical cardiovascular disease, recruited from a community health registry, and had an ABI screening test. Of those, 3350 with a low ABI (< or = 0.95) were entered into the trial, which was powered to detect a 25% proportional risk reduction in events.nnnINTERVENTIONSnOnce daily 100 mg aspirin (enteric coated) or placebo.nnnMAIN OUTCOME MEASURESnThe primary end point was a composite of initial fatal or nonfatal coronary event or stroke or revascularization. Two secondary end points were (1) all initial vascular events defined as a composite of a primary end point event or angina, intermittent claudication, or transient ischemic attack; and (2) all-cause mortality.nnnRESULTSnAfter a mean (SD) follow-up of 8.2 (1.6) years, 357 participants had a primary end point event (13.5 per 1000 person-years, 95% confidence interval [CI], 12.2-15.0). No statistically significant difference was found between groups (13.7 events per 1000 person-years in the aspirin group vs 13.3 in the placebo group; hazard ratio [HR], 1.03; 95% CI, 0.84-1.27). A vascular event comprising the secondary end point occurred in 578 participants (22.8 per 1000 person-years; 95% CI, 21.0-24.8) and no statistically significant difference between groups (22.8 events per 1000 person-years in the aspirin group vs 22.9 in the placebo group; HR, 1.00; 95% CI, 0.85-1.17). There was no significant difference in all-cause mortality between groups (176 vs 186 deaths, respectively; HR, 0.95; 95% CI, 0.77-1.16). An initial event of major hemorrhage requiring admission to hospital occurred in 34 participants (2.5 per 1000 person-years) in the aspirin group and 20 (1.5 per 1000 person-years) in the placebo group (HR, 1.71; 95% CI, 0.99-2.97).nnnCONCLUSIONnAmong participants without clinical cardiovascular disease, identified with a low ABI based on screening a general population, the administration of aspirin compared with placebo did not result in a significant reduction in vascular events.nnnTRIAL REGISTRATIONnisrctn.org Identifier: ISRCTN66587262.

Bypass surgery for chronic lower limb ischaemia

BACKGROUNDnSurgical bypass of an occluded arterial segment is one of the mainstay treatments for patients with critical limb ischaemia (CLI). However, it was introduced without formal evaluation.nnnOBJECTIVESnTo determine the effects of bypass surgery in patients with CLI.nnnSEARCH STRATEGYnThe Cochrane Peripheral Vascular Diseases Group (PVD) searched their trials register (last searched November 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (last searched Issue 4, 2007). Principal trial investigators were also contacted.nnnSELECTION CRITERIAnAll randomised controlled trials (RCTs) of bypass surgery versus control or any other treatment.nnnDATA COLLECTION AND ANALYSISnFor the update one author and PVD editorial staff extracted data and assessed trial quality. Unpublished data were obtained from trial investigators. Data were analyzed using Peto odds ratio (OR) or weighted mean difference (fixed and random effects models).nnnMAIN RESULTSnNineteen trials were identified. Eight involved a total of just over 1200 patients. Four trials compared bypass surgery with angioplasty (PTA) and one each with thromboendarterectomy, thrombolysis, exercise, and spinal cord stimulation. Four included patients with intermittent claudication (IC) and CLI, two were restricted to claudicants, and two to CLI. Vein grafts were used for distal reconstructions and synthetic prostheses for aorto-iliac or ilio-femoral bypasses. Six trials included mortality. In general, trial quality was good; blinding was not possible. Mortality and amputation rates did not differ significantly between bypass surgery and PTA; primary patency was significantly higher in the bypass group after 12 months (Peto OR 1.6, 95% CI 1.0 to 2.6) but not after four years (P = 0.14). In patients with lower CLI, surgery was associated with increased surgical complications (Peto OR 2.69, 95% CI 1.87 to 3.86) and longer hospital stays during the first year, mean stay 46.1 days (SD 53.9) compared with 36.4 days (SD 51.4) for those receiving PTA (P < 0.0001). Amputation rates were significantly lower in bypass compared with thrombolysis (Peto OR 0.2, 95% CI 0.1 to 0.6); mortality rates did not differ. Blood flow restoration was significantly greater in bypass than in thromboendarterectomy patients (Peto OR 9.2, 95% CI 1.7 to 50.6); mortality and amputation rates did not differ. Bypass surgery outcomes did not differ significantly from exercise or spinal cord stimulation.nnnAUTHORS CONCLUSIONSnThere is limited evidence for the effectiveness of bypass surgery compared with other treatments; no studies compared bypass to no treatment. Further large trials are required.

Lipid‐lowering for lower limb atherosclerosis

BACKGROUNDnRaised lipid levels, including cholesterol, are important risk factors in the development of lower limb arterial disease (atherosclerosis).nnnOBJECTIVESnThe objective of this review was to assess the effects of lipid lowering therapy in patients with lower limb atherosclerosis.nnnSEARCH STRATEGYnThe reviewers searched the Cochrane Peripheral Vascular Diseases Group trials register, Embase, reference lists of relevant articles, and contacted trial investigators in Europe and pharmaceutical companies.nnnSELECTION CRITERIAnRandomised trials of lipid-lowering therapy in patients with lower limb atherosclerosis. The main outcomes were mortality, non-fatal events, direct tests of disease progression, indirect measurements of disease, and subjective measures.nnnDATA COLLECTION AND ANALYSISnTwo reviewers extracted data and assessed trial quality independently. The reviewers contacted investigators to obtain information needed for the review that could not be found in published reports.nnnMAIN RESULTSnThere were nine eligible trials, but two were excluded because of poor methodology. The seven remaining trials involved a total of 698 participants from seven different countries. Men and women participated in all but one trial and were generally middle aged to elderly. The follow-up period varied from four months to three years. The overall quality of the included trials was high. The trials were heterogeneous in terms of inclusion criteria, type of drugs used and outcomes measured. Lipid-lowering therapy produced a marked but non-significant reduction in mortality (odds ratio 0.21, 95% confidence interval 0. 03 to 1.17), but little change in non-fatal events (odds ratio 1.21, 95% confidence interval 0.80 to 1.83). In two trials there was a significant overall reduction in disease progression on angiogram (odds ratio 0.47, 95% confidence interval 0.29 to 0.77). The changes in ankle brachial pressure index and walking distance were inconsistent, although trials showed a general improvement in symptoms that could not be combined in a meta-analysis. Side effects were generally mild, with the exceptions of liver toxicity produced by betapyridil and the adverse effect of probucol on lipoprotein profile.nnnREVIEWERS CONCLUSIONSnLipid-lowering therapy may be useful in preventing deterioration of underlying disease and alleviating symptoms. These results cannot determine whether one lipid-lowering regimen is better than another.

Garlic for peripheral arterial occlusive disease

BACKGROUNDnCommercially available preparations of garlic have been reported to have beneficial effects on some of the risk factors associated with atherosclerosis.nnnOBJECTIVESnTo assess the effects of garlic (both dried and non-powdered preparations) for the treatment of peripheral arterial occlusive disease.nnnSEARCH METHODSnFor this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2013) and CENTRAL (2012, Issue 12).nnnSELECTION CRITERIAnRandomised trials of garlic therapy in patients with lower limb atherosclerosis were included. The main outcomes were objective measures of progression of underlying atherosclerosis (e.g. ankle pressure measurements, treadmill testing) and subjective measures (e.g. symptom progression).nnnDATA COLLECTION AND ANALYSISnTwo review authors (RJ and JK) independently extracted data and assessed trial quality. One author (RJ) contacted investigators to obtain information needed for the review that could not be found in published reports.nnnMAIN RESULTSnOne eligible trial with 78 participants was found. Both men and women (aged 40 to 75) were included. The follow-up period was short, 12 weeks only.After twelve weeks of treatment, pain-free walking distance increased from 161 to 207 metres in the group receiving garlic and from 172 to 203 metres in the placebo group. This was not a statistically significant difference. There was no difference in change of systolic or diastolic blood pressure, heart rate, ankle and brachial pressures. No severe side effects were observed and nine patients taking garlic (28%) and four patients taking placebo (12%) complained of a noticeable garlic smell.Three trials were excluded from the review because they did not include any clinical measurements.nnnAUTHORS CONCLUSIONSnOne small trial of short duration found no statistically significant effect of garlic on walking distance.

Essential fatty acids and cardiovascular disease: the Edinburgh Artery Study.

The aim of this study was to determine whether plasma and red cell fatty acid levels were associated with cardiovascular disease, and whether any association was independent of other major risk factors. Over 1100 subjects were examined in a random sample survey of the general population (the Edinburgh Artery Study). Fatty acids were measured in three plasma fractions (triglyceride, cholesteryl ester and phospholipid) and in red cell phospholipids. Fatty acid levels in groups with cardiovascular disease (myocardial infarction (MI), angina and lower limb disease) were compared with a no disease group. In the cholesteryl ester and phospholipid fractions there were significantly lower levels of eicosapentaenoic acid in the MI group on univariate analysis (p,0.05), but not when adjusted for age, sex, smoking and systolic blood pressure using logistic regression. In the red cell fraction, alpha-linolenic acid was significantly lower in those with stroke (p,0.01) and lower limb disease (p,0.05). Linoleic acid was significantly raised in the triglyceride fraction in those with MI, probably reflecting recent dietary changes. There were significant increases in dihomo-gamma-linolenic acid in the phospholipid and red cell fractions in those with MI, and in the phospholipid fraction in the stroke group. These results do not support the hypothesis that n-6 fatty acids are protective against cardiovascular disease, although there may be some beneficial effects of the n-3 fatty acid, alpha-linolenic acid. Results from cross-sectional surveys must, however, be interpreted with caution because the presence of disease may affect dietary intake.

Steroid sex hormones for lower limb atherosclerosis.

BACKGROUNDnThere is accumulating evidence that steroid sex hormones have a beneficial effect on a number of risk factors for peripheral arterial disease.nnnOBJECTIVESnThe objective of this review was to determine whether exogenous steroid sex hormones are an effective treatment for patients with lower limb atherosclerosis.nnnSEARCH METHODSnFor this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched August 2012) and CENTRAL 2012, Issue 7. There were no language restrictions.nnnSELECTION CRITERIAnWe selected randomised or quasi-randomised controlled trials of steroid sex hormones in patients with lower limb atherosclerosis.nnnDATA COLLECTION AND ANALYSISnBoth authors extracted data and assessed trial quality independently. Whenever possible investigators were contacted to obtain information needed for the review that could not be found in published reports.nnnMAIN RESULTSnFour trials appeared to meet the inclusion criteria, but one was excluded because of poor methodology. The three remaining trials compared testosterone treatment with placebo in a total of 109 subjects with intermittent claudication or critical leg ischaemia. The most recent trial to meet the inclusion criteria dated from 1971. No trials were available which investigated the potentially beneficial effects of oestrogenic hormones in women with lower limb atherosclerosis.Testosterone therapy produced no significant improvement in tests of walking distance or in a variety of other objective tests for peripheral arterial disease, including venous filling time, muscle blood flow and plethysmography. The relative risk for subjective improvement in symptoms using the combined trial results was also non-significant (relative risk (RR) 1.10, 95% confidence interval (CI) 0.81 to 1.48).nnnAUTHORS CONCLUSIONSnThere is no evidence to date that short-term testosterone treatment is beneficial in subjects with lower limb atherosclerosis. However, this might reflect limited data rather than the lack of a real effect.

Garlic for peripheral arterial occlusive disease (Review)

BACKGROUNDnCommercially available preparations of garlic have been reported to have beneficial effects on some of the risk factors associated with atherosclerosis.nnnOBJECTIVESnThe objective of this review was to assess the effects of garlic (both dried and non-powdered preparations) for the treatment of peripheral arterial occlusive disease.nnnSEARCH STRATEGYnThe reviewers searched the Cochrane Peripheral Vascular Diseases Group trials register, AMED, EMBASE, BIDS ISI, abstracts of relevant symposia and reference lists of relevant articles up to August 1998. The reviewers also contacted pharmaceutical companies, investigators and experts in garlic therapies.nnnSELECTION CRITERIAnRandomised trials of garlic therapy in patients with lower limb atherosclerosis. The main outcomes were objective measures of progression of underlying atherosclerosis (e.g. ankle pressure measurements, treadmill testing) and subjective measures (e.g. symptom progression).nnnDATA COLLECTION AND ANALYSISnAt least two reviewers extracted data and assessed trial quality independently. The reviewers contacted investigators to obtain information needed for the review that could not be found in published reports.nnnMAIN RESULTSnOne eligible trial with 78 participants was found. Both men and women (aged 40-75) were included. The follow-up period was short, 12 weeks only. After twelve weeks of treatment, pain free walking distance increased from 161 to 207 m in the group on garlic and from 172 to 203 m in the placebo group. This was not a statistically significant difference. There was no difference in change of systolic or diastolic blood pressure, heart rate, ankle and brachial pressures. No severe side effects were observed and nine patients taking garlic (28%) and four patients taking placebo (12%) complained of a noticeable garlic smell.nnnREVIEWERS CONCLUSIONSnOne small trial of short duration found no effect on walking distance.