Antithrombotic Therapy After Peripheral Vascular Intervention

Cardioprotective medications and risk-factor modification are the hallmarks of treatment for all patients with peripheral artery disease (PAD). If symptoms are life-limiting and/or do not respond to conservative treatment, endovascular or surgical revascularization can be considered especially for patients with critical limb ischemia or acute limb ischemia. The rates of peripheral vascular intervention (PVI) have risen dramatically over the past few decades and much of this care have shifted from inpatient hospital settings to outpatient settings and office-based clinics. While PVI rates have surged and technology advancements have dramatically changed the face of PVI, the data behind optimal antithrombotic therapy following PVI is scant. Currently in the USA, most patients are treated with indefinite aspirin therapy and a variable duration of clopidogrel (or other P2Y12 inhibitor)—typically 1 month, 3 months, or indefinite therapy. More observational analyses and randomized clinical trials evaluating clinically relevant outcomes such as cardiovascular morbidity/mortality and the risk of bleeding are needed to guide the optimal role and duration of antithrombotic therapy post-PVI.     

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.     

Rivaroxaban Plus Aspirin Versus Aspirin in Relation to Vascular Risk in the COMPASS Trial

BackgroundThe COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial showed that the combination of low-dose rivaroxaban and aspirin reduced major vascular events in patients with stable vascular disease.ObjectivesThe purpose of this study was to identify subsets of patients at higher risk of recurrent vascular events, which may help focus the use of rivaroxaban and aspirin therapy.MethodsCOMPASS patients with vascular disease were risk stratified using 2 methods: the REACH (REduction of Atherothrombosis for Continued Health) atherothrombosis risk score and CART (Classification and Regression Tree) analysis. The absolute risk differences for rivaroxaban with aspirin were compared to aspirin alone over 30 months for the composite of cardiovascular death, myocardial infarction, stroke, acute limb ischemia, or vascular amputation; for severe bleeding; and for the net clinical benefit.ResultsHigh-risk patients using the REACH score were those with 2 or more vascular beds affected, history of heart failure (HF), or renal insufficiency, and by CART analysis were those with ≥2 vascular beds affected, history of HF, or diabetes. Rivaroxaban and aspirin combination reduced the serious vascular event incidence by 25% (4.48% vs. 5.95%, hazard ratio: 0.75; 95% confidence interval: 0.66 to 0.85), equivalent to 23 events prevented per 1,000 patients treated for 30 months, at the cost of a nonsignificant 34% increase in severe bleeding (1.34; 95% confidence interval: 0.95 to 1.88), or 2 events caused per 1,000 patients treated. Among patients with ≥1 high-risk feature identified from the CART analysis, rivaroxaban and aspirin prevented 33 serious vascular events, whereas in lower-risk patients, rivaroxaban and aspirin treatment led to the avoidance of 10 events per 1,000 patients treated for 30 months.ConclusionsIn patients with vascular disease, further risk stratification can identify higher-risk patients (≥2 vascular beds affected, HF, renal insufficiency, or diabetes). The net clinical benefit remains favorable for most patients treated with rivaroxaban and aspirin compared with aspirin.     

Triple Antithrombotic Therapy in Atrial Fibrillation Patients Undergoing PCI: a Fading Role

Triple antithrombotic therapy (TAT), consisting of aspirin, a P2Y₁₂ receptor antagonist and oral anticoagulant (OAC) medication has been considered as an ‘unavoidable’ strategy for a 1–12 months for atrial fibrillation (AF) patients post acute coronary syndrome or percutaneous coronary angioplasty with stenting. However, TAT has rather poorly been adopted in real life practice, mainly because of an accompanying increased bleeding potential and lack of definitive results of randomized clinical trials. Several registries, meta-analyses and small randomized trials have so far provided the base of guidelines recommendations. Furthermore, in the recently published Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects with Atrial Fibrillation who Undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial involving 2124 patients, the primary safety endpoint of clinically significant bleeding was significantly reduced in the rivaroxaban low dose (15 mg daily) plus single P2Y₁₂ receptor antagonist arm compared to TAT, with no difference in the secondary efficacy endpoint. Despite several limitations of the PIONEER AF-PCI trial, it appears that among patients who omit aspirin, there may be equivalent ischemic protection with dual therapy and no disadvantage for additional risk of thrombotic events.     

Advances in monitoring of aspirin therapy

The efficacy of aspirin to prevent thrombotic events in cardiovascular patients is well established, with >100 randomized trials having been conducted in high-risk patients and demonstrating a reduction in vascular death of approximately 15% and a further reduction in non-fatal vascular events of approximately 30%. While the benefit of aspirin is undisputed, it is also known that aspirin is associated with a dose-dependent increase in the risk of bleeding. It follows that most treatment guidelines advocate the use of the lowest aspirin dose effective in preventing thrombotic complications to minimize the risk of major bleeding. From this, a need for monitoring of aspirin therapy has emerged and prompted the development and investigation of numerous assays of platelet function. The intention behind monitoring of aspirin's antithrombotic effects is to maximize benefit and to personalize treatment based on individual patient characteristics. This article reviews the recent literature on the usefulness of platelet function testing in patients requiring aspirin; the variability of platelet reactivity in patients taking aspirin and its clinical impact; the potential mechanisms underlying suboptimal platelet inhibition by aspirin and future directions in terms of management of aspirin therapy.     

Evidence-Experience Gap and Future Perspective on the Treatment of Peripheral Artery Disease

Peripheral artery disease (PAD) is a systemic disease associated with impaired limb function, poor quality of life, and increased cardiovascular morbidity. Its incidence has been dramatically increasing over years because of the emergence of an aging society and the increase in the number of patients with atherosclerotic risk factors. The clustering of these risk factors promotes disease development, reportedly leading to the differential location of atherosclerotic lesions in lower extremity arteries. The clinical presentations of PAD include intermittent claudication and chronic limb-threatening ischemia (CLTI). PAD is associated with a high risk of mortality and morbidity from both cardiovascular and limb events. The therapeutic goals for patients with PAD include 1) relief from PAD-related limb symptoms, 2) the prevention of new-onset and the development and recurrence of PAD, and 3) the prevention of concomitant adverse events due to coronary artery disease (CAD) and cerebrovascular disease (CVD). There are several types of antithrombotic agents, and their main role in patients with PAD is to reduce systemic events mainly including cardiovascular and lower extremity-related events. Currently, the efficacy of direct oral anticoagulant (DOAC) is also suggested by recent clinical trials. Although endovascular therapy (EVT) has been a first-line revascularization strategy for symptomatic PAD, whether clinical outcomes after EVT are comparable to those after surgical bypass therapy remains inconclusive.     

Design and Rationale of the RE‐DUAL PCI Trial: A Prospective,Randomized, Phase 3b Study Comparing the Safety and Efficacy of Dual Antithrombotic Therapy With Dabigatran Etexilate Versus Warfarin Triple Therapy in Patients With Nonvalvular Atrial Fibrillation Who Have Undergone Percutaneous Coronary Intervention With Stenting

Antithrombotic management of patients with atrial fibrillation (AF) undergoing coronary stenting is complicated by the need for anticoagulant therapy for stroke prevention and dual antiplatelet therapy for prevention of stent thrombosis and coronary events. Triple antithrombotic therapy, typically comprising warfarin, aspirin, and clopidogrel, is associated with a high risk of bleeding. A modest‐sized trial of oral anticoagulation with warfarin and clopidogrel without aspirin showed improvements in both bleeding and thrombotic events compared with triple therapy, but large trials are lacking. The RE‐DUAL PCI trial (NCT 02164864) is a phase 3b, a strategy of prospective, randomized, open‐label, blinded‐endpoint trial. The main objective is to evaluate dual antithrombotic therapy with dabigatran etexilate (110 or 150 mg twice daily) and a P2Y12 inhibitor (either clopidogrel or ticagrelor) compared with triple antithrombotic therapy with warfarin, a P2Y12 inhibitor (either clopidogrel or ticagrelor, and low‐dose aspirin (for 1 or 3 months, depending on stent type) in nonvalvular AF patients who have undergone percutaneous coronary intervention with stenting. The primary endpoint is time to first International Society of Thrombosis and Hemostasis major bleeding event or clinically relevant nonmajor bleeding event. Secondary endpoints are the composite of all cause death or thrombotic events (myocardial infarction, or stroke/systemic embolism) and unplanned revascularization; death or thrombotic events; individual outcome events; death, myocardial infarction, or stroke; and unplanned revascularization. A hierarchical procedure for multiple testing will be used. The plan is to randomize ～ 2500 patients at approximately 550 centers worldwide to try to identify new treatment strategies for this patient population.     

Perioperative clinical variables and long-term survival following vascular surgery

Cardiovascular disease is the leading cause of death in patients with peripheral arterial disease(PAD). Coro-nary artery disease(CAD) is highly prevalent, and often times coexist, in patients with PAD. The management of patients with PAD that requires a high-risk vascular surgical procedure for intermittent claudication, critical limb ischemia or expanding abdominal aortic aneurysm requires risk stratification with the revised cardiac risk index, optimization of medical therapies, and limited use of cardiac imaging prior to surgery. Preventive re-vascularization in patients with stable CAD, with the sole intention to mitigate the risk of cardiac complica-tions in the peri-operative period, is not effective and may be associated with significant bleeding and throm-botic risks, in particular if stents are used. A strategy of universal use of cardiac troponins in the perioperative period for active surveillance of myocardial ischemia may be more reasonable and cost-effective than the current standard of care of widespread use of cardiac imaging prior to high-risk surgery. An elevated cardiactroponin after vascular surgery is predictive of long-term mortality risk. Medical therapies such as aspirin and statins are recommended for patients with post-operative myocardial ischemia. Ongoing trials are as-sessing the role of novel anticoagulants. Additional research is needed to define the role of cardiac imaging and invasive angiography in this population.     

Chronic Coronary Syndrome: Overcoming Clinical Practice Guidelines. The Role of the COMPASS Strategy

Current European guidelines on chronic coronary syndromes recommend the use of low-dose aspirin (or clopidogrel if intolerance or contraindication occurs) throughout life. However, as the risk of recurrent vascular events is high, particularly in some patients (i.e. diffuse multivessel coronary artery disease, diabetes, recurrent myocardial infarction, peripheral artery disease, or chronic kidney disease,…), these guidelines also consider that in those patients at moderate or high risk of ischemic events, but without a high bleeding risk, dual antithrombotic therapy should be considered. According to these guidelines, treatment options for dual antithrombotic therapy in combination with aspirin may include clopidogrel 75 mg/daily, prasugrel 10 mg/daily, ticagrelor 60 mg bid or rivaroxaban 2.5 mg bid. Remarkably, despite the results of the clinical trials that sustain these recommendations clearly diverge, guidelines do not differentiate between them. However, although all these drugs have demonstrated a significant reduction in major cardiovascular events in patients with stable atherosclerotic disease, only the addition of rivaroxaban has been associated with a reduction in cardiovascular and overall mortality in the secondary analysis. This may be related to the fact that the activation of platelets and factor X plays a key role in the development of atherothrombosis, and, consequently, both targets should be considered for the appropriate management of these patients.     

Prevention of gastrointestinal events in patients on antithrombotic therapy in the peri‐endoscopy period: Review of new evidence and recommendations from recent guidelines

Management of patients on antithrombotic therapy undergoing endoscopic procedures can be challenging. Although guidelines from major gastrointestinal endoscopy societies provide useful recommendations in this regard, data are limited concerning the bleeding risk of new complex endoscopic procedures and the management of novel anticoagulants in patients needing invasive procedures. The approach to the management of antithrombotic therapy often needs to be formulated on an individual basis, especially in patients with high thrombotic risk undergoing a high‐risk endoscopic procedure. In addition to the procedure‐related bleeding risk, endoscopists also need to consider the urgency of the endoscopic procedure, the thromboembolic risk of the patient if antithrombotic therapy is temporarily withheld, and the timing of discontinuation/resumption of antithrombotic therapy in the decision‐making process. Diagnostic endoscopic procedures with or without biopsy can often be done without interruption of antithrombotic therapy. If possible, elective procedures with high bleeding risk should be delayed in patients on antithrombotic therapy for conditions with high thrombotic risk. If high‐risk procedures cannot be delayed in these patients, thienopyridines, traditional and novel anticoagulants are usually withheld, whereas aspirin withdrawal is decided on a case by case basis. In patients with high thrombotic risk, communication with the prescribing clinician before proceeding to procedures with high bleeding risk is particularly important in optimizing the peri‐procedural management plan of antithrombotic therapy.     

The Medical and Endovascular Treatment of PAD: A Review of the Guidelines and Pivotal Clinical Trials

Peripheral arterial disease (PAD) is a global health problem. The risk factors for developing PAD have been clearly described in the literature, as have the medical therapies and preventative strategies for the prevention and treatment of PAD. Unfortunately, PAD patients remain undertreated with regard to guideline-directed medical therapy. During the last 2 decades, endovascular therapies for PAD have evolved such that randomized controlled trial level data are available for the treatment of lower extremity PAD at every major anatomic segment. Furthermore, endovascular therapy has evolved to the point that among experienced operators, an endovascular first strategy is reasonable for the treatment of most patients with intermittent claudication or critical limb ischemia.     

Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial.

OBJECTIVES: The purpose of this study was to determine the possible benefit of dual antiplatelet therapy in patients with prior myocardial infarction (MI), ischemic stroke, or symptomatic peripheral arterial disease (PAD). BACKGROUND: Dual antiplatelet therapy with clopidogrel plus aspirin has been validated in the settings of acute coronary syndromes and coronary stenting. The value of this combination was recently evaluated in the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial, where no statistically significant benefit was found in the overall broad population of stable patients studied. METHODS: We identified the subgroup in the CHARISMA trial who were enrolled with documented prior MI, ischemic stroke, or symptomatic PAD. RESULTS: A total of 9,478 patients met the inclusion criteria for this analysis. The median duration of follow-up was 27.6 months. The rate of cardiovascular death, MI, or stroke was significantly lower in the clopidogrel plus aspirin arm than in the placebo plus aspirin arm: 7.3% versus 8.8% (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.72 to 0.96, p = 0.01). Additionally, hospitalizations for ischemia were significantly decreased, 11.4% versus 13.2% (HR 0.86, 95% CI 0.76 to 0.96, p = 0.008). There was no significant difference in the rate of severe bleeding: 1.7% versus 1.5% (HR 1.12, 95% CI 0.81 to 1.53, p = 0.50); moderate bleeding was significantly increased: 2.0% versus 1.3% (HR 1.60, 95% CI 1.16 to 2.20, p = 0.004). CONCLUSIONS: In this analysis of the CHARISMA trial, the large number of patients with documented prior MI, ischemic stroke, or symptomatic PAD appeared to derive significant benefit from dual antiplatelet therapy with clopidogrel plus aspirin. Such patients may benefit from intensification of antithrombotic therapy beyond aspirin alone, a concept that future trials will need to validate. (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA]; http://clinicaltrials.gov/ct/show/NCT00050817?order=1; NCT00050817).     

Major Adverse Limb Events and Mortality in Patients With Peripheral Artery Disease: The COMPASS Trial

Background

Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There is limited information on the prognosis of patients who experience MALE.

A Multidisciplinary Approach on the Perioperative Antithrombotic Management of Patients With Coronary Stents Undergoing Surgery: Surgery After Stenting 2

Perioperative management of antithrombotic therapy in patients treated with coronary stents undergoing surgery remains poorly defined. Importantly, surgery represents a common reason for premature treatment discontinuation, which is associated with an increased risk in mortality and major adverse cardiac events. However, maintaining antithrombotic therapy to minimize the incidence of perioperative ischemic complications may increase the risk of bleeding complications. Although guidelines provide some recommendations with respect to the perioperative management of antithrombotic therapy, these have been largely developed according to the thrombotic risk of the patient and a definition of the hemorrhagic risk specific to each surgical procedure, key to defining the trade-off between ischemia and bleeding, is not provided. These observations underscore the need for a multidisciplinary collaboration among cardiologists, anesthesiologists, hematologists and surgeons to reach this goal. The present document is an update on practical recommendations for standardizing management of antithrombotic therapy management in patients treated with coronary stents (Surgery After Stenting 2) in various types of surgery according to the predicted individual risk of thrombotic complications against the anticipated risk of surgical bleeding complications. Cardiologists defined the thrombotic risk using a “combined ischemic risk” approach, while surgeons classified surgeries according to their inherent hemorrhagic risk. Finally, a multidisciplinary agreement on the most appropriate antithrombotic treatment regimen in the perioperative phase was reached for each surgical procedure.     

EKOS™ ultrasound – accelerated catheter – directed thrombolysis for acutely occluded femoro-popliteal graft

Acute limb ischemia due to bypass thrombotic occlusion may occur in patients with poor collateral circulation. It constitutes a medical emergency with increased morbidity, mortality and risk for limb amputation. Although the management of acute limb ischemia due to native artery occlusion is well studied, the optimal approach of acute bypass graft failure resulting in acute limb ischemia is uncertain. We present a case of acute limb ischemia in a patient with femoro-femoral and femoro-popliteal graft who presented with acute limb ischemia due to acute thrombotic occlusion of his femoro-popliteal graft. The patient was successfully managed with ultrasound-enhanced catheter-directed thrombolysis using the EkoSonic® endovascular system with excellent clinical and angiographic results. To our knowledge this is the first published report of the use of the EkoSonic® system for this indication.     

Therapy insight: peripheral arterial disease and diabetes--from pathogenesis to treatment guidelines

The increased risk of atherothrombotic events present in all patients with peripheral arterial disease (PAD) is amplified with concomitant diabetes. Moreover, diabetes is associated with increased PAD severity. This Review summarizes atherothrombosis and PAD in patients with diabetes, and American College of Cardiology and American Heart Association guidelines for management of patients with PAD. Patients with PAD and diabetes require optimal limb care and aggressive cardiovascular risk reduction. An LDL cholesterol level of less than 1.8 mmol/l (<70 mg/dl) is the therapeutic goal in these patients, and this target should be pursued using an aggressive statin regimen. Fibrate therapy can also be indicated. beta-blockers and angiotensin-converting-enzyme inhibitors reduce cardiovascular events in high-risk patient populations, and these agents are recommended for use in patients with both diabetes and PAD. Blood pressure of less than 130/80 mmHg should be achieved, and glycated hemoglobin should be reduced to below 7%. Patients should also receive indefinite antiplatelet therapy with aspirin or clopidogrel. For patients with claudication, a supervised exercise program and cilostazol therapy to improve PAD symptoms and walking distance form the main noninvasive components of therapy. Revascularization can also be indicated in carefully selected patients with claudication. For patients with critical limb ischemia, diagnostic testing by a vascular specialist will determine whether revascularization or amputation is feasible.     

Combining Antiplatelet and Antithrombotic Therapy (Triple Therapy): What Are the Risks and Benefits?

Most patients with mechanical heart valves and many patients with atrial fibrillation will require long-term anticoagulation therapy. For patients with mechanical prosthetic valves, only warfarin is indicated. However, for patients with nonvalvular atrial fibrillation who are at increased risk for embolic stroke, one of the newer antithrombotic medications, such as rivaroxaban, dabigatran, and apixaban, also can be used. Patients with indications for antithrombotic therapy often will have coexisting vascular disease, such as coronary artery disease, requiring concomitant antiplatelet therapy with aspirin alone or more commonly with a dual antiplatelet regimen, aspirin and clopidogrel, or prasugrel or ticagrelor. The risks and benefits of this approach are still not well defined, and current guidelines have included recommendations based primarily on expert opinion.     

Prophylactic antithrombotic therapy for patients with systemic lupus erythematosus with or without antiphospholipid antibodies: do the benefits outweigh the risks? A decision analysis

BACKGROUND: A high incidence of both arterial and venous thromboembolic events has been reported in patients with systemic lupus erythematosus (SLE), but the risks and benefits of primary prophylactic antithrombotic therapy have not been assessed. We measured the clinical benefit of 3 antithrombotic regimens in patients with SLE without antiphospholipid antibodies, with anticardiolipin antibodies, or with lupus anticoagulant. METHODS: A Markov decision analysis was used to evaluate prophylactic aspirin therapy, prophylactic oral anticoagulant therapy, and observation. Input data were obtained by literature review. Clinical practice was simulated in a hypothetical cohort of patients with SLE who had not experienced any previous episode of arterial or venous thromboembolic events. For each strategy, we measured numbers of thromboembolic events prevented and major bleeding episodes induced, and quality-adjusted survival years. RESULTS: Prophylactic aspirin therapy was the preferred strategy in all settings, the number of prevented thrombotic events exceeding that of induced bleeding episodes. In the baseline analysis (40-year-old patients with SLE), the gain in quality-adjusted survival years achieved by prophylactic aspirin compared with observation ranged from 3 months in patients without antiphospholipid antibodies to 11 months in patients with anticardiolipin antibodies or lupus anticoagulant. Prophylactic oral anticoagulant therapy provided better results than prophylactic aspirin only in patients with lupus anticoagulant and an estimated bleeding risk of 1% per year or less. CONCLUSIONS: Prophylactic aspirin should be given to all patients with SLE to prevent both arterial and venous thrombotic manifestations, especially in patients with antiphospholipid antibodies. In selected patients with lupus anticoagulant and a low bleeding risk, prophylactic oral anticoagulant therapy may provide a higher utility.     

Rivaroxaban Plus Aspirin in Patients With Vascular Disease and Renal Dysfunction: From the COMPASS Trial

BackgroundChronic kidney disease is associated with an increased risk of both bleeding and ischemic cardiovascular events.ObjectiveThe purpose of this study was to determine the balance of risks and benefits from the dual pathway antithrombotic regimen (rivaroxaban 2.5 mg twice daily [bd] plus aspirin, compared with aspirin) in vascular patients with or without moderate renal dysfunction.MethodsThis was a secondary analysis of the COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS) trial involving 27,395 patients with chronic coronary or peripheral artery disease.ResultsIn COMPASS, 21,111 patients had an estimated glomerular filtration rate (GFR) at baseline of ≥60 ml/min, 6,276 had a GRF of <60 ml/min. Both the primary efficacy outcome (cardiovascular death, myocardial infarction, or stroke) and major bleeding were more frequent in those with renal dysfunction, and the frequency of these outcome events was inversely related to GFR. However, the primary outcome was consistently reduced with rivaroxaban 2.5 mg bd plus aspirin, irrespective of GFR category (GFR ≥60 ml/min, 3.5% rivaroxaban plus aspirin, 4.5% aspirin alone, hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.64 to 0.90; GFR <60 ml/min, 6.4% rivaroxaban plus aspirin, 8.4% aspirin alone, HR: 0.75; 95% CI: 0.60 to 0.94). Major bleeding was more frequent with rivaroxaban 2.5 mg plus aspirin versus aspirin alone in those with GFR ≥60 ml/min (2.9% rivaroxaban plus aspirin, 1.6% aspirin alone, HR: 1.81; 95% CI: 1.44 to 2.28) and similarly in those with GFR <60 ml/min (3.9% rivaroxaban plus aspirin, 2.7% aspirin alone, HR: 1.47, 95% CI: 1.05 to 2.07).ConclusionsThe benefits of the dual pathway COMPASS regimen (rivaroxaban 2.5 mg bd plus aspirin), versus aspirin alone, are preserved in patients with moderate renal dysfunction without evidence of an excess hazard of bleeding.     

Effectiveness of revascularisation of the ulcerated foot in patients with diabetes and peripheral artery disease: A systematic review

In patients with diabetes, foot ulceration and peripheral artery disease (PAD), it is often difficult to determine whether, when and how to revascularise the affected lower extremity. The presence of PAD is a major risk factor for non‐healing and yet clinical outcomes of revascularisation are not necessarily related to technical success. The International Working Group of the Diabetic Foot updated systematic review on the effectiveness of revascularisation of the ulcerated foot in patients with diabetes and PAD is comprised of 64 studies describing >13 000 patients. Amongst 60 case series and 4 non‐randomised controlled studies, we summarised clinically relevant outcomes and found them to be broadly similar between patients treated with open vs endovascular therapy. Following endovascular revascularisation, the 1 year and 2 year limb salvage rates were 80% (IQR 78‐82%) and 78% (IQR 75‐83%), whereas open therapy was associated with rates of 85% (IQR 80‐90%) at 1 year and 87% (IQR 85‐88%) at 2 years, however these results were based on a varying combination of studies and cannot therefore be interpreted as cumulative. Overall, wound healing was achieved in a median of 60% of patients (IQR 50‐69%) at 1 year in those treated by endovascular or surgical therapy, and the major amputation rate of endovascular vs open therapy was 2% vs 5% at 30 days, 10% vs 9% at 1 year and 13% vs 9% at 2 years. For both strategies, overall mortality was found to be high, with 2% (1‐6%) perioperative (or 30 day) mortality, rising sharply to 13% (9‐23%) at 1 year, 29% (19‐48%) at 2 years and 47% (39‐71%) at 5 years. Both the angiosome concept (revascularisation directly to the area of tissue loss via its main feeding artery) or indirect revascularisation through collaterals, appear to be equally effective strategies for restoring perfusion. Overall, the available data do not allow us to recommend one method of revascularisation over the other and more studies are required to determine the best revascularisation approach in diabetic foot ulceration.