Treatment Of Submassive Pulmonary Embolism Research Articles

Catheter-Directed Treatment of Submassive Pulmonary Embolism—A Cautious Step Closer?

Catheter-Directed Treatment of Submassive Pulmonary Embolism—A Cautious Step Closer?

Repeat angiography in patients undergoing conventional catheter-directed thrombolysis for submassive pulmonary embolism: a large single-center experience

Purpose Few studies have examined conventional catheter directed thrombolysis (CDT) for the treatment of submassive pulmonary embolism (PE). Moreover, angiographic resolution of thrombus burden following CDT has infrequently been characterized. This study describes a single-center experience treating submassive PE with CDT while utilizing repeat angiography to determine treatment efficacy. Methods A retrospective analysis of 140 consecutive patients who underwent CDT for submassive PE from December 2012 to June 2019 was performed. Angiographic resolution of thrombus burden after CDT was reported as high (>75%), moderate (51-75%), low (26-50%), or insignificant (≤25%). All angiograms were reviewed by two interventional radiologists. Secondary endpoints included reduction in pulmonary artery pressure (PAP) and clinical outcomes. Bleeding events were classified according to the Society of Interventional Radiology (SIR) adverse event criteria. Results CDT was performed in 140 patients with a mean rtPA dose of 25.3 mg and a mean treatment time of 26.0 hours. Angiographic resolution of thrombus burden was high in 70.0%, moderate in 19.3%, low in 5.7%, and insignificant in 3.6%; in 2 patients (1.4%) repeat angiography was not performed. Systolic PAP was reduced (47 vs. 35 mmHg, p Conclusion In patients with submassive PE undergoing CDT, angiographic resolution of thrombus burden is a safe and directly observable metric that can be used to determine procedural success. In this study, CDT with repeat angiography was associated with a 5.7% bleeding event rate and thirty-day mortality of 1.4%.

Catheter-directed Thrombolysis versus Systemic Anticoagulation for Submassive Pulmonary Embolism: A Meta-Analysis.

The optimal therapy for submassive pulmonary embolism remains in question. The following meta-analysis compiles the current evidence comparing Catheter-Directed Thrombolysis (CDT) versus Systemic Anticoagulation (SA). An electronic search through PubMed and Google scholar revealed studies comparing CDT versus SA in terms of mortality and major bleeding events. Thirty-day, 90-day, and one-year mortality results were analyzed. Six studies were included in the meta-analysis. Thirty-day and one-year mortality were less with CDT compared to SA (OR 0.27 [CI 0.11-0.67]; and OR 0.50 [CI 0.28-0.89]). Ninety-day mortality was similar between the two methods (OR 0.57 [CI 0.17-1.92]). Compilation of all studies reporting at least greater than 30-day mortality revealed less mortality with CDT (OR 0.51 [0.30-0.86]). Major bleeding was similar between the two treatments (OR 1.63 [CI 0.63-4.20]). CDT has less 30-day and 1-year mortality with equivalent rates of major bleeding compared to SA for treatment of submassive pulmonary embolism.

THE CLOT THICKENS: AN OBSERVATIONAL RETROSPECTIVE ANALYSIS OF STANDARD OF CARE VS CATHETER-DIRECTED THERAPY FOR SADDLE PULMONARY EMBOLISM

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Catheter directed therapy (CDT) has garnered increased interest in the treatment of submassive pulmonary embolism (PE) given its potential for rapidly reducing right heart strain (RHS) and clot burden. Our aim was to compare outcomes between standard of care (SC) and CDT in the management of submassive saddle PE. METHODS: In this retrospective analysis, patient chart review was performed on patients diagnosed with a submassive PE and subsequently treated with either SC or CDT. Submassive PE was characterized as those with evidence of RHS on either echocardiogram or CT, but without sustained hypotension (systolic BP <90mmHg). SC entailed treatment with systemic anticoagulation. Treatment with CDT involved a 2mg alteplase (tPA) bolus into each branch of the pulmonary artery (PA) followed by an infusion of the same for a maximum of 24 hours. tPA was discontinued when the mean PA pressure fell below 25mmHg with subsequent transition to systemic anticoagulation. Data was analyzed via chi-square analysis or Mann-Whitney U test for categorical or continuous variables, respectively, using SAS and GraphPad version 8. Statistical significance was determined with p < 0.05 RESULTS: A total of 39 patients diagnosed with saddle PE were treated with either CDT (n = 16) or SC (n = 23) in the period of August 2017 to December 2019. Mean Pulmonary Embolism Severity Index (PESI) score was 112.62 ± 55.61 vs 89.87 ± 26.05 in the CDT vs SC groups, respectively (p = 0.44). 5/16 patients in the CDT arm, compared to 1/23, presented with syncope (p = 0.02). PA pressure at presentation was 62.1 ± 16.14 mmHg and 55.63 ± 11.33 mmHg in the CDT vs SC groups, respectively (p = 0.44). 87.5% in the CDT arm demonstrated right heart strain by ECHO, versus 60.86% in SC arm (p = 0.07). In terms of outcomes, mean length of stay was 5.88 days in the CDT group vs 5 days in the SC group (p = 0.14). No inpatient deaths occurred in either group. Mean PA pressure measured at 3 months in the CDT arm was 26.86 ± 6.59 mmHg vs. 28.38 ± 10.24 mmHg in the CDT vs SC groups, respectively (p = 0.96), while mortality was 0% and 6.67%, respectively (p = 0.46). CONCLUSIONS: There was no statistical significance in both mortality and inpatient survival in patients treated with CDT vs SC. The same was demonstrated in terms of presentation and parameters of severity between the CDT and SC arms, aside from an increased incidence of syncope on presentation in the CDT arm. A limitation of our study was the small cohort of patients involved, which prevents extrapolation of data in a generalized manner. A prospective, randomized trial is required to confirm our results. CLINICAL IMPLICATIONS: Saddle PE tends to have the connotation of requiring more aggressive intervention, such as CDT. Although CDT has been shown to be a safe and effective option, it may not necessarily be the best strategy. Clinical judgment, however, should ultimately prevail in guiding therapy. DISCLOSURES: No relevant relationships by Timmy Li, source=Web Response No relevant relationships by Akhilesh Mahajan, source=Web Response No relevant relationships by Anu Menon, source=Web Response No relevant relationships by Bushra Mina, source=Web Response No relevant relationships by Varun Shah, source=Web Response No relevant relationships by Muhammad Shoaib, source=Web Response

Feasibility of ultrasound-assisted catheter-directed thrombolysis for submassive pulmonary embolism: A meta-analysis of case series.

During the past few years, there has been a surge in the use of ultrasound-assisted catheter-directed thrombolysis (UACDT) for submassive pulmonary embolism (SPE). However, few studies evaluated the feasibility of UACDT for SPE. To evaluate the feasibility of UACDT in treating SPE. A comprehensive search of online databases was performed. Search terms UACDT in SPE were entered into PubMed, Embase, Scopus and the Cochrane Library to identify related articles published until October 2018. A quality assessment and data extraction were performed by two researchers. Meta-analysis was performed using R statistical software. Twelve studies with 485 patients were included in this meta-analysis. The pooled right ventricular/left ventricular ratio decrease and pulmonary artery systolic pressure drop after treatment was -0.34 (95% CI: -0.43, -0.25) and -15.05 (95% CI: -18.10, -12.00) mm Hg, respectively. The pooled major bleeding rate was 1.0% (95% CI: 0.0%, 3.0%), and the in-hospital mortality was 0.0% (95% CI: 0.0%, 1.0%). This up to data meta-analysis confirms that UACDT is a feasible treatment for SPE.

SUCCESSFUL TREATMENT OF PULMONARY EMBOLISM AND ASSOCIATED UPPER EXTREMITY ARTERY THROMBOSIS USING INTRAVENOUS ALTEPLASE: A CASE REPORT

Introduction: Although thrombolytic administration is inevitable in the management of massive pulmonary embolism, contradictions exist in the treatment of sub-massive pulmonary embolism. There are drawbacks to thrombolytic treatment due to potential serious side effects such as cranial hemorrhage. Case Report: An 84-year-old female patient was admitted to the emergency service because of pain and lack of a pulse in her right arm and %61 oxygen saturation without any respiratory system complaints. A computerized tomography showed pulmonary embolism close to totality in the bilateral main pulmonary arteries and peripheral embolism in the right brachial artery. We considered a sub-massive pulmonary embolism in this patient with no hypotension despite bilateral pulmonary artery embolism, good general condition, but a dilated right ventriculi in transthoracic echocardiography. Since the PESI score was 115, it was decided that the patient was in the high-risk group. After administration of 100 mg Alteplase as thrombolytic therapy, her oxygen saturation increased to 95% in the room air and her complaint of right arm completely regressed. Furthermore, none of the possible complications from thrombolytic therapy, such as fatal bleeding, were observed in our patient. Conclusion: In this article, it is emphasized that thrombolytic therapy is an appropriate choice for patients with sub-massive pulmonary embolism and acute arterial embolism.

ULTRASOUND-ASSISTED CATHETER-DIRECTED THROMBOLYSIS: THE EXPERIENCE OF A TERTIARY CARE MEDICAL CENTER

Ultrasound-assisted catheter-directed thrombolysis (USAT) is an emerging therapy for the treatment of submassive pulmonary embolism (PE). We assessed the hypothesis that while USAT is typically delivered safely, older patients with multiple comorbidities may not be selected for therapy despite

Low-dose systemic thrombolytic therapy for treatment of submassive pulmonary embolism: Clinical efficacy but attendant hemorrhagic risks.

The purpose of the present study is to evaluate the safety and efficacy of "low-dose" systemic thrombolytic therapy (TT) for treatment of patients with intermediate-high risk submassive pulmonary embolism (PE). TT is increasingly utilized in acute submassive PE. Strategies for TT include catheter-directed administration as well as traditional IV systemic therapy. Regardless of the route, most studies document the attendant significant bleeding complication rates expected from induction of a systemic lytic state. To mitigate bleeding, "low-dose" systemic TT (Alteplase 50 mg) has been advocated, based on recent studies which demonstrated clinical efficacy with elimination of any significant bleeding complications. Over a 24-month period, our institutional PE Response Team treated 45 acute submassive PE patients with "Low Dose" IV Alteplase 50 mg. Clinical outcomes and bleeding complications were assessed. Overall clinical outcome was excellent, with 97.8% of patients surviving to discharge and a 30-day, all-cause mortality of 4.4%. Despite no patients having a HAS-BLED score > 2 (average score = 0.8 +/-), ISTH major and GUSTO moderate bleeding was observed in 11% (n = 5) of cases. The present observations document that low-dose systemic TT is associated with excellent clinical outcome for intermediate-high risk submassive PE, but with attendant risk for bleeding. These findings are consistent with the concept that induction of a therapeutic lytic state carries inextricable bleeding risk.

Low-dose, short course alteplase treatment of submassive pulmonary embolism: a case series from the National Institutes of Health Clinical Center.

: Guidelines-recommend thrombolytic therapy for pulmonary embolism in patients with severe hemodynamic compromise and low risk of bleeding. Thrombolytics in submassive pulmonary embolism have an unfavorable risk/benefit ratio and remain controversial. Based on our experience with extensive, lower extremity thrombi, nine patients with symptomatic, submassive pulmonary embolisms (five medical, four surgical) were treated with low-dose alteplase (<10 mg/day, infused over 6 h per treatment). Alteplase was delivered by pulse spray and/or directed or undirected central venous catheters depending on clot size and location. All patients improved symptomatically and as determined objectively by pulmonary artery pressures and/or imaging, though acute benefits ranged from substantial to modest. One surgical patient required re-exploration for bleeding at the site of a recent retroperitoneal lymph node dissection. This experience may help guide the design of a randomized controlled trial to determine the safety and efficacy of low-dose alteplase for submassive pulmonary embolism.

Surgical pulmonary embolectomy and catheter-directed thrombolysis for treatment of submassive pulmonary embolism.

Acute pulmonary embolism (PE) with preserved hemodynamics but right ventricular dysfunction, classified as submassive PE, carries a high risk of mortality. We report the results for patients who did not qualify for medical therapy and required treatment of submassive PE with surgical pulmonary embolectomy and catheter-directed thrombolysis (CDT). Between October 1999 and May 2015, 133 submassive PE patients underwent treatment with pulmonary embolectomy (71) and CDT (62). A multidisciplinary PE response team helped to determine the most appropriate treatment strategy on a case-by-case basis. The EkoSonic ultrasound-facilitated thrombolysis system (EKOS) was used for CDT, which was introduced in 2010. The mean age of submassive PE patients was 57.3 years, which included 36.8% females. PE risk factors included previous deep venous thrombosis (46.6%), immobility (36.1%), recent surgery (30.8%), and cancer (22.6%), P < 0.05. The most common indication for advanced treatment was right ventricular strain (42.9%), P = 0.03. The frequency of surgical pulmonary embolectomy remained stable even after incorporating the EKOS procedure into our treatment algorithm, with statistically similar operative mortality. Bleeding was observed in six CDT patients and one pulmonary embolectomy patient (P < 0.05). Follow-up echocardiography was available for 61% of the overall cohort, of whom 76.5% had no residual moderate or severe right ventricular dysfunction. Pulmonary embolectomy and CDT are important contemporary advanced treatment options for selected high-risk patients with submassive PE, who do not qualify for medical therapy.

Minimally Invasive Surgical Pulmonary Embolectomy: A Potential Alternative to Conventional Sternotomy.

Surgical pulmonary embolectomy has gained increasing popularity over the past decade with multiple series reporting excellent outcomes in the treatment of submassive pulmonary embolism. However, a significant barrier to the broader adoption of surgical pulmonary embolectomy remains the large incision and long recovery after a full sternotomy. We report the safety and efficacy of using a minimally invasive approach to surgical pulmonary embolectomy. All consecutive patients undergoing surgical pulmonary embolectomy for a submassive pulmonary embolism (2015-2017) were reviewed. Patients were stratified as conventional or minimally invasive. The minimally invasive approach included a 5- to 7-cm skin incision with upper hemisternotomy to the third intercostal space. The primary outcomes were in-hospital and 90-day survival. Thirty patients (conventional = 20, minimally invasive = 10) were identified. Operative time was similar between the two groups, but cardiopulmonary bypass time was significantly longer in the minimally invasive group (58 vs 94 minutes, P = 0.04). While ventilator time and intensive care unit length of stay were similar between groups, hospital length of stay was 4.5 days shorter in the minimally invasive group, and there was a trend toward less blood product use. In-hospital and 90-day survival was 100%. Within the minimally invasive cohort, median right ventricular dysfunction at discharge was none-mild and no patient experienced postoperative renal failure, deep sternal wound infection, sepsis, or stroke. Minimally invasive surgical pulmonary embolectomy appears to be a feasible approach in the treatment of patients with a submassive pulmonary embolism. A larger, prospective analysis comparing this modality with conventional surgical pulmonary embolectomy may be warranted.

Echocardiographic assessment with right ventricular function improvement following ultrasound-accelerated catheter-directed thrombolytic therapy in submassive pulmonary embolism

Introduction The objective of this study was to evaluate the efficacy of ultrasound-accelerated catheter-directed thrombolytic therapy in patients with submassive pulmonary embolism. Methods Clinical records of 46 patients with submassive pulmonary embolism who underwent ultrasound-accelerated catheter-directed pulmonary thrombolysis using tissue plasminogen activator, from 2007 to 2017, were analyzed. All patients experienced clinical symptoms with computed tomography evidence of pulmonary thrombus burden. Right ventricular dysfunction was present in all patients by echocardiographic finding of right ventricle-to-left ventricle ratio > 0.9. Treatment outcome, procedural complications, right ventricular pressures, and thrombus clearance were evaluated. Follow-up evaluation included echocardiographic assessment of right ventricle-to-left ventricle ratio at one month, six months, and one year. Results Technical success was achieved in all patients ( n = 46, 100%). Our patients received an average of 18.4 ± 4.7 mg of tissue plasminogen activator using ultrasound-accelerated thrombolytic catheter with an average infusion time of 16.5± 5.4 h. Clinical success was achieved in all patients (100%). Significant reduction of mean pulmonary artery pressure occurred following the treatment, which decreased from 36 ± 8 to 21 ± 5 mmHg ( p < 0.001). There were no major bleeding complications. All-cause mortality at 30 days was 0%. No patient developed recurrent pulmonary embolism during follow-up. During the follow-up period, 43 patients (93%) showed improvement of right ventricular dysfunction based on echocardiographic assessment. The right ventricle-to-left ventricle ratio decreased from 1.32 ± 0.18 to 0.91 ± 0.13 at the time of hospital discharge ( p < 0.01). The right ventricular function remained improved at 6 months and 12 months of follow-up, as right ventricle-to-left ventricle ratio were 0.92 ± 0.14 ( p < 0.01) and 0.91 ± 0.15 ( p < 0.01), respectively. Conclusion Ultrasound-accelerated catheter-directed thrombolysis is a safe and efficacious treatment for submassive pulmonary embolism. It reduces pulmonary hypertension and improves right ventricular function in patients with submassive pulmonary embolism.

Catheter-directed therapy as a treatment for submassive pulmonary embolism: A meta-analysis

AimsCatheter-directed therapy (CDT) is included in the guidelines for diagnosing and treating massive pulmonary embolism. However, few studies have evaluated the efficacy of CDT as a treatment for submassive pulmonary embolism (SPE). Therefore, we used evidence-based medicine to evaluate the effectiveness and safety of CDT in treating SPE. MethodsSearch terms describing CDT in SPE and patients with intermediate pulmonary embolism were entered into the PubMed, Embase and Cochrane Library databases to identify relevant articles without language restrictions published between January 1990 and December 2016. A quality assessment and data extraction were performed by two investigators. The clinical efficacy of and major complications associated with treatment were analysed using a fixed effects model. Key findingsA total of 552 patients in 16 studies were included in this meta-analysis. The clinical success rate in CDT was approximately 100% (95% confidence interval (CI): 99%, 100%), the primary bleeding rate was 0.02% (95% CI: 0%, 0.05%), and mortality during hospitalization was approximately 0% (95% CI: 0%, 0.01%). The mean decrease in pulmonary artery systolic pressure after treatment was −14.9% (95% CI: −19.25%, −10.55%), and the mean post-treatment change in the ratio of the right to the left ventricle (RV/LV) was −0.35% (95% CI: −0.48%, −0.22%). SignificanceCDT is effective and safe as a treatment for SPE and could be a first-line treatment for SPE under specific conditions.

VESS06. Clinical Outcome of Ultrasound-Accelerated Catheter-Directed Thrombolytic Therapy for the Treatment of Submassive Pulmonary Embolism

VESS06. Clinical Outcome of Ultrasound-Accelerated Catheter-Directed Thrombolytic Therapy for the Treatment of Submassive Pulmonary Embolism

BET 1: A glass half full? Thrombolysis for the treatment of submassive pulmonary embolism

A short-cut review was carried out to establish whether thrombolysis in addition to therapeutic anticoagulation could be of benefit in submassive (intermediate risk) pulmonary embolism (PE). 64 directly relevant papers...

Pulmonary Embolism: The Astute Interventional Radiology Clinician.

There has been a resurgence of interest in defining the optimal treatment for severe pulmonary embolism (PE), fueled by pivotal and provocative trials, new catheter-based medical devices, and growing evidence of deleterious short- and long-term outcomes. In this environment, and especially given the multidisciplinary nature of PE care, the interventional radiologist (IR) needs to become an astute, disease-specific expert. This review article describes the following "steps" an IR can take to reach this level: (1) understand PE stratification and epidemiology; (2) recognize the treatment goals for massive PE; (3) recognize the wide range of attitudes toward therapeutic escalation for submassive PE; (4) recognize what we do not know about the treatment of submassive PE and the limitations of current studies; (5) know the literature surrounding inferior vena cava filter insertion for severe PE; (6) integrate into the longitudinal care of the patient; and (7) be at the leading edge of new trials and technologies.

Treatment of Submassive Pulmonary Embolism: Knowing When to be Aggressive and When to be Conservative.

A patient who presents with pulmonary embolism (PE) but without hypotension should undergo risk stratification with echocardiography, computed tomography, and serum biomarker assessment. Submassive PE is identified by the findings of right ventricular dysfunction by physical examination or imaging, or by elevations in serum troponin or brain-type natriuretic peptide in the context of acute PE. Evidence of cardiac strain should prompt evaluation by a multidisciplinary team with experience in the management of submassive PE. Consideration of therapies beyond systemic anticoagulation, such as systemic intravenous thrombolysis, catheter-directed thrombolysis, and percutaneous or surgical embolectomy, must be based on the clinical presentation, the risk of adverse outcome, the skill of the operator, and the bleeding risk. Here, we address the current understanding of submassive PE, new insights into how established therapies alter the natural history of the disease process, and recent advances in treatment options.

5:18 PM, Abstract No. 158 - Safety and efficacy of ultrasound-accelerated thrombolysis for the treatment of submassive pulmonary embolism

Standards for Endovascular Treatment of Pulmonary Embolism. Results: CDT was technically successful in 100% (n1⁄445) of patients. Main pulmonary artery pressure significantly decreased from 49.8 mm to 31.1 mm (po0.0001). Right ventricle dysfunction significantly improved with mean RV/ LV ratios decreasing from 1.59 to 0.93 (po0.0001). There were 6 complications: 4 minor bleeding episodes at access sites, and 2 major bleeding complications (flank and arm hematoma). All cause mortality at 30 days was 0%. There were no re-admissions for PE at 30 days after discharge in all patients. Conclusion: CDT is a safe and efficacious method in the treatment of SPE to reduce acute pulmonary hypertension and RVD. Using a standardized protocol for pulmonary thrombolysis may allow for more widespread adoption of interventional therapy.

Abstract 567: A Successful Use of Tissue Plasminogen Activator and Argatroban for Acute Therapy of a Submassive Pulmonary Embolism Caused by Heparin-Induced Thrombocytopenia

The field of anticoagulation has become a highly relevant and expanding division of medicine. Clinicians must maintain an adequate knowledge of the indications, risks, and benefits of each particular anticoagulant before utilizing them in patient care. Despite great advancements in anticoagulate therapies, areas of uncertainty exist when applying combined use of anticoagulants. This vignette illustrates a unique circumstance of initial therapy combining argatroban with tissue plasminogen activator (tPA) and subsequent transition to warfarin in the management of submassive pulmonary embolism (PE) caused by heparin-induced thrombocytopenia (HIT). There are currently no other published cases or guidelines that have demonstrated this treatment strategy. We present the case of a 56-year-old African American female who was started on argatroban therapy for submassive bilateral PE secondary to HIT. She required tPA after becoming progressively unstable. The argatroban drip was continued without any hemorrhagic complications. This combination of therapy led to her stabilization, and she was ultimately safely transitioned to warfarin therapy for long term maintenance anticoagulation. Argatroban is effective in the prevention and treatment of life-threatening complications of HIT. Very little research has been conducted in patients receiving tPA followed by anticoagulation therapy. This case highlights the successful therapy with combined use of tPA and argatroban followed by warfarin transition in the treatment of submassive PE caused by HIT. We find that tPA was safe and effective when the initial argatroban failed to stabilize our patient. The continued use of argatroban infusion after tPA did not cause any hemorrhagic complications. Furthermore, the overlap use of warfarin with argatroban until an INR greater than 4 was achieved for maintenance therapy did not contribute to any hemorrhagic complications. We conclude that the combination of tPA and argatroban is effective in the acute management of hemodynamically unstable PE caused by HIT without significant hemorrhagic complications.

Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double‐blind, placebo‐controlled randomized trial

Acute pulmonary embolism (PE) can worsen quality of life due to persistent dyspnea or exercise intolerance. Test if tenecteplase increases the probability of a favorable composite patient-oriented outcome after submassive PE. Normotensive patients with PE and right ventricular (RV) strain (by echocardiography or biomarkers) were enrolled from eight hospitals. All patients received low-molecular-weight heparin followed by random assignment to either a single weight-based bolus of tenecteplase or placebo, administered in a double-blinded fashion. The primary composite outcome included: (i) death, circulatory shock, intubation or major bleeding within 5days or (ii) recurrent PE, poor functional capacity (RV dysfunction with either dyspnea at rest or exercise intolerance) or an SF36(®) Physical Component Summary (PCS) score <30 at 90-day follow-up. Eighty-three patients were randomized; 40 to tenecteplase and 43 to placebo. The trial was terminated prematurely. Within 5days, adverse outcomes occurred in three placebo-treated patients (death in one and intubation in two) and one tenecteplase-treated patient (fatal intracranial hemorrhage). At 90days, adverse outcomes occurred in 13 unique placebo-treated patients and five unique tenecteplase-treated patients Thus, 16 (37%) placebo-treated and six (15%) tenecteplase-treated patients had at least one adverse outcome (exact two-sided P=0.017). Treatment of patients with submassive pulmonary embolism with tenecteplase was associated with increased probability of a favorable composite outcome.