Effect of an interactive, educational app about venous thromboembolism and anticoagulation on patient satisfaction: A randomized controlled trial.

BACKGROUND: Adequate patient education is essential for patients to engage in shared decision-making when deciding to stop or continue anticoagulation after 3 months for venous thromboembolism (VTE). Our objectives were to evaluate the effect of an interactive, educational app on patients' level of satisfaction with information, perceived level of knowledge, decisional conflict and extent of shared decision-making when deciding on treatment duration of VTE. MATERIALS AND METHODS: This randomized controlled trial in 1 academic and 3 general Dutch hospitals included adult patients diagnosed with VTE without malignancy or prolonged anticoagulation for other indications. Patients were randomized in 1:1 ratio to receive the app (intervention group) in addition to hospital-specific standard of care. The app, created for this study, contains information on VTE and anticoagulation on an interactive timeline. In the week preceding the consultation when treatment duration is decided, patients were provided with daily videos using push notifications. Outcomes were assessed through self-reported questionnaires at baseline, 1-2 days before and 1 day after consultation. Data were analyzed using t-tests and linear mixed models for repeated measurements. RESULTS: Data of 56 patients were analyzed (mean age 57 ± 13; 27% female). On a numeric rating scale from 0 to 10, patients who received the app were 0.9 points (95%CI 0.0-1.7; p 0.04) more satisfied with the provided information. Patients who received the app experienced significantly less decisional conflict. No differences in other outcomes were observed. CONCLUSIONS: An educational app about VTE and anticoagulation increases patients' satisfaction and reduces decisional conflict when deciding on treatment duration of VTE. This study was registered in the Netherlands Trial Register (NL7037).

Elastic compression stockings one year after DVT diagnosis: Who might discontinue?

BACKGROUND: Elastic compression stockings (ECS) are uncomfortable to wear but may prevent post-thrombotic syndrome (PTS). The ability to predict PTS may help clinical decision making regarding the optimal duration of ECS after deep vein thrombosis (DVT). AIMS: Predefined endpoint analysis of the Octavia study that randomized patients who compliantly used ECS up to one year after DVT to continue or discontinue ECS treatment. Primary aim was to identify predictors of PTS. METHODS: Patient characteristics were collected and ultrasonography was performed to assess reflux, residual thrombosis and persistent thrombus load 12 months after DVT. Multivariable analyses were performed to identify factors related to PTS. RESULTS: Thrombus score ≥ 3, BMI ≥ 26, duration of symptoms before DVT diagnosis ≥ 8 days and a Villalta score of 2-4 points were statistically significant predictors of PTS. The predictive value for PTS for the assessed variables was not different between the 2 treatment groups. In the stop ECS group, 3.2% (95%CI 0.08-18) of patients without any predictors for PTS were diagnosed with mild PTS during follow-up, and none with severe PTS, for a sensitivity of 98% (95% CI 89-100), a specificity of 14% (95% CI 10-20), a positive predictive value of 20% (95% CI 19-22), and a negative predictive value of 97% (95% CI 81-100). CONCLUSION: We identified 4 predictors of PTS occurring in the 2nd year after DVT. Our findings may be used to decide on whether to continue ECS treatment for an additional year, after one year of compliant ECS use, keeping in mind that patients with none of the predictors will have the lowest PTS incidence.

No added value of the age-adjusted D-dimer cut-off to the YEARS algorithm in patients with suspected pulmonary embolism.

Essentials Imaging is warranted in the majority of patients to confirm or rule out pulmonary embolism (PE). The age-adjusted D-dimer (ADJUST) reduced the number of required imaging tests in patients ≥ 50 years. The YEARS algorithm was designed to improve the efficiency in patients with suspected PE. There was no added value of implementing ADJUST in the YEARS algorithm in our cohort. SUMMARY: Background The YEARS algorithm was designed to simplify the diagnostic work-up of pulmonary embolism (PE) and to reduce the number of necessary computed tomography pulmonary angiography (CTPA) scans. An alternative strategy to reduce the number of CTPAs is the age-adjusted D-dimer cut-off (ADJUST) in patients aged 50 years or older. We aimed to investigate whether a combination of both diagnostic strategies might save additional CTPAs. Methods The YEARS algorithm consists of three items (clinical signs of deep venous thrombosis, hemoptysis, 'PE most likely diagnosis') with simultaneous D-dimer testing using a pre-test dependent threshold. We performed a post hoc analysis in 3465 patients managed according to YEARS to compare the number of patients managed without CTPA scans and associated diagnostic failures in hypothetical scenarios with different YEARS-ADJUST combinations. Results Following the YEARS algorithm, 1651 patients (48%) were managed without CTPA; PE was diagnosed in 456 (13%) patients at baseline and 18 patients with initial normal testing suffered venous thromboembolism (VTE) during 3-month follow-up (failure rate 0.61%; 95% confidence interval [CI], 0.36-0.96). If ADJUST had been fully integrated in YEARS, 1627 patients (47%) would have been managed without CTPA (absolute decrease of 0.69%; 95% CI -1.7 to 3.0), at cost of four additional missed PE diagnoses at baseline, for a projected 3-month VTE failure rate of 0.75% (95% CI, 0.49-1.13). None of the other studied scenarios showed relevant improvements in efficiency as well, but all led to more missed diagnoses. Conclusion In our cohort, there was no added value of implementing ADJUST in the YEARS algorithm.

Assessing clinical probability of pulmonary embolism: prospective validation of the simplified Geneva score.

Essentials The simplified Geneva score allows easier pretest probability assessment of pulmonary embolism (PE). We prospectively validated this score in the ADJUST-PE management outcome study. The study shows that it is safe to manage patients with suspected PE according to this score. The simplified Geneva score is now ready for use in routine clinical practice. SUMMARY: Background Pretest probability assessment by a clinical prediction rule (CPR) is an important step in the management of patients with suspected pulmonary embolism (PE). A limitation to the use of CPRs is that their constitutive variables and corresponding number of points are difficult to memorize. A simplified version of the Geneva score (i.e. attributing one point to each variable) has been proposed but never been prospectively validated. Aims Prospective validation of the simplified Geneva score (SGS) and comparison with the previous version of the Geneva score (GS). Methods In the ADJUST-PE study, which had the primary aim of validating the age-adjusted D-dimer cut-off, the SGS was prospectively used to determine the pretest probability in a subsample of 1621 study patients. Results Overall, PE was confirmed in 294 (18.1%) patients. Using the SGS, 608 (37.5%), 980 (60.5%) and 33 (2%) were classified as having a low, intermediate and high clinical probability. Corresponding prevalences of PE were 9.7%, 22.4% and 45.5%; 490 (30.1%) patients with low or intermediate probability had a D-dimer level below 500 µg L-1 and 653 (41.1%) had a negative D-dimer test according to the age-adjusted cut-off. Using the GS, the figures were 491(30.9%) and 650 (40.9%). None of the patients considered as not having PE based on a low or intermediate SGS and negative D-dimer had a recurrent thromboembolic event during the 3-month follow-up. Conclusions The use of SGS has similar efficiency and safety to the GS in excluding PE in association with the D-dimer test.

One versus two years of elastic compression stockings for prevention of post-thrombotic syndrome (OCTAVIA study): randomised controlled trial.

OBJECTIVE:  To study whether stopping elastic compression stockings (ECS) after 12 months is non-inferior to continuing them for 24 months after proximal deep venous thrombosis. DESIGN:  Multicentre single blind non-inferiority randomised controlled trial. SETTING:  Outpatient clinics in eight teaching hospitals in the Netherlands, including one university medical centre. PARTICIPANTS:  Patients compliant with compression therapy for 12 months after symptomatic, ultrasound proven proximal deep venous thrombosis of the leg. INTERVENTIONS:  Continuation or cessation of ECS 12 months after deep venous thrombosis. MAIN OUTCOME MEASURES:  The primary outcome was the incidence of post-thrombotic syndrome 24 months after diagnosis of deep venous thrombosis, as assessed by the standardised Villalta scale in an intention to treat analysis. The predefined non-inferiority margin was 10%. The main secondary outcome was quality of life (VEINES-QOL/Sym). RESULTS:  518 patients compliant with ECS and free of post-thrombotic syndrome were randomised one year after diagnosis of deep venous thrombosis to stop or continue ECS therapy for another year. In the stop-ECS group, 51 of 256 patients developed post-thrombotic syndrome, with an incidence of 19.9% (95% confidence interval 16% to 24%). In the continue-ECS group, 34 of 262 patients developed post-thrombotic syndrome (incidence 13.0%, 9.9% to 17%), of whom 85% used ECS six or seven days a week during the study period, for an absolute difference of 6.9% (95% confidence interval upper limit 12.3%). Because the upper limit of the 95% confidence interval exceeds the predefined margin of 10%, non-inferiority was not reached. The number needed to treat to prevent one case of post-thrombotic syndrome by continuing ECS was 14 (95% confidence interval lower limit 8). Quality of life did not differ between the two groups. CONCLUSION:  Stopping ECS after one year in compliant patients with proximal deep venous thrombosis seemed not to be non-inferior to continuing ECS therapy for two years in this non-inferiority trial. TRIAL REGISTRATION:  Netherlands Trial Register NTR1442.

Cost-effectiveness of a nurse-led internet-based vascular risk factor management programme: economic evaluation alongside a randomised controlled clinical trial.

OBJECTIVE: To assess the cost-effectiveness of an internet-based, nurse-led vascular risk factor management programme in addition to usual care compared with usual care alone in patients with a clinical manifestation of a vascular disease. DESIGN: Cost-effectiveness analysis alongside a randomised controlled trial (the Internet-based vascular Risk factor Intervention and Self-management (IRIS) study). SETTING: Multicentre trial in a secondary and tertiary healthcare setting. PARTICIPANTS: 330 patients with a recent clinical manifestation of atherosclerosis in the coronary, cerebral, or peripheral arteries and with ≥2 treatable vascular risk factors not at goal. INTERVENTION: The intervention consisted of a personalised website with an overview and actual status of patients' vascular risk factors, and mail communication with a nurse practitioner via the website for 12 months. The intervention combined self-management support, monitoring of disease control and pharmacotherapy. MAIN OUTCOME MEASURES: Societal costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness. RESULTS: Patients experienced equal health benefits, that is, 0.86 vs 0.85 QALY (intervention vs usual care) at 1 year. Adjusting for baseline differences, the incremental QALY difference was -0.014 (95% CI -0.034 to 0.007). The intervention was associated with lower total costs (€4859 vs €5078, difference €219, 95% CI -€2301 to €1825). The probability that the intervention is cost-effective at a threshold value of €20,000/QALY, is 65%. At mean annual cost of €220 per patient, the intervention is relatively cheap. CONCLUSIONS: An internet-based, nurse-led intervention in addition to usual care to improve vascular risk factors in patients with a clinical manifestation of a vascular disease does not result in a QALY gain at 1 year, but has a small effect on vascular risk factors and is associated with lower costs. TRIAL REGISTRATION NUMBER: NCT00785031.

Variable D-dimer thresholds for diagnosis of clinically suspected acute pulmonary embolism.

BACKGROUND: Computed tomography pulmonary angiography (CTPA) is frequently requested using diagnostic algorithms for suspected pulmonary embolism (PE). For suspected deep vein thrombosis, it was recently shown that doubling the D-dimer threshold in patients with low pretest probability safely decreased the number of ultrasonograms. We evaluated the safety and efficiency of a similar strategy in patients with suspected PE. METHODS: We performed a post-hoc analysis of 2213 consecutive patients of two cohort studies with suspected PE who were managed according to current standards: PE ruled out in case of unlikely probability (Wells rule ≤ 4 points) and a D-dimer level < 0.5 µg mL(-1) . CTPA was performed in all other cases. All patients were followed for 3 months. We calculated 3-month venous thromboembolism (VTE) incidence and the number of required CTPAs for selective D-dimer thresholds in patients with low clinical probability (< 2 points, D-dimer threshold < 1.0 µg mL(-1) ) and intermediate probability (2-6 points, D-dimer threshold < 0.5 µg mL(-1) ). RESULTS: Using standard management, PE could be excluded without CTPA in 26% of patients, with a 3-month VTE incidence of 0.88% (95% confidence interval [CI] 0.29-2.1%). Using selective D-dimer thresholds, PE could be excluded without CTPA in 36% of patients, with a 3-month VTE incidence of 2.1% (95% CI 1.2-3.4%) in patients managed without CTPA, an increase of 1.2 percentage points (95% CI -0.3 to 2.2). CONCLUSIONS: Applying selective D-dimer thresholds reduces the need for CTPA by 11 percentage points but is associated with an increased failure rate. Prospective studies should evaluate the safety and net clinical benefit of this approach.

Hestia criteria can safely select patients with pulmonary embolism for outpatient treatment irrespective of right ventricular function.

BACKGROUND: There has been debate over how patients with pulmonary embolism (PE) can be safely selected for outpatient treatment. OBJECTIVES: To compare the Hestia criteria with the European Society of Cardiology (ESC) criteria for selecting low-risk patients with PE for outpatient treatment. METHODS: From 2008 to 2010, 496 patients with acute, symptomatic PE were screened and 275 treated at home and 221 treated in the hospital according to the Hestia Study protocol. The Hestia criteria were used to select patients for outpatient treatment. Right and left ventricular (RV and LV) diameters were measured on computed tomography images. RV dysfunction was defined as an RV/LV ratio > 1.0. Patients were classified according to the ESC criteria into low, intermediate and high-risk groups, based on blood pressure and RV dysfunction. During 3 months follow-up adverse events were scored. RESULTS: Adverse events occurred in 22 patients (4.5%) treated in the hospital vs. none of the patients treated at home (P < 0.001). Sensitivity and negative predictive value for adverse outcome were 100% for the Hestia criteria and 96% and 99% for the ESC criteria, respectively. Of the patients treated at home according to the Hestia criteria, 35% were normotensive but had RV dysfunction and were classified as intermediate risk according to the ESC criteria. No adverse events happened in these patients treated at home. CONCLUSIONS: Clinical criteria, such as the Hestia criteria, could be helpful in selecting patients, including those with RV dysfunction who have a low risk of adverse clinical outcome and could be candidates for outpatient treatment.

Internet based vascular risk factor management for patients with clinically manifest vascular disease: randomised controlled trial.

OBJECTIVE: To investigate whether an internet based, nurse led vascular risk factor management programme promoting self management on top of usual care is more effective than usual care alone in reducing vascular risk factors in patients with clinically manifest vascular disease. DESIGN: Prospective randomised controlled trial. SETTING: Multicentre trial in secondary and tertiary healthcare setting. PARTICIPANTS: 330 patients with a recent clinical manifestation of atherosclerosis in the coronary, cerebral, or peripheral arteries and with at least two treatable risk factors not at goal. INTERVENTION: Personalised website with an overview and actual status of patients' risk factors and mail communication via the website with a nurse practitioner for 12 months; the intervention combined self management support, monitoring of disease control, and drug treatment. MAIN OUTCOME MEASURES: The primary endpoint was the relative change in Framingham heart risk score after 1 year. Secondary endpoints were absolute changes in the levels of risk factors and the differences between groups in the change in proportion of patients reaching treatment goals for each risk factor. RESULTS: Participants' mean age was 59.9 (SD 8.4) years, and most patients (n=246; 75%) were male. After 1 year, the relative change in Framingham heart risk score of the intervention group compared with the usual care group was -14% (95% confidence interval -25% to -2%). At baseline, the Framingham heart risk score was higher in the intervention group than in the usual care group (16.1 (SD 10.6) v 14.0 (10.5)), so the outcome was adjusted for the separate variables of the Framingham heart risk score and for the baseline Framingham heart risk score. This produced a relative change of -12% (-22% to -3%) in Framingham heart risk score for the intervention group compared with the usual care group adjusted for the separate variables of the score and -8% (-18% to 2%) adjusted for the baseline score. Of the individual risk factors, a difference between groups was observed in low density lipoprotein cholesterol (-0.3, -0.5 to -0.1, mmol/L) and smoking (-7.7%, -14.9% to -0.4%). Some other risk factors tended to improve (body mass index, triglycerides, systolic blood pressure, renal function) or tended to worsen (glucose concentration, albuminuria). CONCLUSION: An internet based, nurse led treatment programme on top of usual care for vascular risk factors had a small effect on lowering vascular risk and on lowering of some vascular risk factors in patients with vascular disease. TRIAL REGISTRATION: Clinical trials NCT00785031.

Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study.

BACKGROUND: Traditionally, patients with pulmonary embolism (PE) are initially treated in the hospital with low molecular weight heparin (LMWH). The results of a few small non-randomized studies suggest that, in selected patients with proven PE, outpatient treatment is potentially feasible and safe. OBJECTIVE: To evaluate the efficacy and safety of outpatient treatment according to predefined criteria in patients with acute PE. PATIENTS AND METHODS: A prospective cohort study of patients with objectively proven acute PE was conducted in 12 hospitals in The Netherlands between 2008 and 2010. Patients with acute PE were triaged with the predefined criteria for eligibility for outpatient treatment, with LMWH (nadroparin) followed by vitamin K antagonists. All patients eligible for outpatient treatment were sent home either immediately or within 24 h after PE was objectively diagnosed. Outpatient treatment was evaluated with respect to recurrent venous thromboembolism (VTE), including PE or deep vein thrombosis (DVT), major hemorrhage and total mortality during 3 months of follow-up. RESULTS: Of 297 included patients, who all completed the follow-up, six (2.0%; 95% confidence interval [CI] 0.8-4.3) had recurrent VTE (five PE [1.7%] and one DVT [0.3%]). Three patients (1.0%, 95% CI 0.2-2.9) died during the 3 months of follow-up, none of fatal PE. Two patients had a major bleeding event, one of which was fatal intracranial bleeding (0.7%, 95% CI 0.08-2.4). CONCLUSION: Patients with PE selected for outpatient treatment with predefined criteria can be treated with anticoagulants on an outpatient basis. (Dutch Trial Register No 1319; http://www.trialregister.nl/trialreg/index.asp).

Human CD34+/KDR+ cells are generated from circulating CD34+ cells after immobilization on activated platelets.

OBJECTIVE: The presence of kinase-insert domain-containing receptor (KDR) on circulating CD34+ cells is assumed to be indicative for the potential of these cells to support vascular maintenance and repair. However, in bone marrow and in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood, less than 0.5% of CD34+ cells co-express KDR. Therefore, we studied whether CD34+/KDR+ cells are generated in the peripheral circulation. METHODS AND RESULTS: Using an ex vivo flow model, we show that activated platelets enable CD34+ cells to home to sites of vascular injury and that upon immobilization, KDR is translocated from an endosomal compartment to the cell-surface within 15 minutes. In patients with diabetes mellitus type 2, the percentage of circulating CD34+ co-expressing KDR was significantly elevated compared to age-matched controls. When treated with aspirin, the patients showed a 49% reduction in the generation of CD34+/KDR+ cells, indicating that the level of circulating CD34+/KDR+ cells also relates to in vivo platelet activation. CONCLUSIONS: Circulating CD34+/KDR+ are not mobilized from bone marrow as a predestined endothelial progenitor cell population but are mostly generated from circulating multipotent CD34+ cells at sites of vascular injury. Therefore, the number of circulating CD34+/KDR+ cells may serve as a marker for vascular injury.

Accuracy of carotid plaque detection and intima-media thickness measurement with ultrasonography in routine clinical practice.

BACKGROUND: Current guidelines in cardiovascular disease prevention advocate the use of carotid ultrasound measurements for risk stratification. Carotid abnormalities (plaques or increased intima-media thickness (IMT)) are associated with high risk of coronary and peripheral artery disease. An office-based measurement by clinicians would considerably broaden the clinical applicability of carotid ultrasound. In the present study we have assessed the accuracy of ultrasound detection of carotid plaques and intima-media thickness by trained internists in a routine outpatient setting. METHODS AND RESULTS: Carotid ultrasound was performed in 112 vascular outpatients by internists, after a six-week training period. The internists' results were independently compared to the reference standard, consisting of carotid ultrasound performed in a specialized vascular laboratory. Sensitivity and specificity were calculated for plaque detection and IMT determination. The mean time required to perform the scans on the outpatient department was 7.3 min (range 4.5 to 16.7 min). A high level of accuracy for detecting plaques (sensitivity 78.5%; specificity 93.6%) was achieved. Identifying abnormal IMT had lower sensitivity but adequate specificity of 46.7% and 87.6%, respectively. CONCLUSIONS: In conclusion, our findings demonstrate that clinicians can be trained well enough in six weeks to accurately and efficiently detect carotid plaques in an outpatient setting. IMT abnormalities were less accurately detected in the office-based approach and may require a specialized vascular laboratory.

High D-dimer levels increase the likelihood of pulmonary embolism.

Objective. To determine the utility of high quantitative D-dimer levels in the diagnosis of pulmonary embolism. Methods. D-dimer testing was performed in consecutive patients with suspected pulmonary embolism. We included patients with suspected pulmonary embolism with a high risk for venous thromboembolism, i.e. hospitalized patients, patients older than 80 years, with malignancy or previous surgery. Presence of pulmonary embolism was based on a diagnostic management strategy using a clinical decision rule (CDR), D-dimer testing and computed tomography. Results. A total of 1515 patients were included with an overall pulmonary embolism prevalence of 21%. The pulmonary embolism prevalence was strongly associated with the height of the D-dimer level, and increased fourfold with D-dimer levels greater than 4000 ng mL(-1) compared to levels between 500 and 1000 ng mL(-1). Patients with D-dimer levels higher than 2000 ng mL(-1) and an unlikely CDR had a pulmonary embolism prevalence of 36%. This prevalence is comparable to the pulmonary embolism likely CDR group. When D-dimer levels were above 4000 ng mL(-1), the observed pulmonary embolism prevalence was very high, independent of CDR score. Conclusion. Strongly elevated D-dimer levels substantially increase the likelihood of pulmonary embolism. Whether this should translate into more intensive diagnostic and therapeutic measures in patients with high D-dimer levels irrespective of CDR remains to be studied.

Effects of aspirin on serum C-reactive protein and interleukin-6 levels in patients with type 2 diabetes without cardiovascular disease: a randomized placebo-controlled crossover trial.

AIM: Low-grade inflammation plays a pivotal role in atherogenesis in type 2 diabetes. Next to its antithrombotic effects, several lines of evidence demonstrate anti-inflammatory properties of aspirin. We determined the effects of aspirin on inflammation - represented by C-reactive protein (CRP) and interleukin-6 (IL-6) - in type 2 diabetic subjects without cardiovascular disease and assessed differential effects of aspirin 300 mg compared with 100 mg. METHODS: A randomized, placebo-controlled, double-blind, crossover trial was performed in 40 type 2 diabetic patients. In two periods of 6 weeks, patients used 100 or 300 mg aspirin and placebo. Plasma CRP and IL-6 levels were measured before and after both periods. RESULTS: Use of aspirin resulted in a CRP reduction of 1.23 +/- 1.02 mg/l (mean +/- s.e.m.), whereas use of placebo resulted in a mean increase of 0.04 +/- 1.32 mg/l (P = 0.366). Aspirin reduced IL-6 with 0.7 +/- 0.5 pg/ml, whereas use of placebo resulted in a mean increase of 0.2 +/- 0.8 pg/ml (P = 0.302). There were no significant differences in effects on CRP and IL-6 between 100 and 300 mg aspirin. CONCLUSIONS: Our results indicate that a 6-week course of aspirin does not improve low-grade inflammation in patients with type 2 diabetes without cardiovascular disease, although a modest effect could not be excluded. No significant differential effects between aspirin 100 and 300 mg were found.

Unusual presentation of central nervous system manifestations of Varicella zoster virus vasculopathy in renal transplant recipients.

We describe 2 renal transplant recipients with severe but reversible neurological manifestations related to Varicella zoster virus (VZV) cerebral vasculopathy. To the best of our knowledge, this is the first description of cerebral VZV vasculopathy in solid organ transplant recipients. We review the published literature on the clinical presentation, diagnosis and treatment. In solid organ transplant recipients presenting with neurological signs and symptoms, a diagnosis of VZV-associated vasculopathy should be considered.

Aspirin in the prevention and treatment of venous thromboembolism.

This review summarizes available evidence on effects of aspirin on incidence and outcomes of venous thromboembolism (VTE). From a pathophysiological point of view, inhibition of platelet aggregation is associated with an impaired thrombus formation both in an experimental model of venous thrombosis and in vivo. Epidemiological evidence in support of a beneficial effect of acetylsalicylic acid on VTE incidence is provided by the Antiplatelet Trialists' Collaboration meta-analysis of studies on the use of antiplatelet agents in cardiovascular risk reduction, showing a significant 25% risk reduction of pulmonary embolism. Moreover, a meta-analysis on older trials of antiplatelet agents in postsurgical VTE prevention and the large Pulmonary Embolism Prevention trial demonstrate a protective effect of the same magnitude: 25-30%. However, as low-molecular-weight heparins (LMWH) and vitamin K antagonists (VKA) have shown a superior efficacy and safety profile, and no direct comparisons have been made between aspirin, LMWH and VKA in prolonged use, the most recent guidelines advise against aspirin monotherapy for thromboprophylaxis in the surgical patient. Currently, there is no evidence to support a role for aspirin in air travel-related VTE. Regarding prevention of recurrent VTE, studies are ongoing to determine the potential role of aspirin after a first unprovoked VTE.