Outpatient treatment of symptomatic pulmonary embolism: A systematic review and meta-analysis

Background

Patients with acute deep vein thrombus (DVT) can safely be treated as outpatients. However the role of outpatient treatment in patients diagnosed with a pulmonary embolism (PE) is controversial. We sought to determine the safety of outpatient management of patients with acute symptomatic PE.

Materials and Methods

A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews. Pooled proportions for the different outcomes were calculated.

Results

A total of 1258 patients were included in the systematic review. The rate of recurrent venous thromboembolism (VTE) in patients with PE managed as outpatients was 1.47% (95% CI: 0.47 to 3.0%; I²: 65.4%) during the 3 month follow-up period. The rate of fatal PE was 0.47% (95% CI: 0.16 to 1.0%; I²: 0%). The rates of major bleeding and fatal intracranial hemorrhage were 0.81% (95% CI: 0.37 to 1.42%; I²: 0%) and 0.29% (95% CI: 0.06 to 0.68%; I²: 0%), respectively. The overall 3 month mortality rate was 1.58% (95% CI: 0.71 to 2.80%; I²: 45%). The event rates were similar if employing risk stratification models versus using clinical gestalt to select appropriate patients for outpatient management.

Conclusions

Independent of the risk stratification methods used, the rate of adverse events associated with outpatient PE treatment seems low. Based on our systematic review and pooled meta-analysis, low-risk patients with acute PE can safely be treated as outpatients if home circumstances are adequate.     

Recombinant tissue plasminogen activator for hemodynamically stable patients experiencing an acute pulmonary embolism: A meta-analysis

Background

The role of thrombolytic therapy for the initial treatment of hemodynamically stable patients experiencing an acute pulmonary embolism remains controversial.

Methods and Results

We performed a meta-analysis of randomized trials comparing between administration of recombinant tissue plasminogen activator (rt-PA) and heparin in hemodynamically stable patients experiencing an acute pulmonary embolism. Seven trials, involving 594 patients, were included in this meta-analysis. Compared with heparin, rt-PA was associated with a non-significant reduction in death (2.75% versus 3.96%; RR 0.69, 95% CI 0.31-1.52, P for heterogeneity = 0.520) and recurrent pulmonary embolism (2.13% versus 3.34%; RR 0.70, 95% CI 0.28-1.73), and a non-significant increase in major bleeding (5.15% versus 4.29%; RR 1.06, 95% CI 0.520-2.150). Similar results were found based on a subgroup analysis of patients displaying echocardiographic evidence of right ventricular dysfunction (RVD). In contrast, rt-PA treatment was associated with a significant reduction in escalation of care in trials that also enrolled patients displaying RVD compared with heparin treatment (6.56% versus 19.7%; RR 0.34, 95% CI 0.20-0.65).

Conclusion

The currently available data provide no evidence for a benefit of administration of rt-PA compared with heparin for the initial treatment of hemodynamically stable patients experiencing an acute pulmonary embolism. However, rt-PA is partially beneficial specifically among patients displaying RVD.     

Managing pulmonary embolism from presentation to extended treatment

Pulmonary embolism (PE) remains a major healthcare problem. PE presents with a variety of non-specific symptoms, and confirmation of diagnosis involves the use of clinical risk scores, scanning techniques and laboratory tests. Treatment choice is informed by the risk of sudden death, with high-risk patients recommended to receive thrombolytic therapy or thrombectomy. Patients with less severe presentations are given anticoagulant therapy, traditionally with parenteral heparins in the acute phase of treatment, transitioning to oral vitamin K antagonists (VKAs). The limitations of these agents and the introduction of non-VKA oral anticoagulants challenge this paradigm. To date, clinical studies of four non-VKA oral anticoagulants to treat acute thrombosis have been published, and rivaroxaban is now approved for treatment and prevention of PE (and deep vein thrombosis). Rivaroxaban and apixaban alone, and dabigatran and edoxaban after parenteral anticoagulant induction, were non-inferior to enoxaparin/VKA for the prevention of recurrent venous thromboembolism; the risk of major bleeding was similar with dabigatran and edoxaban and significantly reduced with rivaroxaban and apixaban. Patients with an initial PE are recommended to receive continued anticoagulation for 3 months or longer, depending on individual risk factors, and studies of non-VKA oral anticoagulants have shown a continued benefit for up to 2 years, without a significantly increased risk of major bleeding. Given that the non-VKA oral anticoagulants are given at fixed doses without the need for routine coagulation monitoring, their adoption is likely to ease the burden on both PE patients and healthcare practitioners when longer-term or extended anticoagulation is warranted.     

A systematic review of rivaroxaban versus enoxaparin in the prevention of venous thromboembolism after hip or knee replacement

Introductions

Rivaroxaban is a novel Xa inhibitor with an encouraging anti-thrombosis effect. The aim of this study is to assess whether rivaroxaban is superior to enoxaparin in venous thromboembolism prevention after knee- or hip-joint replacement.

Materials and Methods

We searched for reports of randomized controlled trials on rivaroxaban versus enoxaparin in venous thromboembolism prophylaxis after knee- or hip-joint replacement in the Cochrane library, Embase, Pubmed, the Ovid database, and Chinese databases including VIP, CNKI, and CBM. Correlated data was extracted and analyzed.

Results

Eight studies involving 15246 patients were included, and all were randomized controlled studies. The methodological quality of six of the trials was generally moderate, while that of the remaining two was considered high quality. 10 mg rivaroxaban daily is more effective than 40 mg/30 mg enoxaparin daily after the joint replacement in respect of the incidence of venous thromboembolism (P < 0.0001, RR = 0.38; P = 0.05, RR = 0.77, respectively). No significant difference between 10 mg rivaroxaban daily and 40 mg/30 mg enoxaparin daily were found in major postoperative bleeding (P = 0.45, RR = 1.31;P = 0.34, RR = 1.61, respectively). With respect to other outcomes, rivaroxaban is not inferior to enoxaparin, while extended therapy with rivaroxaban (> 30 d) is more effective than short-term therapy (< 15 d) in relation to the incidence of venous thromboembolism (1.36% versus 10.13%).

Conclusions

Rivaroxaban is superior to enoxaparin in venous thromboembolism prophylaxis after hip- or knee-joint replacement. Extended therapy – longer than 30 d – is recommended.     

Recognition, treatment, and prevention of heparin-induced thrombocytopenia: review and update

Heparin-induced thrombocytopenia (HIT) is one of the most important life- and limb-threatening adverse drug events encountered by physicians. Serious sequelae associated with HIT can be avoided with early recognition and appropriate treatment. This review examines the recommendations published in 2004 by the American College of Chest Physicians on the recognition, treatment, and prevention of HIT together with more recent data, especially regarding treatment with direct thrombin inhibitors.     

The role of inherited thrombophilia in patients with isolated pulmonary embolism: A systematic review and a meta-analysis of the literature

Introduction

Venous thromboembolism (VTE) is a common vascular disease that results in deep venous thrombosis (DVT) and pulmonary embolism (PE). Factor V Leiden mutation (FVL) and G20210A prothrombin mutation (PTM) are associated with an increased risk of VTE. Recent studies have reported a lower prevalence of FVL in patients with isolated PE than in patients with DVT with or without PE, suggesting the possibility that the prevalence of FVL in patients with isolated PE may be not significantly different from that of the general population. To address this issue, we performed a systematic review and a meta-analysis of published studies that assessed the prevalence of FVL and/or PTM in patients with isolated PE and in controls without VTE.

Methods

MEDLINE and EMBASE databases were searched up to October 2013. Pooled odds Ratios (OR) and 95% confidence intervals (CIs) were calculated using a random-effects model. Statistical heterogeneity was evaluated using the Cochran Q and I² statistics.

Results

Eighteen studies totalling more than 11,000 patients were included. FVL was found significantly more often in patients presenting isolated PE than in controls (OR 2.06; 95% CI 1.66, 2.56; p < 0.0001). The prevalence of PTM was also significantly different in patients presenting with isolated PE than in controls (OR 2.64, 95% CI 1.92, 3.63; p < 0.0001). Heterogeneity among studies was low.

Conclusion

FVL and PTM are both associated with isolated PE. However, the association magnitude between PE and FVL mutation appeared to be lower compared to that observed in the general population of VTE patients.     

Pregnancy-related venous thromboembolism: risk and the effect of thromboprophylaxis

Venous thromboembolism (VTE) is a leading cause of maternal mortality and morbidity during pregnancy in developed countries. The incidence of VTE per pregnancy-year increases about 4-fold during pregnancy and at least 14-fold during the puerperium. Risk factors include a personal history of VTE, presence of inherited or acquired thrombophilia, a family history of VTE and general medical conditions, such as immobilisation, overweight, varicose veins, some haematological diseases and inflammatory disorders. VTE is considered potentially preventable with the prophylactic administration of anticoagulants, but there are no high quality randomized clinical trials that compared different strategies of thromboprophylaxis in pregnant women. Balancing the absolute risk of VTE against the risks of exposure to anticoagulants, this review provides advice regarding which women may benefit from thromboprophylaxis during and after pregnancy.     

Venous thromboembolism risk assessment and thromboprophylaxis among hospitalized acute medical patients in China - the RAMP study

Background

In developed countries, hospitalized patients with acute medical conditions are at significant risk for venous thromboembolism (VTE). Little is known about VTE risk and prophylaxis practices in China.

Objective

To determine the VTE risk and the frequency of recommended VTE prophylaxis in hospitalized Chinese patients with acute medical conditions.

Methods

Multi-center, cross-sectional, observational study. Eligibility criteria: ≥ 30 years, admitted to an intensive care unit (ICU)/coronary care unit (CCU) for acute medical illness, had ≥ 1 VTE risk factor/1 disease that predisposes to VTE, and provided informed consent. We used 2004 American College of Chest Physicians (ACCP) evidence-based consensus guidelines to assess VTE risk and the frequency of recommended VTE prophylaxis.

Results

1247 patients from 19 hospitals in 11 cities across 11 provinces of China were enrolled from July 2007 to June 2008. 57.3% patients had > 2 VTE risk factors. Only 20.2% received ACCP-recommended VTE prophylaxis (CCU patients: 22.7%, ICU patients: 16.9%, p = 0.0117).

Limitations

Excluding some patients with VTE risk factors did not allow assessment of the prevalence of VTE risk in the acute hospital-care setting. We could not determine whether the duration of prophylaxis complied with the ACCP recommendations. Our results may not be representative of hospitals in small cities/rural areas in China.

Conclusions

The prevalence of VTE risk factors in Chinese patients was similar to that in developed countries; however, only a small proportion of eligible patients received the recommended VTE prophylaxis. Our findings highlight the need for dissemination and implementation of appropriate VTE prophylaxis guidelines in China.     

Performance of the Wells score in patients with suspected pulmonary embolism during hospitalization: A delayed-type cross sectional study in a community hospital

Introduction

The role of the Wells score for patients who develop signs and symptoms of pulmonary embolism (PE) during hospitalization has not been sufficiently validated. The aim of this study is to evaluate the performance of the Wells score for inpatients with suspected PE and to evaluate the prevalence of pulmonary embolism.

Materials and Methods

We conducted a cross sectional study nested in the prospective Institutional Registry of Thromboembolic Disease at Hospital Italiano de Buenos Aires from June 2006 to March 2011. We included patients who developed symptoms of pulmonary embolism during hospitalization. Patients were stratified based on the Wells score as PE likely (> 4 points) or PE unlikely (≤ 4 points). The presence of pulmonary embolism was defined by pre-specified criteria.

Results

Six hundred and thirteen patients met the inclusion criteria, with an overall prevalence of PE of 36%. Two hundred and nineteen (34%) were classified as PE likely and 394 (66%) as PE unlikely with a prevalence of PE of 66% and 20%, respectively. The Wells score showed a sensitivity of 65 (95% CI 59-72), specificity 81 (95% CI 77-85), positive predictive value 66 (95% CI 60-72) and negative predictive value 80 (95% CI 77-84).

Conclusions

The Wells Score is accurate to predict the probability of PE in hospitalized patients and this population had a higher prevalence of PE than other cohorts. However, the score is not sufficiently predictive to rule out a potentially fatal disorder.     

Outcomes of management of acute coronary syndrome in patients with congenital bleeding disorders: A single center experience and review of the literature

Introduction

Evidence-based guidelines for the management of acute coronary syndrome (ACS) in patients with congenital bleeding disorders are lacking and largely confined to case reports.

Methods

Outcomes of acute and long-term management of ACS in patients with mild hemophilia and von Willebrand disease managed at our institution from 2000-2011 were reviewed.

Results

Between 2000-2011, 8 patients (median age 74 years) experienced 10 ACS events. In the emergency room, 3 of 4 patients received aspirin 325 mg and intravenous unfractionated heparin therapy, with no acute bleeding complications. The 8 patients underwent 10 coronary angiography procedures. Prophylactic factor concentrates were not administered for 6/10 (60%) of the procedures; bleeding complications (groin hematoma) occurred in 1/6 (17%). Two patients receiving bare metal stents and glycoprotein IIb/IIIa inhibitor infusion with factor concentrates experienced no acute hemorrhagic complications. On discharge, aspirin was initiated/continued in 6/10 events; the 2 patients receiving dual anti-platelet therapy for 1 month did not receive factor concentrates and experienced no bleeding complications. During a median follow-up of 8.5 years (1 - 11.5 years), 2 of 5 patients developed minor bleeding complications while on aspirin.

Conclusion

Our data demonstrate that in patients with mild congenital bleeding disorders, despite not receiving factor concentrates prior to coronary angiography, the acute management of ACS did not result in severe hemorrhagic complications. Short-term dual anti-platelet therapy seemed to be well tolerated. In patients receiving long-term aspirin for secondary prevention for ACS, bleeding complications were mild, however such patients warrant close follow-up.