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The anticoagulant edoxaban, an oral inhibitor of activated factor X, does not require monitoring. As initial treatment for acute venous thromboembolism, heparin–edoxaban was noninferior to heparin–warfarin and caused less bleeding. Venous thromboembolism is the third most common cardiovascular disease after myocardial infarction and stroke, affecting at least 700,000 persons annually in North America. 1 – 3 The standard treatment consists of low-molecular-weight heparin followed by vitamin K antagonists. 4 A number of studies have established that new oral anticoagulants with or without initial heparin therapy are effective alternatives. 5 – 8 Edoxaban is a direct inhibitor of activated factor X with a rapid onset of action. It is administered orally once daily and has proven antithrombotic efficacy. 9 – 11 The Hokusai-VTE study was a randomized, double-blind clinical trial that was conducted to evaluate edoxaban for the . . .

Peripherally inserted central catheters (PICCs) are associated with an increased risk of venous thromboembolism. However, the size of this risk relative to that associated with other central venous catheters (CVCs) is unknown. We did a systematic review and meta-analysis to compare the risk of venous thromboembolism associated with PICCs versus that associated with other CVCs. We searched several databases, including Medline, Embase, Biosis, Cochrane Central Register of Controlled Trials, Conference Papers Index, and Scopus. Additional studies were identified through hand searches of bibliographies and internet searches, and we contacted study authors to obtain unpublished data. All human studies published in full text, abstract, or poster form were eligible for inclusion. All studies were of adult patients aged at least 18 years who underwent insertion of a PICC. Studies were assessed with the Newcastle–Ottawa risk of bias scale. In studies without a comparison group, the pooled frequency of venous thromboembolism was calculated for patients receiving PICCs. In studies comparing PICCs with other CVCs, summary odds ratios (ORs) were calculated with a random effects meta-analysis. Of the 533 citations identified, 64 studies (12 with a comparison group and 52 without) including 29 503 patients met the eligibility criteria. In the non-comparison studies, the weighted frequency of PICC-related deep vein thrombosis was highest in patients who were critically ill (13·91%, 95% CI 7·68–20·14) and those with cancer (6·67%, 4·69–8·64). Our meta-analysis of 11 studies comparing the risk of deep vein thrombosis related to PICCs with that related to CVCs showed that PICCs were associated with an increased risk of deep vein thrombosis (OR 2·55, 1·54–4·23, p<0·0001) but not pulmonary embolism (no events). With the baseline PICC-related deep vein thrombosis rate of 2·7% and pooled OR of 2·55, the number needed to harm relative to CVCs was 26 (95% CI 13–71). PICCs are associated with a higher risk of deep vein thrombosis than are CVCs, especially in patients who are critically ill or those with a malignancy. The decision to insert PICCs should be guided by weighing of the risk of thrombosis against the benefit provided by these devices. None.

Conventional anticoagulant treatment for acute deep vein thrombosis (DVT) effectively prevents thrombus extension and recurrence, but does not dissolve the clot, and many patients develop post-thrombotic syndrome (PTS). We aimed to examine whether additional treatment with catheter-directed thrombolysis (CDT) using alteplase reduced development of PTS. Participants in this open-label, randomised controlled trial were recruited from 20 hospitals in the Norwegian southeastern health region. Patients aged 18–75 years with a first-time iliofemoral DVT were included within 21 days from symptom onset. Patients were randomly assigned (1:1) by picking lowest number of sealed envelopes to conventional treatment alone or additional CDT. Randomisation was stratified for involvement of the pelvic veins with blocks of six. We assessed two co-primary outcomes: frequency of PTS as assessed by Villalta score at 24 months, and iliofemoral patency after 6 months. Analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00251771. 209 patients were randomly assigned to treatment groups (108 control, 101 CDT). At completion of 24 months' follow-up, data for clinical status were available for 189 patients (90%; 99 control, 90 CDT). At 24 months, 37 (41·1%, 95% CI 31·5–51·4) patients allocated additional CDT presented with PTS compared with 55 (55·6%, 95% CI 45·7–65·0) in the control group (p=0·047). The difference in PTS corresponds to an absolute risk reduction of 14·4% (95% CI 0·2–27·9), and the number needed to treat was 7 (95% CI 4–502). Iliofemoral patency after 6 months was reported in 58 patients (65·9%, 95% CI 55·5–75·0) on CDT versus 45 (47·4%, 37·6–57·3) on control (p=0·012). 20 bleeding complications related to CDT included three major and five clinically relevant bleeds. Additional CDT should be considered in patients with a high proximal DVT and low risk of bleeding. South-Eastern Norway Regional Health Authority; Research Council of Norway; University of Oslo; Oslo University Hospital.

Pulmonary embolism is the third most common cause of death from cardiovascular disease after heart attack and stroke. Sequelae occurring after venous thromboembolism include chronic thromboembolic pulmonary hypertension and post-thrombotic syndrome. Venous thromboembolism and atherothrombosis share common risk factors and the common pathophysiological characteristics of inflammation, hypercoagulability, and endothelial injury. Clinical probability assessment helps to identify patients with low clinical probability for whom the diagnosis of venous thromboembolism can be excluded solely with a negative result from a plasma D-dimer test. The diagnosis is usually confirmed with compression ultrasound showing deep vein thrombosis or with chest CT showing pulmonary embolism. Most patients with venous thromboembolism will respond to anticoagulation, which is the foundation of treatment. Patients with pulmonary embolism should undergo risk stratification to establish whether they will benefit from the addition of advanced treatment, such as thrombolysis or embolectomy. Several novel oral anticoagulant drugs are in development. These drugs, which could replace vitamin K antagonists and heparins in many patients, are prescribed in fixed doses and do not need any coagulation monitoring in the laboratory. Although rigorous clinical trials have reported the effectiveness and safety of pharmacological prevention with low, fixed doses of anticoagulant drugs, prophylaxis remains underused in patients admitted to hospital at moderate risk and high risk for venous thromboembolism. In this Seminar, we discuss pulmonary embolism and deep vein thrombosis of the legs.

In this trial, 261 patients with chronic thromboembolic pulmonary hypertension were assigned to placebo or to the soluble guanylate cyclase stimulator riociguat. At 16 weeks, riociguat had significantly improved the 6-minute walk distance and pulmonary vascular resistance. Chronic thromboembolic pulmonary hypertension is characterized by obstruction of the pulmonary vasculature by residual organized thrombi, 1 leading to increased pulmonary vascular resistance, progressive pulmonary hypertension, and right ventricular failure. 2 , 3 Patients with chronic thromboembolic pulmonary hypertension have a poor prognosis unless they receive treatment early. 4 Pulmonary endarterectomy is the standard treatment for chronic thromboembolic pulmonary hypertension and is the only potentially curative treatment. 5 However, surgery is not an option for all patients; some patients are ineligible for surgery owing to the occlusion of distal vessels or coexisting conditions, some decline surgery, and some do not have access to expert surgical . . .

Patients with venous thromboembolism who had received initial anticoagulant therapy were studied in two trials of dabigatran. Dabigatran was effective in preventing recurrent venous thromboembolism and carried a lower risk of bleeding than warfarin but a higher risk than placebo. Anticoagulant treatment with vitamin K antagonists is recommended for patients with venous thromboembolism. 1 Most patients receive at least 3 months of treatment. Long-term treatment is recommended if there are risk factors for recurrence, such as multiple thrombotic episodes. 1 In the absence of clear contraindications to anticoagulant therapy, the risk of major bleeding is approximately 1% per year with extended vitamin K antagonist therapy after venous thromboembolism. 2 The risk of major bleeding, together with the need for frequent laboratory monitoring and dose adjustments, makes long-term treatment problematic. Dabigatran, a direct thrombin inhibitor, does not require frequent monitoring and dose adjustments. At . . .

This article reviews the evaluation of patients with acute limb ischemia, including assessment of temperature, appearance, and pulses, by palpation and Doppler. Strategies for treatment of viable limbs are reviewed. Foreword This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations. Stage A 57-year-old man presents with an acute onset of left foot pain, numbness, and partial loss of motor function. Four months ago, he underwent endovascular treatment for disabling claudication, which included placement of overlapping polytetrafluoroethylene-coated stents in the left superficial femoral and popliteal arteries. His popliteal and pedal pulses are absent, and the foot is cool and mottled. Angiography reveals complete occlusion of the stent, with thrombosis extending distally into the popliteal and tibial arteries below the knee. How should his case be managed? The Clinical Problem Acute limb ischemia is defined as a sudden decrease in limb perfusion . . .

In patients with a recent transient ischemic attack or stroke attributed to 70 to 99% stenosis of a major intracranial artery, aggressive medical management was superior to aggressive medical management plus percutaneous transluminal angioplasty and stenting. Atherosclerotic intracranial arterial stenosis is one of the most common causes of stroke worldwide 1 – 6 and is associated with a high risk of recurrent stroke. 7 – 9 Patients with a recent transient ischemic attack (TIA) or stroke and severe stenosis (70 to 99% of the diameter of a major intracranial artery) are at particularly high risk for recurrent stroke in the territory of the stenotic artery (approximately 23% at 1 year) despite treatment with aspirin and standard management of vascular risk factors. 8 , 10 Therefore, alternative therapies are urgently needed for these patients. Two strategies have emerged for the treatment of high-risk . . .

Chronic thromboembolic pulmonary hypertension can develop after acute pulmonary embolus but is often overlooked until pulmonary hypertension has led to dyspnea and right ventricular dysfunction. This review provides a guide to early diagnosis and management. Chronic thromboembolic pulmonary hypertension is defined as mean pulmonary-artery pressure greater than 25 mm Hg that persists 6 months after pulmonary embolism is diagnosed. The 2008 World Symposium on Pulmonary Hypertension 1 emphasized the importance of chronic thromboembolic pulmonary hypertension, which occurs in 2 to 4% of patients after acute pulmonary embolism. 2 , 3 The frequency of this condition among patients with pulmonary hypertension is unknown. Patients with chronic thromboembolic pulmonary hypertension generally present in their 40s, although this condition has been reported in patients in other age groups. 2 The diagnosis is often overlooked because many patients do not have a history . . .

Gastroesophageal varices are present at diagnosis in almost half of patients with cirrhosis, and variceal hemorrhage continues to be a lethal complication of cirrhosis. This review explains the three main challenges in clinical management: primary prophylaxis to prevent a first episode of hemorrhage, the treatment of acute bleeding episodes, and secondary prophylaxis to prevent recurrence of variceal hemorrhage. This review explains the three main challenges in clinical management: primary prophylaxis to prevent a first episode of hemorrhage, the treatment of acute bleeding episodes, and secondary prophylaxis to prevent recurrence of variceal hemorrhage. Variceal hemorrhage is a lethal complication of cirrhosis, particularly in patients in whom clinical decompensation (i.e., ascites, encephalopathy, a previous episode of hemorrhage, or jaundice) has already developed. Practice guidelines for the management of varices and variceal hemorrhage 1 in cirrhosis are mostly based on evidence in the literature that has been summarized and prioritized at consensus conferences. 2 , 3 There are three main areas of management: primary prophylaxis to prevent a first episode of variceal hemorrhage, treatment of the acute bleeding episode, and secondary prophylaxis (prevention of recurrent variceal hemorrhage). Natural History and Epidemiology Gastroesophageal varices are present in almost half . . .