The absence of association with baseline residual clot burden and cardiopulmonary exercise capacity is also consistent with the long term follow-up study of patients with pulmonary embolism who had systemic thrombolysis, as no benefit was seen on reported dyspnea or exercise capacity.126. The role of low dose systemic or catheter directed thrombolysis in other patient subgroups is uncertain. The increased use and sensitivity of CTPA has seen an increase in single or multiple pulmonary emboli isolated to the smaller, subsegmental pulmonary arteries.99 Despite this increase, overall pulmonary embolism related mortality has not changed, and this may account for the decrease in case fatality.100101102 The clinical significance of subsegmental pulmonary emboli remains uncertain, and recommendations are extrapolated mainly from historical ventilation-perfusion lung scan trials. The final manuscript of this article was reviewed and approved by one lead patient partner from this group. Unfortunately, the study was not sufficiently powered to compare the apixaban doses with each other. PULMONARY EMBOLISM TREATMENT Treatments for PE aim to prevent the clot from becoming larger, prevent new blood clots from forming, and prevent long-term complications. Thrombolytic therapy for PTE remains controversial but may be indicated in hemodynamically unstable acute PTE. If a pulmonary embolus is large, the case is often described as massive PE. Can the use of clinical probability score and D-dimer testing be optimized for the diagnosis of pulmonary embolism in subgroups of patients such as those with a previous history of pulmonary embolism and pregnant women? In the absence of high quality evidence, the patient’s preference should be considered in such decisions. Duration of anticoagulation should be determined after weighing the risk of recurrent venous thromboembolism against the risk of bleeding, along with the associated morbidity and mortality of each outcome. Major bleeding was the primary safety outcome and occurred with similar frequency in each apixaban group (hazard ratio 0.25 (0.03 to 2.24) for apixaban 5 mg versus placebo and 0.49 (0.09 to 2.64) for apixaban 2.5 mg versus placebo). A … Determination of clinically relevant drug interactions is complex in patients with cancer, as they are often treated with many anticancer therapies that may compete for a common metabolic pathway. We included clinical practice guidelines (American College of Chest Physicians, American Society of Hematology, and European Society of Cardiology), as well as screening them to identify additional studies. The choice of long term anticoagulant can include LMWH, edoxaban, or rivaroxaban over VKAs, which are inferior to LMWH. Baseline residual pulmonary obstruction was not associated with the exercise limitation, and nor were pulmonary function testing or echocardiographic results.155 Predictors of exercise limitations were age, body mass index, and smoking history. This approach has been studied in an RCT of 59 patients with acute pulmonary embolism without evidence of hemodynamic compromise on presentation, and CDT showed a benefit in the primary outcome of improved right ventricular function (right ventricular/left ventricular ratio) at 24 hours (mean difference 0.30 (SD 0.20) versus 0.03 (0.16), heparin and CDT respectively; P<0.001).127 Cohort and registry studies have shown improvement in surrogate outcomes of right ventricular function but no difference in recurrent pulmonary embolism or mortality.15 Major bleeding rates are variable across studies but reported by some to be similar to those with systemic thrombolysis.128129 The role for CTD remains unclear, and we do not recommend its routine use except in experienced centers when a patient has hemodynamic compromise and a high risk of bleeding and therapy can be started without delay. To ensure that the benefit of continuing anticoagulation outweighs the potential harm of bleeding, we suggest that the decision to continue anticoagulation should be regularly reassessed. Symptomatic or incidental pulmonary embolisms have similar high risk for recurrence.111 Major bleeding complications are also more common with venous thromboembolism in patients with cancer.112113 Treatment of acute symptomatic and incidental pulmonary embolism is individualized according to risk of recurrent pulmonary embolism and bleeding. Risk stratification for patients with unprovoked venous thromboembolism may also help to determine the risk of recurrent thrombosis. 2020 Oct 20;82(10):1421-1427. doi: 10.1292/jvms.20-0226. VKAs may be used if LMWH or DOACs are unavailable or contraindicated, such as with severe renal impairment or drug-drug interactions. Pulmonary embolism and pregnancy. Acute massive pulmonary embolism after cardiac surgery is very rare. The technique and diagnostic criteria for reporting SPECT ventilation-perfusion scans are variable and have not been validated sufficently.16 On this basis, we suggest favoring planar ventilation-perfusion lung scans over SPECT. If a pulmonary embolism is life-threatening, or if other treatments aren’t effective, your doctor may recommend: Surgery to remove the embolus from the pulmonary artery. An RCT comparing rivaroxaban and apixaban for patients with acute venous thromboembolism is ongoing (NCT03266783), evaluating the differences in clinically relevant bleeding with these anticoagulants. Tinzaparin ou Heparin Standard: Evaluation dans l’Embolie Pulmonaire Study. The observed reduced cardiopulmonary exercise capacity correlated well with several quality of life measurements and the six minute walk test. The primary safety outcome of major bleeding was not different for either dose of rivaroxaban compared with aspirin (hazard ratio 2.01 (0.50 to 8.04) for rivaroxaban 20 mg compared with aspirin and 1.64 (0.39 to 6.84) for rivaroxaban 10 mg compared with aspirin). Prognostic markers of recurrent venous thromboembolism include male sex, advanced age,137138 inherited thrombophilia,70 obesity,70 persistently positive D-dimer,77139 and residual pulmonary obstruction on ventilation-perfusion lung scan.140 Individually, these risk factors are insufficient to recommend long term anticoagulation; however, risk prediction models incorporating various combinations have been proposed.137138 The largest prospectively validated (2785 patients) clinical decision rule is the “Men Continue and HERDOO-2.”75141 In the derivation cohort of this prediction rule, stratifying men into high and low risk categories was not possible; men had an annual risk of recurrent venous thromboembolism of 13.9% (10.8% to 17.0%) while off anticoagulation, so they remained on anticoagulation in the validation cohort. IVC filters were first introduced in 1973 and designed to mechanically trap venous emboli from the lower extremities to prevent pulmonary embolism.122 Since this time, the use of IVC filters has dramatically increased, despite a lack of evidence for an effect on venous thromboembolism related mortality.132 Guidelines from major clinical societies differ in their suggested indication for IVC filters but generally agree on their use in patients with an acute proximal DVT or pulmonary embolism and a contraindication to anticoagulation.122 The use of IVC filters for other indications, such as failure of anticoagulation, massive pulmonary embolism clot burden with residual DVT, severe cardiopulmonary disease, use before thrombolysis, or prophylaxis in patients at high risk, has expanded greatly in recent years but is not driven by evidence.122133, Pre-emptive placement of a permanent IVC filter in addition to standard anticoagulation in patients at high risk with acute proximal DVT was investigated in the Prévention du Risque d’Embolie Pulmonaire par Interruption Cave (PREPIC) study, an RCT of 400 patients, which showed a reduction in the primary outcome of early pulmonary embolism diagnosed within the first 12 days (odds ratio 0.22, 0.05 to 0.90) but no difference in mortality (odds ratio 0.99, 0.29 to 3.42).134 Longer term follow-up data showed similar results, with reduction of pulmonary embolism in the IVC filter arm but a significant increase in recurrent DVT and no difference in overall mortality.47 A follow-up RCT, PREPIC-2, studied removable IVC filters in 399 patients with high risk pulmonary embolism and showed no benefit in the use of the filter combined with standard anticoagulation compared with anticoagulation alone on the primary outcome of recurrent pulmonary embolism at three months (relative risk 2.00, 0.51 to 7.89; P=0.50).135 We suggest that IVC filters should be restricted to patients with an acute proximal DVT or pulmonary embolism in whom full dose anticoagulation cannot be given because of uncontrollable active bleeding or a high risk for life threatening bleeding (for example, coagulation defect, severe thrombocytopenia, recent intracerebral hemorrhage, or cerebral lesion at high risk of bleeding) or urgent surgery requiring interruption of anticoagulation. 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