Canadian Cardiovascular Society 2022 Guidelines for Peripheral Arterial Disease.

Patients with widespread atherosclerosis such as peripheral artery disease (PAD) have a high risk of cardiovascular and limb symptoms and complications, which affects their quality of life and longevity. Over the past 2 decades there have been substantial advances in diagnostics, pharmacotherapy, and interventions including endovascular and open surgical to aid in the management of PAD patients. To summarize the evidence regarding approaches to diagnosis, risk stratification, medical and intervention treatments for patients with PAD, guided by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework, evidence was synthesized, and assessed for quality, and recommendations provided-categorized as weak or strong for each prespecified research question. Fifty-six recommendations were made, with 27% (15/56) graded as strong recommendations with high-quality evidence, 14% (8/56) were designated as strong recommendations with moderate-quality evidence, and 20% (11/56) were strong recommendations with low quality of evidence. Conversely 39% (22/56) were classified as weak recommendations. For PAD patients, strong recommendations on the basis of high-quality evidence, include smoking cessation interventions, structured exercise programs for claudication, lipid-modifying therapy, antithrombotic therapy with a single antiplatelet agent or dual pathway inhibition with low-dose rivaroxaban and aspirin; treatment of hypertension with an angiotensin converting enzyme or angiotensin receptor blocker; and for those with diabetes, a sodium-glucose cotransporter 2 inhibitor should be considered. Furthermore, autogenous grafts are more effective than prosthetic grafts for surgical bypasses for claudication or chronic limb-threatening ischemia involving the popliteal or distal arteries. Other recommendations indicated that new endovascular techniques and hybrid procedures be considered in patients with favourable anatomy and patient factors, and finally, the evidence for perioperative risk stratification for PAD patients who undergo surgery remains weak.

The effects of dietary flaxseed on cardiac arrhythmias and claudication in patients with peripheral arterial disease 1.

Patients with peripheral artery disease (PAD) are at increased risk for cardiovascular events, and higher susceptibility for cardiac arrhythmias may be involved. The objectives of this double-blinded randomized controlled FLAX-PAD trial were to determine whether daily consumption of a diet supplemented with 30 g of milled flaxseed (or placebo) over 1 year by PAD patients has effects on the prevalence of cardiac arrhythmias and exercise capacity. Cardiac arrhythmias were assessed on a cardiac stress test and at rest. At baseline, the PAD patients had a high incidence of cardiac arrhythmias (48% in the flaxseed group and 32% in the placebo group). After 1 year, the presence of cardiac arrhythmias in the flaxseed group decreased by 2% and increased by 12% in the placebo group (P > 0.05). Electrocardiographic variables (P, PR, QRS, QT, and QTc) did not change in either group during the trial. Patients from both groups improved initial and absolute claudication distances but the intergroup difference was also not statistically significant. In summary, the prevalence of cardiac arrhythmias and physical capacity trended in a positive direction for patients ingesting flaxseed but either a larger sample size or a longer intervention with flaxseed may be required to show statistically significant differences.

Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial.

BACKGROUND: Curcumin, a popular herbal supplement from the plant turmeric, has prevented ischemic reperfusion and toxin-induced injury in many animal studies and a single-centre randomized human trial. We sought to test whether perioperative oral curcumin (compared with placebo) affects the inflammatory response and risk of postrepair complications after elective abdominal aortic aneurysm repair in humans. METHODS: We conducted a parallel-group, randomized, placebo-controlled trial of patients from 10 hospitals in Canada who were scheduled to undergo elective repair of an unruptured abdominal aortic aneurysm (November 2011 to November 2014). Patients in the treatment group received perioperative oral curcumin (2000-mg doses 8 times over 4 d). Patients, health care providers and local research staff were unaware of the treatment assignment. The primary outcomes were median concentrations of 4 bio markers indicating injury and inflammation (postoperative urine interleukin-18 and perioperative rise in serum creatinine, plasma N-terminal pro-B-type natriuretic peptide and plasma high-sensitivity C-reactive protein). RESULTS: Baseline characteristics were similar in the 2 groups (606 patients overall; median age 76 yr). More than 85% of patients in each group took more than 80% of their scheduled capsules. Neither curcumin nor placebo significantly affected any of the 4 biomarkers (p > 0.05 for all comparisons). Regarding the secondary outcomes, there was a higher risk of acute kidney injury with curcumin than with placebo (17% v. 10%, p = 0.01), but no between-group difference in the median length of hospital stay (5 v. 5 days, p > 0.9) or the risk of clinical events (9% v. 9%, p = 0.9). INTERPRETATION: Curcumin had no beneficial effects when used in elective abdominal aortic aneurysm repair. These findings emphasize the importance of testing turmeric and curcumin before espousing their health benefits, as is currently done in the popular media. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01225094.

Feasibility and Tolerability of Daily Pulse Consumption in Individuals with Peripheral Artery Disease.

The present study investigated the feasibility, tolerability, and adherence of daily consumption of whole pulses (dried beans, peas, lentils, chickpeas) by individuals with peripheral artery disease participating in an 8-week study. Study questionnaires and semi-structured interviews for 26 participants were used to determine prestudy pulse consumption and participants' experiences with respect to adherence, positive and negative effects, bowel routine, satiety, and enjoyment of the foods. Although the majority of participants rarely consumed pulses prior to the study, there was a high rate of adherence to daily consumption of the study foods for 8 weeks despite comments regarding study fatigue during the latter part of the study. Participants had no gastrointestinal side effects (42%) or experienced flatulence that resolved by week 4 (23%), whereas 62% reported improvements in their bowel pattern. By week 8 greater satiety was noted by some participants (19%), with the categories "less afternoon snacking" and "not snacking" receiving more responses. The key finding of this study was that consumption of pulses is a viable approach for this population; however, the frequency of consumption that is tolerable in the long term should be integrated with the dose and timeframe required to achieve and maintain health benefits.

The ROVT Elan Valved Biplex Conduits for the Reconstruction of the Right Ventricular Outflow Tract.

The reconstruction of the right ventricular outflow tract (RVOT) system represents a considerable challenge for both manufacturers and surgeons because the patients requiring this type of devices have a very diverse set of anatomical challenges that can lead to complications and subsequent early device failures. We conducted an indepth investigation of a porcine-valve conduit explanted from a patient following an adverse event. A control device was analyzed as a reference. The rapid aging of the porcine valve in the right side of the heart together with major thrombus formation raises several questions. The difficulties encountered with materials used and also the design features of the conduits are once again highlighted. This group of patients continues to increase in number due to success in the surgical outcomes in early childhood. Therefore, there is a greater demand for an appropriate device. However, much work is still needed to achieve this goal, and the best approach to achieving success remains unanswered.

The Triplex BioValsalva Prostheses To Reconstruct the Aortic Valve and the Aortic Root.

The Bentall procedure introduced in 1968 represents an undisputed cure to treat multiple pathologies involving the aortic valve and the ascending thoracic aorta. Over the years, multiple modifications have been introduced as well as a standardized approach to the operation with the goal to prevent long-term adverse events. The BioValsalva prosthesis provides a novel manner to more efficiently reconstruct the aortic valve together with the anatomy of the aortic root with the implantation of a valved conduit. This prosthesis comprises three sections: the collar supporting the valve; the skirt mimicking the Valsalva, which is suitable for the anastomoses with the coronary arteries; and the main body of the graft, which is designed to replace the ascending aorta. The BioValsalva prosthesis allows the Bentall operation to be used in patients whose aortic valve cannot be spared.

Dietary Flaxseed Reduces Central Aortic Blood Pressure Without Cardiac Involvement but Through Changes in Plasma Oxylipins.

UNLABELLED: In the year-long FlaxPAD clinical trial (Flaxseed for Peripheral Artery Disease), dietary flaxseed generated a powerful reduction in brachial systolic and diastolic blood pressure in patients with peripheral artery disease. Oxylipins were implicated as potential mechanistic mediators. However, the ability of flaxseed to impact central aortic hypertension, arterial stiffness, or cardiac performance was not investigated. Additionally, the relationship between central blood pressure (cBP) and oxylipins was not elucidated. Therefore, radial tonometry and pulse wave analysis were used to measure cBP and cardiac function in the FlaxPAD population (n=62). Plasma oxylipins were analyzed with high-performance liquid chromatography mass spectrometry. In patients with high blood pressure at baseline, the average decrease in central systolic and diastolic blood pressures versus placebo was 10 and 6 mm Hg, respectively. Flaxseed did not significantly impact augmentation index or other cardiac function indices. Alternatively, the data support several specific oxylipins as potential mediators in the antihypertensive properties of flaxseed. For example, every 1 nmol/L increase in plasma 16-hydroxyeicosatetraenoic acid increased the odds of higher central systolic and diastolic blood pressures by 12- and 9-fold, respectively. Every 1 nmol/L increase in plasma thromboxane B2 and 5,6-dihydroxyeicosatrienoic acid increased the odds of higher cBP by 33- and 9-fold, respectively. Flaxseed induced a decrease in many oxylipins, which corresponded with a reduced risk of elevated cBP. These data extend the antihypertensive properties of flaxseed to cBP without cardiac involvement but rather through oxylipins. This study provides further support for oxylipins as therapeutic targets in hypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00781950.

Reframing tobacco dependency management in acute care: A case study.

Effective tobacco dependence treatment within acute care tends to be inadequate. The purpose of the Utilizing best practices to Manage Acute care patients Tobacco Dependency (UMAT) was to implement and evaluate an evidence-based intervention to support healthcare staff to effectively manage nicotine withdrawal symptoms of acute surgical patients. Data collection for this one-year longitudinal case study included: relevant patient experiences and staff reported practice, medication usage, and chart review. Over the year each data source suggested changes in tobacco dependence treatment. Key changes in patient survey responses (N=55) included a decrease in daily smoking and cigarette cravings. Of patients who used nicotine replacement therapy, they reported an increase in symptom relief. Staff (N=45) were surveyed at baseline, mid-point and end of study. Reported rates of assessing smoking status did not change over the year, but assessment of withdrawal symptoms emerged as daily practice and questions about cessation diminished. Also delivery of nicotine replacement therapy products increased over the year. Chart reviews showed a shift in content from documenting smoking behavior to withdrawal symptoms and administration of nicotine replacements; also frequency of comments increased. In summary, the evidence-based intervention influenced unit norms and reframed the culture related to tobacco dependence treatment.

Whole Soy Flour Incorporated into a Muffin and Consumed at 2 Doses of Soy Protein Does Not Lower LDL Cholesterol in a Randomized, Double-Blind Controlled Trial of Hypercholesterolemic Adults.

BACKGROUND: Soy protein may reduce coronary heart disease (CHD) risk by lowering LDL cholesterol, but few studies have assessed whether whole soy flour displays a similar effect. OBJECTIVE: The aim of this study was to assess the dose effect of whole soy flour incorporated into muffins on plasma LDL cholesterol in hypercholesterolemic adults. METHODS: Adults aged 30-70 y (n = 243) with elevated LDL cholesterol (≥3.0 and ≤5.0 mmol/L) were stratified by LDL cholesterol and randomly assigned to consume 2 soy muffins containing 25 g soy protein [high-dose soy (HDS)], 1 soy and 1 wheat muffin containing 12.5 g soy protein and 12.5 g whey protein [low-dose soy (LDS)], or 2 wheat muffins containing 25 g whey protein (control) daily for 6 wk while consuming a self-selected diet. Fasting blood samples were collected at weeks 0, 3, and 6 for analysis of plasma lipids [total, LDL, and HDL cholesterol and triglycerides (TGs)], glucose, insulin, C-reactive protein (CRP), and isoflavones. Blood pressures also were measured. Dietary intake was assessed at weeks 0 and 4 with the use of 3 d food records. Treatment effects were assessed with the use of intention-to-treat analysis with multiple imputation and LDL cholesterol as the primary outcome. RESULTS: In total, 213 (87.6%) participants completed the trial. Participants were primarily Caucasian (83%) and mostly female (63%), with a mean ± SD body mass index (in kg/m2) of 28.0 ± 4.6 and systolic and diastolic blood pressures of 122 ± 16 and 77 ± 11 mm Hg, respectively. Despite a dose-dependent increase in plasma isoflavones (P < 0.001), neither HDS nor LDS had a significant effect on LDL cholesterol compared with control (mean ± SEM changes: control, -0.04 ± 0.05 mmol/L; HDS, 0.01 ± 0.05 mmol/L; and LDS, -0.04 ± 0.06 mmol/L). There were no significant treatment effects on total or HDL cholesterol, TGs, CRP, homeostatic model assessment of insulin resistance, blood pressure, or the Framingham 10-y CHD risk score. CONCLUSION: Consuming 12.5 or 25 g protein from defatted soy flour incorporated into muffins does not reduce LDL cholesterol or other CHD risk factors in hypercholesterolemic adults. This trial was registered at clinicaltrials.gov as NCT01547585.

Dietary flaxseed independently lowers circulating cholesterol and lowers it beyond the effects of cholesterol-lowering medications alone in patients with peripheral artery disease.

BACKGROUND: Dietary flaxseed lowers cholesterol in healthy subjects with mild biomarkers of cardiovascular disease (CVD). OBJECTIVE: The aim was to investigate the effects of dietary flaxseed on plasma cholesterol in a patient population with clinically significant CVD and in those administered cholesterol-lowering medications (CLMs), primarily statins. METHODS: This double-blind, randomized, placebo-controlled trial examined the effects of a diet supplemented for 12 mo with foods that contained either 30 g of milled flaxseed [milled flaxseed treatment (FX) group; n = 58] or 30 g of whole wheat [placebo (PL) group; n = 52] in a patient population with peripheral artery disease (PAD). Plasma lipids were measured at 0, 1, 6, and 12 mo. RESULTS: Dietary flaxseed in PAD patients resulted in a 15% reduction in circulating LDL cholesterol as early as 1 mo into the trial (P = 0.05). The concentration in the FX group (2.1 ± 0.10 mmol/L) tended to be less than in the PL group (2.5 ± 0.2 mmol/L) at 6 mo (P = 0.12), but not at 12 mo (P = 0.33). Total cholesterol also tended to be lower in the FX group than in the PL group at 1 mo (11%, P = 0.05) and 6 mo (11%, P = 0.07), but not at 12 mo (P = 0.24). In a subgroup of patients taking flaxseed and CLM (n = 36), LDL-cholesterol concentrations were lowered by 8.5% ± 3.0% compared with baseline after 12 mo. This differed from the PL + CLM subgroup (n = 26), which increased by 3.0% ± 4.4% (P = 0.030) to a final concentration of 2.2 ± 0.1 mmol/L. CONCLUSIONS: Milled flaxseed lowers total and LDL cholesterol in patients with PAD and has additional LDL-cholesterol-lowering capabilities when used in conjunction with CLMs. This trial was registered at clinicaltrials.gov as NCT00781950.

A Floating Thrombus Anchored at the Proximal Anastomosis of a Woven Thoracic Graft Mimicking a Genuine Aortic Dissection.

An aortoesophageal fistula following surgery for a ruptured 6.6-cm thoracic aneurysm in a 69-year-old female was repaired using a 34-mm woven prosthetic graft. A follow-up computed tomography (CT) scan at 10 days postoperatively revealed a dissection-like picture in the region of the graft, which was treated conservatively. The patient eventually died from sepsis and multiorgan failure. At autopsy, the graft was retrieved in situ and studied by detailed gross, microscopy, and scanning electron microscopy (SEM) examination. Gross observation confirmed that the dissection resulted from the rolling of the internal capsule downstream. A massive thrombus anchored at the proximal anastomosis and held by a narrow head was also noted. The thrombus demonstrated reorganization in the area of the anastomosis, with a false lumen in its distal half. The reminder of the thrombus consisted of layered fibrin. After gross examination, the fabric graft was found to be flawless. Additional detailed studies were also done using microscopy, SEM, and gross examination.

Female sex does not influence 30-day stroke and mortality rates after carotid endarterectomy.

BACKGROUND: Sex-based differences in outcomes for the treatment of carotid arterial disease remains a controversial topic. The main objective of this study was to determine if gender differences influence 30-day stroke and mortality rates after carotid endarterectomy (CEA) in a large series of patients. METHODS: This is a retrospective study of all patients undergoing endarterectomy performed by a single surgeon between January 1, 1993 and December 15, 2010. The analysis included data from 1,046 CEAs (683 men and 363 women). RESULTS: There were no differences found in 30-day stroke, death, or combined stroke and death rates between women and men. The 30-day stroke rate was 1.6% for women and 1.8% for men (P = 0.98), with no significant differences between asymptomatic patients (1.7% for women vs. 1.2% for men; P = 0.70) or symptomatic patients (1.6% for women vs. 2.1% for men; P = 0.74). The 30-day mortality rate was 0.8% for women and 0.9% for men (P = 0.85) with no significant differences between asymptomatic patients (0.8% for women vs. 1.2% for men; P = 0.77) and symptomatic patients (0.8% for women vs. 0.7% for men; P = 0.84). There was a similar low risk for the combined outcome of stroke and death (1.9% for women vs. 2.2% for men; P = 0.92), with no differences between asymptomatic patients (1.7% for women vs. 1.6% for men; P = 0.89) or symptomatic patients (2.1% for women vs. 2.5% for men; P = 0.84). CONCLUSIONS: Female sex does not influence 30-day stroke and mortality rates after CEA, regardless of preoperative symptom status.

Daily non-soy legume consumption reverses vascular impairment due to peripheral artery disease.

OBJECTIVE: Peripheral artery disease (PAD) results from a decrease in blood flow to the limbs due to the presence of atherosclerotic plaque. It has been reported that isoflavones isolated from soybeans reduce arterial stiffness, a component of atherosclerotic disease. This study examined the effect of consuming whole legumes (non-soy) on arterial function in humans with PAD. METHODS: Twenty-six individuals with PAD consumed ½ cup/day cooked legumes (beans, peas, lentils, chickpeas) daily for 8 weeks. Measurements of circulating factors and vascular function at baseline and study conclusion were compared. RESULTS: No changes in were detected relative to baseline values for most parameters. Total and LDL-cholesterol were reduced by 5.0% and 8.7%, respectively. The ankle-brachial index (ABI) showed a 5.5% increase. Changes in ABI and LDL-cholesterol did not correlate. Serum markers of endothelial dysfunction and inflammation were unchanged, but short-chain acylcarnitine concentrations were significantly decreased. CONCLUSIONS: A legume-rich diet can elicit major improvements in arterial function and serum cholesterol in the absence of changes in either body mass or blood pressure, although the improvements in vascular function and serum lipids were unrelated. Although the positive results obtained with this dietary intervention were not explained by biomarkers of endothelial function and inflammation, altered acylcarnitine levels indicate an improvement in skeletal muscle metabolism due to enhanced tissue perfusion.

Potent antihypertensive action of dietary flaxseed in hypertensive patients.

Flaxseed contains ω-3 fatty acids, lignans, and fiber that together may provide benefits to patients with cardiovascular disease. Animal work identified that patients with peripheral artery disease may particularly benefit from dietary supplementation with flaxseed. Hypertension is commonly associated with peripheral artery disease. The purpose of the study was to examine the effects of daily ingestion of flaxseed on systolic (SBP) and diastolic blood pressure (DBP) in peripheral artery disease patients. In this prospective, double-blinded, placebo-controlled, randomized trial, patients (110 in total) ingested a variety of foods that contained 30 g of milled flaxseed or placebo each day over 6 months. Plasma levels of the ω-3 fatty acid α-linolenic acid and enterolignans increased 2- to 50-fold in the flaxseed-fed group but did not increase significantly in the placebo group. Patient body weights were not significantly different between the 2 groups at any time. SBP was ≈ 10 mm Hg lower, and DBP was ≈ 7 mm Hg lower in the flaxseed group compared with placebo after 6 months. Patients who entered the trial with a SBP ≥ 140 mm Hg at baseline obtained a significant reduction of 15 mm Hg in SBP and 7 mm Hg in DBP from flaxseed ingestion. The antihypertensive effect was achieved selectively in hypertensive patients. Circulating α-linolenic acid levels correlated with SBP and DBP, and lignan levels correlated with changes in DBP. In summary, flaxseed induced one of the most potent antihypertensive effects achieved by a dietary intervention.

A comparative study of bovine and porcine pericardium to highlight their potential advantages to manufacture percutaneous cardiovascular implants.

RATIONALE: Prosthetic heart valves designed to be implanted percutaneously must be loaded within delivery catheters whose diameter can be as low as 18 F (6 mm). This mandatory crimping of the devices may result in deleterious damages to the tissues used for valve manufacturing. As bovine and porcine pericardial tissue are currently given preference because of their excellent availability and traceability, a preliminary comparative study was undertaken to highlight their potential advantages. MATERIALS AND METHODS: Bovine and pericardium patches were compared morphologically (light microscopy, scanning electron microscopy and transmission electron microscopy). The acute thrombogenicity of both materials was measured in term of platelet uptake and observed by scanning electron microscopy, porcine intact and injured arteries being used as controls. The pericardium specimens were also subjected to uniaxial tensile tests to compare their respective mechanical characteristics. RESULTS: Both pericardiums showed a layered architecture of collagen bundles presenting some interstitial cells. They displayed wavy crimps typical of an unloaded collagenous tissue. The collagen bundles were not bound together and the fibrils were parallel with characteristic periodicity patterns of cross striations. The mesothelial cells found in vivo on the serous surface were no longer present due to tissue processing, but the adjacent structure was far more compacted when compared to the fibrous side. The fibrinocollagenous surfaces were found to be more thrombogenic for both bovine and porcine tissues and the serous side of the porcine pericardium retained more platelets when compared to the bovine samples, making the acute thrombogenicity more important in the porcine pericardium. CONCLUSION: Both bovine and porcine pericardium used in cardiovascular implantology can be selected to manufacture percutaneous heart valves. The selection of one pericardium preferably to the other should deserve additional testing regarding the innocuousness of crimping when loaded in delivery catheters and the long-term durability after percutaneous deployment.

Incisional hernia postrepair of abdominal aortic occlusive and aneurysmal disease: five-year incidence.

The aim of this study was to report the five-year incidence of incisional hernia after vascular repair of abdominal aortic occlusive (AOD) and aneurysmal disease (AAA), and to determine the factors associated with the development of this complication. Consecutive patients who underwent AAA and AOD at the University of Manitoba, Canada, between January 1999 and December 2002, were recruited and evaluated by clinical examination one week, one month and six months after the surgery, and through medical records review thereafter. The development of postoperative incisional hernia was recorded and analyzed. Two-hundred four patients, with a mean age of 70.1 years, provided consent for the study. The overall five-year incidence of incisional hernia was 69.1% and the overall median failure time was 48 months. The median failure time was 48 months for AOD and 36 months for AAA (P < 0.01). The urgent and ruptured AAA repair had a higher five-year incidence of incisional hernia as compared with AOD or elective AAA repair (P < 0.01). A history of bilateral inguinal hernia was significantly associated with incisional hernia (P < 0.05). Men and patients who were 65 years and older had a higher five-year incidence of incisional hernia (P < 0.01). Age ≥65 years, male gender, hypertension and past bilateral inguinal hernia repair double the risk for the development of incisional hernia (hazard ratio = 2.1. 2.2, 1.7 and 2.8, respectively). In conclusion, the five-year incidence of incisional hernia after vascular repair of AOD or AAA is 69.1%, and tends to occur late after vascular repair.

Antithrombotic therapy in peripheral artery disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND: This guideline focuses on antithrombotic drug therapies for primary and secondary prevention of cardiovascular disease as well as for the relief of lower-extremity symptoms and critical ischemia in persons with peripheral arterial disease (PAD). METHODS: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS: The most important of our 20 recommendations are as follows. In patients aged ≥ 50 years with asymptomatic PAD or asymptomatic carotid stenosis, we suggest aspirin (75-100 mg/d) over no therapy (Grade 2B) for the primary prevention of cardiovascular events. For secondary prevention of cardiovascular disease in patients with symptomatic PAD (including patients before and after peripheral arterial bypass surgery or percutaneous transluminal angioplasty), we recommend long-term aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 1A). We recommend against the use of warfarin plus aspirin in patients with symptomatic PAD (Grade 1B). For patients undergoing peripheral artery percutaneous transluminal angioplasty with stenting, we suggest single rather than dual antiplatelet therapy (Grade 2C). For patients with refractory claudication despite exercise therapy and smoking cessation, we suggest addition of cilostazol (100 mg bid) to aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 2C). In patients with critical limb ischemia and rest pain unable to undergo revascularization, we suggest the use of prostanoids (Grade 2C). In patients with acute limb ischemia due to acute thrombosis or embolism, we recommend surgery over peripheral arterial thrombolysis (Grade 1B). CONCLUSIONS: Recommendations continue to favor single antiplatelet therapy for primary and secondary prevention of cardiovascular events in most patients with asymptomatic PAD, symptomatic PAD, and asymptomatic carotid stenosis. Additional therapies for relief of limb symptoms should be considered only after exercise therapy, smoking cessation, and evaluation for peripheral artery revascularization.