Recent Updates and Debates in PE Care David Kirk 1/22/2015

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Triage Massive / Shock -> Thrombolysis Submassive No RV strain -> Routine Anticoagulation

Massive PEs Need thrombolysis.

(CHEST 2002; 121:877–905)

“Golden Hour” “In fatal cases, it has long been recognized that two thirds of those patients will die within 1 h of presentation and that anatomically massive PE will only account for one half of those deaths, with the remainder attributed to smaller submassive or recurrent emboli.” (CHEST 2002; 121:877–905)

PE with Shock Should receive immediate systemic thrombolysis unless contraindications. Patients with contraindications or treatment failure should have risks/benefits weighed for catheter-directed tPA or other salvage therapies. ACCP guidelines. http://journal.publications.chestnet.org/issue.aspx?journalid=99&issueid=23443&direction=P

At risk of needing thrombolysis Submassive PEs At risk of needing thrombolysis

(CHEST 2002; 121:877–905)

Systemic Thrombolysis for Submassive PE Unlikely (conflicting) mortality benefit More bleeding including ICH Less decompensation PEITHO - n engl j med 370;15 nejm.org april 10, 2014 Journal of Thrombosis and Haemostasis, 10: 751–759 (higher death) JAMA. 2014;311(23):2414-2421. doi:10.1001/jama.2014.5990 (lower death)

Death may decide when doctors disagree

Judgment in Submassive PEs “…thrombolytic therapy in this population should be individualized and benefits and risks (of bleeding) should be carefully weighed on a case- by-case basis.” Tapson. Uptodate.

Submassive Treatment Anticoagulation with LMWH vs heparin and careful observation is primary treatment. Decompensation Thrombolysis should be used as primary rescue. Catheter-directed therapy should only be considered in patients with contraindications to systemic lytics. ESC PE Guidelines 2014. European Heart Journal (2014) 35, 3033–3080

Who Goes to ICU? Need or high potential need for thrombolysis Shock Altered mental status Severe RV dysfunction Severe hypoxemia Other factors to weigh… Cancer Increased levels of BNP or troponins Severity of RV dysfunction Comorbidities

PESI / sPESI ESC PE Guidelines 2014. European Heart Journal (2014) 35, 3033–3080

Low Risk PEs LMWH over heparin Routine use of IVC filters is not recommended. Coumadin with goal INR of 2.5 for at least 3 months. Most novel anticoagulants for chronic therapy are probably okay. In patients with cancer consider treatment with LMWH for at least 3-6 months and extended anticoagulation until cancer is cured. ESC PE Guidelines 2014. European Heart Journal (2014) 35, 3033–3080

Outpatient Treatment of PEs Probably safe to send home from ER or early discharge under the following conditions: No cancer No history of chronic lung or cardiac disease Pulse less than 110 Systolic BP > 100 Saturation > 90% Reliable outpatient care and access to anticoagulation ESC PE Guidelines 2014. European Heart Journal (2014) 35, 3033–3080

PESI / sPESI ESC PE Guidelines 2014. European Heart Journal (2014) 35, 3033–3080

Current Best Resources ACCP Antithrombotic Guidelines, 9th Edition (2012) 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism.

Catheter-Directed Thrombolysis

Parallels (http://digiphotomag.com/articles/many-traveled-roads-an-interview-with-harvey-stein/)

Parallels Catheter-directed treatment of CVAs / DVTs Cather-directed treatment of PEs

“No Better Than IV tPA”

But wait! MR CLEAN 13.5% increase in functional independence without changes in mortality or symptomatic ICH. More specific therapies and patients: New stents Proximal arterial occlusion 90% failed systemic thrombolysis N Engl J Med 2015;372:11-20. DOI: 10.1056/NEJMoa1411587

Too Slow “The time from symptom onset to endovascular treatment start was too long (1-3 hours) and this delay places [intra- arterial therapy] at a significant disadvantage.” Barreto, Endovascular Therapy for Acute Ischemic Stroke -- An Update

CVA Parallel “We did have one patient several years ago who was sent to the cath lab and did not receive IV t- PA when she was a candidate.”

DVT Parallel Catheter-directed treatment of DVT versus anticoagulation Mortality unchanged Blood transfusions, PEs, ICH, length of stay, and IVC filter placements all significantly higher Three times more hospital charges (http://archinte.jamanetwork.com/article.aspx?articleID=1889011)

ULTIMA Nonblinded, industry-involved trial 59 patients (out of 304 screened) Ultrasound Catheter TPA up to 4hrs vs heparin Required RV/LV ratio > 1.0 Not powered for survival or bleeding complications. RV/LV ratio improved faster with intervention Heparin group “caught up” by 90 days

Natural PE Course “Most patients with PE treated with anti-coagulation alone will achieve embolus resolution at 4 weeks.” “The feared consequence of resultant chronic thromboembolic pulmonary hypertension occurs only 0.1% to 3.8% of patients with PE” “Mortality after submassive PE is uncommon” (Circulation. 2014;129:420-421)

ULTIMAtely Meh? Small, not blinded, industry-involved ULTIMA shows that US facilitated tPA compared to heparin rapidly improves RV size. IVC / RV improvement not significantly different at 90 days. No survival or bleeding data

Seattle-II Industry-funded, not (yet?) published US Catheter directed TPA No comparison group No ICH. Major bleeding 11.3% Many patients required two catheters. RV/LV ratio acutely improved 1 death due to PE (0.5%). 3 total deaths (2%). http://www.medscape.com/viewarticle/823571#

Seattle Pee-eww? Industry-funded. Not published. No comparison group. Although no ICH reported, major bleeding appears as high as systemic tPA. 11.3% vs 11.5%. Apparently only shows short-term RV improvement.

Chronic thromboembolic pulmonary hypertension? 40% never diagnosed with DVT or PE 0.57% incidence in patient’s with PE Only 10/170 (5.8%) with symptoms actually have CTEPH “Because of the very low incidence of CTEPH after PE, the implementation of extensive follow-up programs for the detection of CTEPH after acute PE seems to be unnecessary.” Haematologica. Jun 2010; 95(6): 970–975.

Chronic RV Dysfunction? 159 heparin vs 19 TPA Neither 6 minute walks nor NYHA scores were significantly different between heparin and thrombolysis. RV hypokinesis no difference between the two groups (7% vs 6%) Subgroup analysis showed that in heparin only group 27% had “increase in RVSP” and 46% had symptoms. However, more tPA patients had RVSP > 40 (11% vs 7%). (Chest / 136 / 5 / November, 2009)

ACCP Guidelines “In patients with acute PE when a thrombolytic agent is used, we suggest administration through a peripheral vein over a pulmonary artery catheter.” “In patients with acute PE associated with hypotension and who have (i) contraindications to thrombolysis, (ii) failed thrombolysis, or (iii) shock that is likely to cause death before systemic thrombolysis can take effect (eg, within hours), if appropriate expertise and resources are available, we suggest catheter-assisted thrombus removal over no such intervention.” “In patients with acute PE who are treated with anticoagulants, we recommend against the use of an IVC filter.” http://journal.publications.chestnet.org/issue.aspx?journalid=99&issueid=23443&direction=P

Conclusions Our history with CVAs should be a lesson to us. Despite initial promising studies, most trials of catheter-directed therapy have shown no benefit over standard of care.

Conclusions Although catheter directed thrombolysis for submassive PEs may show some promise, these early industry-supported studies have shown no meaningful long term improvement over routine care. Catheter-directed thrombolysis should remain an option in patients who have contraindications or fail systemic therapy.