Risk Of Recurrent Pulmonary Embolism Research Articles

Long-term anticoagulant therapy in the aspect of secondary prevention of recurrent pulmonary embolism

Aim. To determine differences in laboratory coagulation parameters using routine and integral monitoring methods in patients depending on anticoagulant therapy >12 months after pulmonary embolism (PE) with a high recurrence risk.Material and methods. The study included 72 patients who, according to indications, received long-term anticoagulant therapy >12 months due to a high risk of recurrent thromboembolism. During the follow-up period (15-20 months from the first pulmonary embolism episode), the plasma coagulation parameters were studied using a conventional panel and D-dimer assessment, as well as a thrombin generation test and thrombodynamics. Patients adherent to prolonged anticoagulation were included in group 1. During the collection period, 8 patients independently stopped taking anticoagulants, despite the high risk of recurrent pulmonary embolism (group 2).Results. There were no significant differences in coagulation parameters and D-dimer levels between the studied groups of patients. In the group of patients continuing to take anticoagulants, there was an increase in clot growth delay parameters in comparison with patients of group 2 according to the thrombodynamics results (p=0,046) and the thrombin generation test in platelet-poor plasma in comparison with reference values (p=0,001).Conclusion. Long-term anticoagulant therapy effectively prevents recurrent venous thromboembolism. In patients after primary pulmonary embolism who refuse anticoagulation, the clot growth delay values are shortened, which indicates an increased risk of recurrent venous thromboembolism. The most stable plasma coagulation parameters are observed in patients taking direct oral anticoagulants.

Anticoagulation in chronic thromboembolic pulmonary hypertension: A systematic review and meta-analysis

IntroductionLife-long anticoagulation is the recommended management for chronic thromboembolic pulmonary hypertension (CTEPH). Evidence regarding the use of direct oral anticoagulants (DOAC) for CTEPH is yet to be established. We performed a systematic review and meta-analysis to clarify the outcomes of CTEPH in patients who used DOAC or vitamin K antagonists (VKA). MethodsWe reviewed literature in PubMed and EMBASE through March 2023. We included studies involving patients with CTEPH where DOAC and VKA were compared. We collected data including intervention history for CTEPH, bleeding events, recurrence of VTE (venous thromboembolism), and mortality. We performed a meta-analysis using the Mantel-Haenszel method with a fixed-effects model. ResultsWe included one randomized clinical trial and six observational studies, with a total of 2969 patients. Six studies investigated major bleeding outcomes, and seven investigated all bleeding outcomes. There were no differences in major bleeding (RR 0.59, 95 % CI [0.34–1.02], I2 = 0 %) and all–bleeding (RR 0.87, 95 % CI [0.67–1.13], I2 = 0 %). Based on the five studies we included, DOAC was associated with a lower risk of mortality (RR 0.54, 95 % CI: 0.37–0.79, I2 = 5 %). However, a higher risk of recurrent pulmonary embolism (PE) was seen in three studies (RR 3.80, 95 % CI: [1.93–7.50], I2 = 11 %). No significant differences were noted in terms of VTE. ConclusionDOAC compared to VKA was associated with a significantly lower mortality and higher risk of recurrent PE. Since most of the included studies are observational, we must consider the existence of multiple biases and confounding factors.

(977) Post-Operative Use of Direct Oral Anticoagulants is Associated with Increased Risk of Recurrent Pulmonary Embolism Following Pulmonary Thromboendarterectomy

(977) Post-Operative Use of Direct Oral Anticoagulants is Associated with Increased Risk of Recurrent Pulmonary Embolism Following Pulmonary Thromboendarterectomy

Association of statin use and the risk of recurrent pulmonary embolism in real-world Chinese population.

BackgroundPrevious studies have suggested that statins exert protective effects against venous thromboembolism. However, few randomized studies have explicitly concentrated on patients with pulmonary embolism. Thus far, evidence of the effect of statins on the pulmonary embolism recurrence in China remains lacking.MethodsA retrospective analysis was conducted utilizing our University database. Patients with an International Coding of Diseases-defined diagnosis of pulmonary embolism from 1 January 2017 to 31 December 2019 were included. The patients were divided into two groups, namely, with statin or without statin treatment. Propensity score matching was applied to balance the covariates between the comparison groups. Univariate analysis and multivariable logistic regression were performed to analyze the association between statin use and pulmonary embolism recurrence.ResultsA total of 365 patients diagnosed with pulmonary embolism were included in the research. Pulmonary embolism recurrence accounted for 15.1% of the patients and was observed during the entire study period. In the initial population, no significant difference in recurrence was observed between the groups with and without statins treatment (statin 15.6% vs. non-statin 14.9%, p = 0.860). After propensity score matching, multivariate logistic regression analysis revealed that the odds ratio of pulmonary embolism recurrence in the statin users was 0.489 (95% confidence interval 0.190–1.258, p = 0.138).ConclusionsOur study provides no support for the use of statins as an adjunctive therapy in patients with pulmonary embolism at the initiated time of diagnosis or as a prophylactical plan when anticoagulation is discontinued attempting to reduce the risk of recurrence.

Vena caval filters for the prevention of pulmonary embolism.

Pulmonary emboli (PE), or blood clots in the lungs,can be potentially fatal. Anticoagulation is the first line therapy to prevent PE. In some instances anticoagulation fails to prevent more emboli, or cannot be given because the person has a high risk of bleeding. Inferior vena caval filters (VCFs) are metal alloy devices that mechanically trap fragmented emboli from the deep leg veins en route to the pulmonary circulation. Retrievable filters are designed to be introduced and removed percutaneously. Although their deployment seems of theoretical benefit, their clinical efficacy and adverse event profile is unclear. This is the third update of a Cochrane Review first published in 2007. To assess the evidence for the effectiveness and safety of vena caval filters (VCFs) in preventing pulmonary embolism (PE). For this review update, the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched 10 September 2019) and the Cochrane Register of Controlled Trials (CENTRAL) (2019, Issue 8) via the Cochrane Register of Studies Online. The CIS also searched MEDLINE Ovid, EMBASE Ovid, CINAHL, and AMED (1 January 2017 to 10 September 2019) and trials registries to 10 September 2019. We included randomised controlled trials (RCTs) and controlled clinical trials (CCTs) that examined the efficacy of VCFs in preventing PE. For this update, studies were assessed and data extracted independently. We assessed study quality with Cochrane's 'Risk of bias' tool and used the GRADE approach to assess the overall certainty of the evidence. The outcomes of interest were PE, mortality, lower limb venous thrombosis, filter-related complications and major bleeding. We identified four new studies for this update, bringing the total to six included studies involving 1388 participants. The six studies were clinically heterogeneous and we were unable to carry out meta-analysis. Only two studies were considered to be both applicable in current clinical settings and of good methodological quality. One was a randomised open-label trial studying the effect of a retrievable inferior vena caval filter plus anticoagulation versus anticoagulation alone on risk of recurrent pulmonary embolism (PE) in 399 participants over three months. There was no evidence of a difference in the rates of PE, death, lower extremity deep vein thrombosis (DVT), or bleeding at three and six months after the intervention (moderate-certainty evidence). A filter was inserted in 193 people, but could only be successfully retrieved from 153. Minor filter complications were noted at six months. The second clinically relevant study was a randomised open-label trial of 240 participants who had sustained multiple traumatic injuries, allocated to a filter or no filter, three days after injury, in conjunction with anticoagulation and intermittent pneumatic compression. Prophylactic anticoagulation was initiated in both groups when it was thought safe to do so. There was no evidence of a difference in symptomatic PE, death, or lower limb venous thrombosis rates (moderate-certainty evidence). The only major filter complication was that one person required surgical removal of the filter. We are unable to draw any conclusions from the remaining four included studies. One study showed an increased incidence of long-term lower extremity DVT at eight years. Three studies are no longer clinically applicable because they utilised permanent filters which are seldom used now, or they did not use routine prophylactic anticoagulation which is current standard practice. The fourth study compared two filter types and was terminated prematurely as one filter group had a higher rate of thrombosis compared to the other filter type. Two of the six identified studies were relevant for current clinical settings. One showed no evidence of a benefit of retrievable filters in acute PE for the outcomes of PE, death, DVT and bleeding during the initial three months in people who can receive anticoagulation (moderate-certainty evidence). The other study did not show any benefit for prophylactic filter insertion in people who sustained multiple traumatic injuries, with respect to symptomatic PE, mortality, or lower extremity venous thrombosis (moderate-certainty evidence). We can draw no firm conclusions regarding filter efficacy in the prevention of PE from the remaining four RCTs identified in this review. Further trials are needed to assess vena caval filter effectiveness and safety, and clinical differences between various filter types.

PULMONARY EMBOLISM IN THE SETTING OF THYROID STORM: DURATION OF ANTI-COAGULATION

SESSION TITLE: Fellows Pulmonary Vascular Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Thyroid storm is an uncommon, life-threatening presentation of hyperthyroidism with a high mortality rate. It carries an increased risk for thromboembolic diseases and pulmonary embolism (PE) which leads to increased mortality of this condition. Generally, life-long anticoagulation is used. CASE PRESENTATION: 61-year-old female, with hyperthyroidism and hypertension, presented with 3 days of shortness of breath with minimal exertion and right sided chest pain. She reported fatigue, poor sleep, palpitations, poor appetite, diarrhea, and 20 lb. weight loss. Her physician discontinued her Methimazole due to “normal thyroid tests” one month ago. She had sinus tachycardia (150s) and fever (101.8 F.) in the emergency department. CT of the chest showed bilateral pulmonary emboli (Figure 1). Her blood work demonstrated a leukocytosis with left shift, an undetectable TSH, and a low free T4. She was diagnosed with thyroid storm with a Burch-Wartofsky scale of 50 points (fever, diarrhea, and tachycardia). She began propylthiouracil, propranolol, hydrocortisone, and full dose enoxaparin. Her symptoms improved rapidly. She was switched to Apixaban and Methimazole prior to discharge. She received 3 months of anticoagulation and then chose to stop due to personal preference. The risk of recurrent PE was explained to the patient. She has been off anticoagulation for a year without recurrence. DISCUSSION: Thyroid storm is a rare (0.57-0.76 cases/100,000 US persons per year)1 condition and carries an increased risk for PE. It carries a mortality between 10-20%.2 Treatment is full dose anticoagulation and the duration is usually life-long. If we hypothesize that the hypercoagulable state resolves with the resolution of the hyperthyroid state, then anticoagulation should be safely discontinued. A retrospective case-cohort study by Lin et al. showed that the incidence of incident PE is 2.31 times more common in patients with hyperthyroidism compared to controls after adjustments for several confounders.3 CONCLUSIONS: Thyroid storm and hyperthyroidism are hypercoagulable states. Initial treatment with full dose anticoagulation is needed. However, the risk for thromboembolic events is not well studied after resolution of the hyperthyroid state. To our knowledge, only one retrospective case-cohort study showed an increased risk of thromboembolic disease in a 5-year follow-up period. Based on that study, life-long anticoagulation is warranted but future randomized trials are needed to establish this association and study the best duration of anticoagulation. Reference #1: Galindo RJ, Hurtado CR, Pasquel FJ, et al. National Trends in Incidence, Mortality, and Clinical Outcomes of Patients Hospitalized for Thyrotoxicosis With and Without Thyroid Storm in the United States, 2004-2013. Thyroid. 2019;29(1):36-43. Reference #2: Min, T., Benjamin, S., & Cozma, L. Thromboembolic complications of thyroid storm, Endocrinology, Diabetes & Metabolism Case Reports, 2014. Reference #3: LIN, H.-C., YANG, L.-Y. and KANG, J.-H. (2010), Increased risk of pulmonary embolism among patients with hyperthyroidism: a 5-year follow-up study. Journal of Thrombosis and Haemostasis, 8: 2176-2181. doi:10.1111/j.1538-7836.2010.03993.x DISCLOSURES: No relevant relationships by Cinthya Carrasco Barcenas, source=Web Response No relevant relationships by Amr Ismail, source=Web Response No relevant relationships by John Makram, source=Web Response No relevant relationships by Haneen Mallah, source=Web Response No relevant relationships by Barbara Mantilla, source=Web Response No relevant relationships by Arunee Motes, source=Web Response No relevant relationships by Kenneth Nugent, source=Web Response No relevant relationships by David Sotello Aviles, source=Web Response No relevant relationships by Victor Test, source=Web Response No relevant relationships by Myrian Vinan Vega, source=Web Response

Antithrombotic Treatment of Pulmonary Embolism

The present article addresses clinical challenges associated with the choice of the anticoagulant agent, the definition of the duration of anticoagulant treatment and the assessment of the risk-to-benefit ratio of prolonged anticoagulation for patients with pulmonary embolism (PE).Anticoagulation is performed with unfractionated heparin (UFH) in hemodynamically unstable patients and with low molecular weight heparins (LWMH) or fondaparinux in normotensive patients. In patients with high or intermediate clinical probability of pulmonary embolism, anticoagulation should be initiated without delay while awaiting the results of diagnostic tests. LMWH and fondaparinux are preferred over UFH in the initial anticoagulation of PE since they are associated with a lower risk of bleeding.All patients with PE require therapeutic anticoagulation for at least three months. The current 2019 guidelines of the European Society of Cardiology (ESC) recommend that all eligible patients should be treated with a non-vitamin K antagonist oral anticoagulant (NOAC) in preference to a vitamin K antagonist (VKA). In patients with active cancer, Apixaban, Edoxaban and Rivaroxaban are effective alternatives to treatment with LMWH.The decision on the duration of anticoagulation should consider both, the individual risk of PE recurrence and the individual risk of bleeding. The risk for recurrent PE after discontinuation of treatment is related to the features of the index PE event. While patients with a strong transient risk factor have a low risk of recurrence and anticoagulation can be discontinued after three months, patients with strong persistent risk factor (such as active cancer) have a high risk of recurrence and thus should receive anticoagulant treatment of indefinite duration. Given the favourable safety profile of NOACs (especially if a reduced dosage of Apixaban or Rivaroxaban is initiated after at least six months of therapeutic anticoagulation), extended oral anticoagulation of indefinite duration should be considered for all patients with intermediate risk of recurrence.

MP40: Psychological distress in patients following pulmonary embolism diagnosis

Introduction: Pulmonary embolism (PE) is a treatable condition, with a low mortality rate (of around 1% in those who are diagnosed with the condition). The risk of recurrent PE is well managed with long term anticoagulation. Past literature suggests that patients who are diagnosed with PE can go on to experience existential anxiety and symptoms suggestive of post-traumatic stress disorder (PTSD). This study aimed to evaluate the mental and emotional experiences of PE patients through the lens of PTSD, and the factors involved in psychological distress following a PE diagnosis. Methods: Semi-structured interviews were conducted with PE patients at the Juravinski Hospital thrombosis clinic in Hamilton, Ontario. Interview questions were based on DSM-5 criteria of PTSD and relevant existing literature. The transcripts were analyzed by two researchers based on an approach that considers both the content of patients’ accounts as well as the way that patients choose to interpret and deliver those accounts, to develop major themes associated with psychological distress. Results: A total of 37 patients, ranging from 28 to 85 years of age, were interviewed. The patients’ accounts suggested that the manner in which a PE diagnosis was delivered by an emergency physician was a significant factor in the degree to which they experienced psychological distress. For example, patients reported focusing on words suggesting that they were ‘a ticking time-bomb’ or that ‘a lot of people don't get through this,’ which introduced a degree of panic. A number of patients continued to focus on these words, months or years after their diagnosis. Some feared that they could have recurrent PE which could lead to death. Diagnoses that were delivered calmly with thorough explanations of why a patient experienced PE-related symptoms and how they will be treated, helped to minimize any subsequent anxiety. Patients initially misdiagnosed with an alternative condition in the ED also expressed feelings of anxiety and distress. The presence of physically and mentally distressing symptoms was also a factor which contributed to mental distress and anxiety regarding a PE recurrence. Conclusion: Caution should be taken in the delivery of PE diagnosis in the emergency department. Over-emphasis on the severity and life-threatening nature of PE should be avoided to reduce psychological distress.

Inferior vena cava filters in patients with cancer and venous thromboembolism (VTE) does not improve clinical outcomes: A population-based study

BackgroundThere are few studies that have determined clinical outcomes following inferior vena cava filter (IVCF) insertion in cancer patients hospitalized for acute deep-vein-thrombosis (DVT) or pulmonary embolism (PE). Methods and resultsWe analyzed hospital discharge records of all patients with active cancer who were admitted to a California hospital specifically for acute DVT or PE between 2005 through 2009. Propensity and competing risk methodology were used to determine if IVCF-use lowered either 30-day mortality or the risk of recurrent PE, DVT, and major bleeding within 180days. Among 14,000 patients, an IVCF was placed in 2747 (19.6%), but only 577 (21%) of these IVCF patients had an apparent indication for filter use because of acute bleeding or undergoing major surgery. Data on anticoagulation use was not available. Filter-use provided no reduction in either 30-day mortality (HR=1.12, 95% CI: 0.99–1.26, p=0.08) or the adjusted 180-day risk of subsequent PE (±DVT) (HR=0.81, 95% CI: 0.52–1.27, p=0.36). Filter use was, however, associated with an increase in the adjusted180-day risk of recurrent DVT (HR=2.10, 95% CI: 1.53–2.89, p<0.0001). ConclusionsWe conclude that in this population-based study, approximately 20% of cancer patients with acute VTE received an IVCF, but only 21% of these had an indication for IVCF use. Overall, IVCF use provided neither a short-term survival benefit nor a reduction in risk of recurrent PE, but IVCF use was associated with a higher risk of recurrent DVT.

PULMONARY EMBOLISM: SOME ISSUES OF EPIDEMIOLOGY AND TREATMENT IN CANCER PATIENTS

The risk of pulmonary embolism (PE) in cancer patients is 4–7-fold, compared to other patient categories. PE is the second most frequent cause of death in the first year after cancer diagnosis. PE is diagnosed in 7.5% of patients with malignant brain tumors, in 1 to 25% of those with gastrointestinal tumors, in 4.5 to 17.5% of those with breast cancer and in 4 to 10% of lung cancer patients. The risk of PE is higher with surgical interventions and chemotherapy, as well as in metastatic tumors. In 13% of cases, PE may be the first symptom of cancer manifestation. For prevention and treatment of PE low molecular weight heparin (LMWH) and warfarin are used. The risk of recurrent PE is 2-fold lower with LMWH. The frequency of bleeding with LMWH and warfarin treatment is from 14 to 19%. Placement of a cava filter is indicated only if anticoagulation is inefficient. New oral anticoagulants, which act as selective thrombin or Factor Xa inhibitors, are not used in cancer patients. Thus, diagnostics and treatment of PE is a very urgent problem in oncology that requires new approaches to be looked for.

Oral and inhaled corticosteroid use and risk of recurrent pulmonary embolism

IntroductionChronic inflammatory diseases predispose for development of a first pulmonary embolism (PE). Previous studies showed that corticosteroids, which are the mainstay of treatment for inflammatory diseases, enhance the risk of a first venous thromboembolism. Yet, it is unknown whether corticosteroids also predispose for recurrent events. Therefore, we investigated the association between oral and/or inhaled corticosteroid use and the risk of recurrent PE. MethodsWe performed a nested case-control study using the PHARMO Database. Adult patients who had suffered from a first PE for which vitamin K antagonists were prescribed, were eligible. Of these, 384 patients with recurrent PE were matched to 1030 patients without recurrent PE. ResultsWe showed that oral or inhaled corticosteroids was ever used by 22.7% and 20.6% of patients with recurrent PE, and 23.5% and 21.5% of the patients without recurrent PE. There was an overall association between oral corticosteroid use and the risk of recurrent PE (p=0.02). Current use of oral corticosteroids increased the risk of recurrent PE (OR 3.74; 95% CI 2.04–6.87), whereas past use reduced the risk (OR 0.46; 95% CI 0.28–0.74). A similar pattern was observed for inhaled corticosteroids, although less strong (p=0.10). ConclusionsCurrent use of oral corticosteroids is associated with increased risk of recurrent PE. Whether this increased risk is caused by oral corticosteroids themselves, or by the underlying disease, or both, needs further investigation. Nevertheless, given the frequent use of corticosteroids in clinical practice, clinicians should be aware of this risk.

Effect of a Retrievable Inferior Vena Cava Filter Plus Anticoagulation vs Anticoagulation Alone on Risk of Recurrent Pulmonary Embolism: A Randomized Clinical Trial

In hospitalized patients with acute pulmonary embolism use of a retrievable inferior vena cava filter plus anticoagulation compared with anticoagulation alone does not reduce the risk of symptomatic recurrent pulmonary embolism (PE) at 3 months.

Effect of a Retrievable Inferior Vena Cava Filter Plus Anticoagulation vs Anticoagulation Alone on Risk of Recurrent Pulmonary Embolism

Although retrievable inferior vena cava filters are frequently used in addition to anticoagulation in patients with acute venous thromboembolism, their benefit-risk ratio is unclear. To evaluate the efficacy and safety of retrievable vena cava filters plus anticoagulation vs anticoagulation alone for preventing pulmonary embolism recurrence in patients presenting with acute pulmonary embolism and a high risk of recurrence. Randomized, open-label, blinded end point trial (PREPIC2) with 6-month follow-up conducted from August 2006 to January 2013. Hospitalized patients with acute, symptomatic pulmonary embolism associated with lower-limb vein thrombosis and at least 1 criterion for severity were assigned to retrievable inferior vena cava filter implantation plus anticoagulation (filter group; n = 200) or anticoagulation alone with no filter implantation (control group; n = 199). Initial hospitalization with ambulatory follow-up occurred in 17 French centers. Full-dose anticoagulation for at least 6 months in all patients. Insertion of a retrievable inferior vena cava filter in patients randomized to the filter group. Filter retrieval was planned at 3 months from placement. Primary efficacy outcome was symptomatic recurrent pulmonary embolism at 3 months. Secondary outcomes were recurrent pulmonary embolism at 6 months, symptomatic deep vein thrombosis, major bleeding, death at 3 and 6 months, and filter complications. In the filter group, the filter was successfully inserted in 193 patients and was retrieved as planned in 153 of the 164 patients in whom retrieval was attempted. By 3 months, recurrent pulmonary embolism had occurred in 6 patients (3.0%; all fatal) in the filter group and in 3 patients (1.5%; 2 fatal) in the control group (relative risk with filter, 2.00 [95% CI, 0.51-7.89]; P = .50). Results were similar at 6 months. No difference was observed between the 2 groups regarding the other outcomes. Filter thrombosis occurred in 3 patients. Among hospitalized patients with severe acute pulmonary embolism, the use of a retrievable inferior vena cava filter plus anticoagulation compared with anticoagulation alone did not reduce the risk of symptomatic recurrent pulmonary embolism at 3 months. These findings do not support the use of this type of filter in patients who can be treated with anticoagulation. clinicaltrials.gov Identifier: NCT00457158.

Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis.

Thrombolytic therapy may be beneficial in the treatment of some patients with pulmonary embolism. To date, no analysis has had adequate statistical power to determine whether thrombolytic therapy is associated with improved survival, compared with conventional anticoagulation. To determine mortality benefits and bleeding risks associated with thrombolytic therapy compared with anticoagulation in acute pulmonary embolism, including the subset of hemodynamically stable patients with right ventricular dysfunction (intermediate-risk pulmonary embolism). PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from inception through April 10, 2014. Eligible studies were randomized clinical trials comparing thrombolytic therapy vs anticoagulant therapy in pulmonary embolism patients. Sixteen trials comprising 2115 individuals were identified. Eight trials comprising 1775 patients specified inclusion of patients with intermediate-risk pulmonary embolism. Two reviewers independently extracted trial-level data including number of patients, patient characteristics, duration of follow-up, and outcomes. The primary outcomes were all-cause mortality and major bleeding. Secondary outcomes were risk of recurrent embolism and intracranial hemorrhage (ICH). Peto odds ratio (OR) estimates and associated 95% CIs were calculated using a fixed-effects model. Use of thrombolytics was associated with lower all-cause mortality (OR, 0.53; 95% CI, 0.32-0.88; 2.17% [23/1061] vs 3.89% [41/1054] with anticoagulants; number needed to treat [NNT] = 59) and greater risks of major bleeding (OR, 2.73; 95% CI, 1.91-3.91; 9.24% [98/1061] vs 3.42% [36/1054]; number needed to harm [NNH] = 18) and ICH (OR, 4.63; 95% CI, 1.78-12.04; 1.46% [15/1024] vs 0.19% [2/1019]; NNH = 78). Major bleeding was not significantly increased in patients 65 years and younger (OR, 1.25; 95% CI, 0.50-3.14). Thrombolysis was associated with a lower risk of recurrent pulmonary embolism (OR, 0.40; 95% CI, 0.22-0.74; 1.17% [12/1024] vs 3.04% [31/1019]; NNT = 54). In intermediate-risk pulmonary embolism trials, thrombolysis was associated with lower mortality (OR, 0.48; 95% CI, 0.25-0.92) and more major bleeding events (OR, 3.19; 95% CI, 2.07-4.92). Among patients with pulmonary embolism, including those who were hemodynamically stable with right ventricular dysfunction, thrombolytic therapy was associated with lower rates of all-cause mortality and increased risks of major bleeding and ICH. However, findings may not apply to patients with pulmonary embolism who are hemodynamically stable without right ventricular dysfunction.

Letter to the Editor A 53-year-old woman with thrombocytosis and pulmonary embolism

Letter to the Editor A 53-year-old woman with thrombocytosis and pulmonary embolism

Statin treatment and the risk of recurrent pulmonary embolism

This editorial refers to ‘Statin treatment and the risk of recurrent pulmonary embolism’[†][1], by S. Biere-Rafi et al. , on page 1800 Statin treatment is well established for the primary and secondary prevention of atherothrombotic disease in the coronary and cerebral arterial circulation.1 Cholesterol and in particular LDL-cholesterol (LDL-C) is log linearly associated with risk of fatal and non-fatal myocardial infarction; therefore, not unsurprisingly, the benefit of statins on coronary heart disease (CHD) risk appears to be log-linear, with about a one-fifth to one-quarter lowering of CHD risk per 1 mmol/L lowering of LDL-C.1 Whilst the relationship between the effect of cholesterol and LDL-C on incident stroke is less clear, there is clear evidence that statins reduce stroke by about one-fifth, raising the possibility that the clinical benefit may be unrelated to lowering of LDL-C. Statins block hydroxymethylglutaryl (HMG)-CoA reductase, which is a rate-limiting enzyme not only for the production of cholesterol via the squalene pathway but also for the generation of several isoprenoids such as geranyl geranyl pyrophosphate and farnesyl pyrophosphate which prenylate small molecules such as Rho and Ras involved in particular with inflammatory cell signalling, thus leading to activation of various transcription factors.2 These non-LDL- C-dependent but HMG-CoA-related effects have often been referred to as pleiotropic effects and, whilst readily demonstrated in vitro , the clinical relevance of these effects have never been conclusive. Several observational studies and post-hoc data from randomized controlled trials have suggested a range of benefits on cardiovascular disease and the vascular system, from favourable effects on renal function, to favourable effects on heart failure among those with CHD,3 which appear unrelated to effects on LDL-C. It is not surprising, therefore, that interest has focused on venous thrombo-embolic disease⇓ … [1]: #fn-2

Statin treatment and the risk of recurrent pulmonary embolism

Patients with idiopathic venous thromboembolism (VTE) have a high recurrence risk during and after stopping anticoagulant treatment. Several studies suggest that treatment with statins reduces the incidence of a first episode of VTE, but data on the effects in patients with a previous episode are lacking. We examined the effect of statin therapy on the risk of recurrent pulmonary embolism (PE). Using the PHARMO Record Linkage System, a Dutch population-based registry of pharmacy records linked with hospital discharge records, patients hospitalized with an acute episode of PE were identified between 1998 and 2008. Prescription-based use of statins and vitamin K antagonist (VKA) were identified starting at hospital discharge and during follow-up. The association between statin use (time-varying) and the incidence of recurrences, cardiovascular events, and death was assessed using Cox regression analysis. The mean (standard deviation) age was 61 (17) years. The median (range) duration of VKA treatment after acute PE was 199 (45-3793) days. Twenty-four per cent of the patients (n = 737) had at least one prescription of statins during the follow-up period and the median duration of statin therapy was 1557 (5-4055) days. During a median follow-up of 1529 (1-4155) days, 285 (9.2%) patients experienced a recurrence. Treatment with statins was associated with a reduced risk of recurrent PE [adjusted hazard ratio (HR) 0.50, 95% CI: 0.36-0.70], both during and after stopping VKA treatment. A dose-response relationship was shown for potency, with the largest reduction in those with the most potent statins. Finally, statin treatment also reduced the risk for cardiovascular events and all-cause mortality. Statin treatment decreases the risk of recurrent PE, irrespective of VKA treatment. Treatment with statins may be an attractive alternative for anticoagulant treatment in the long-term treatment of PE.

Aneurisma de veia poplítea: relato de caso e revisão da literatura

Os aneurismas venosos são raros, porém causam complicações tromboembólicas. Na maioria das vezes, são encontrados como achados de exame físico ou de imagem. Os aneurismas sintomáticos de veia poplítea são tratados por reparo cirúrgico, devido ao alto risco de recorrência de embolia pulmonar. A técnica mais utilizada é a aneurismectomia tangencial com venorrafia lateral. Na impossibilidade de se empregar esta técnica, faz-se a ressecção com reconstrução venosa. Os autores relatam o caso de uma paciente com aneurisma de veia poplítea, cujo diâmetro era de 44 mm, submetida à aneurismectomia tangencial e venorrafia lateral, com sucesso.

Patient Outcomes after Acute Pulmonary Embolism: A Pooled Survival Analysis of Different Adverse Events

Conclusion: Within 4 years of acute pulmonary embolism (PE), half the patients will have an additional serious adverse clinical event. Summary: Most articles on acute PE focus on incidence and case fatality rates. There are little data on the long-term fate of the patients. This report, however, does provide a more long-term perspective of the fate of patients with PE. We know that death related to PE occurs in approximately 2% to 6% of patients with a hemodynamically stable PE and in >30% of patients with PE presenting with shock or hemodynamic instability (Chest 2002;121:877-905; Arch Intern Med 2004;164:92-96). About 25% of patients do not survive the first year after the diagnosis of PE, with most deaths relating to cancer or chronic heart disease rather than to PE itself (N Engl J Med 1992; 326:1240-1245). We also know that patients with PE are at risk for recurrent PE, chronic thromboembolic pulmonary hypertension, arterial cardiovascular events, and a new diagnosis of cancer (N Engl J Med 1998;338:1169-73; AMA 2005;293:2352-61). The goal of this study was to assess long-term risk for adverse events after PE. The authors analyzed consecutive patients diagnosed with PE between January 2001 and July 2007. Patients were monitored until July 2008 for occurrence of adverse clinical events, defined as death, symptomatic or recurrent venous thromboembolism, cancer, arterial cardiovascular events, and chronic thromboembolic pulmonary hypertension. Statistical analysis included calculation of hazard ratios (HR) and 95% confidence intervals (CI) for individual end points and a combined end point with adjustments for confounders. There were 308 patients with unprovoked and 558 patients with provoked PE. An additional 334 patients without PE were also studied. Median follow-up was 3.3 years. Patients with unprovoked PE had a lower overall risk for death than patients with provoked PE (HR, 0.59; 95% CI, 0.43-0.82). However, they had a higher risk for non-malignancy-related death (HR, 1.8; 95% CI, 1.3-2.5), recurrent venous thromboembolism (HR, 2.1; 95% CI, 1.3-3.1), cancer (HR, 4.4; 95% CI, 2.0-10), cardiovascular events (HR, 2.6; 95% CI, 1.5-3.8), and chronic thromboembolic pulmonary hypertension (1.5% vs 0%). The fraction of patients with provoked and unprovoked PE without events after 1 year was 70%, decreased to <60% after 2 years, and was <50% after 4 years. In comparison, 85% of patients without PE were free of clinical events after 4 years. Comment: These data are sobering. More than 70% of patients with PE will have had a major clinical event by 4 years after the PE. One is tempted to ascribe the late events to the initial occurrence of the PE, but clearly, a diagnosis of cancer as a late clinical event is not caused by the PE. Nevertheless, the high rate of late adverse events that are potentially related to the initial PE (recurrent PE, recurrent venous thromboembolism, and thromboembolic pulmonary hypertension) argues for better protocols for prevention of PE through individual risk stratification of at-risk patients.

Silent Pulmonary Embolism in Patients with Deep Venous Thrombosis: A Systematic Review

Purpose To determine, by systematic review of the literature, the prevalence of silent pulmonary embolism in patients with deep venous thrombosis. Methods Twenty-eight included published investigations were identified through PubMed. Studies were selected if methods of diagnosis of pulmonary embolism were described; if pulmonary embolism was stated to be asymptomatic; and if raw data were presented. Studies were stratified according to whether silent pulmonary embolism was diagnosed by a high-probability ventilation-perfusion lung scan using criteria from the Prospective Investigation of Pulmonary Embolism Diagnosis, computed tomography pulmonary angiography, or conventional pulmonary angiography (Tier 1), or by lung scans based on non-Prospective Investigation of Pulmonary Embolism Diagnosis criteria (Tier 2). Results Silent pulmonary embolism was diagnosed in 1665 of 5233 patients (32%) with deep venous thrombosis. This is a conservative estimate because many of the investigations used stringent criteria for the diagnosis of pulmonary embolism. The incidence of silent pulmonary embolism was higher with proximal deep venous thrombosis than with distal deep venous thrombosis. Silent pulmonary embolism seemed to increase the risk of recurrent pulmonary embolism: 25 of 488 (5.1%) with silent pulmonary embolism versus 7 of 1093 (0.6%) without silent pulmonary embolism. Conclusion Silent pulmonary embolism sometimes involved central pulmonary arteries. Because approximately one third of patients with deep venous thrombosis have silent pulmonary embolism, routine screening for pulmonary embolism may be advantageous.