Thrombolysis in Pulmonary Embolism: A Debatable Indication

2001 ◽  
Vol 86 (07) ◽  
pp. 444-451 ◽  
Author(s):  
Samuel Goldhaber
Keyword(s):  
Pulmonary Embolism ◽  
Clinical Trials ◽  
Right Heart Failure ◽  
Funding Agency ◽  
Recurrent Venous Thromboembolism ◽  
Chronic Pulmonary Hypertension ◽  
Coronary Syndromes ◽  
Clot Burden ◽  
Pulmonary Arterial ◽  
Reduction Of Mortality

SummarySuccessfully utilized contemporary pulmonary embolism thrombolysis reverses right heart failure rapidly and safely. This therapeutic approach may lower mortality from pulmonary embolism and reduce morbidity from chronic pulmonary hypertension. Pulmonary embolism thrombolysis remains a debatable indication because large clinical trials using survival as an endpoint have not been carried out. Instead, thrombolysis trials have been undertaken with surrogate endpoints such as reduction in clot burden, reduction in pulmonary arterial pressure, and improvement in right ventricular function. In an era where hundreds of thousands of myocardial infarction patients have participated in thrombolysis trials that focus on survival as the principal endpoint, the much smaller trials of PE thrombolysis have not been sufficiently definitive to achieve a consensus. Pharmaceutical companies have not considered this area of investigation to be a good return on investment, because PE is a much less common problem than acute coronary syndromes. No government funding agency has targeted PE thrombolysis as a priority for clinical research.Currently, the only contemporary thrombolytic regimen for pulmonary embolism that is approved by the Food and Drug Administration is tissue plasminogen activator, in a dose of 100 mg/2 h. New thrombolytic agents under development for pulmonary embolism include reteplase, saruplase, and recombinant staphylokinase. Future clinical trials will require multicenter collaboration and focus on clinically relevant endpoints such as reduction of mortality and recurrent venous thromboembolism.

Clinical Drug Development for the Treatment of Pulmonary Arterial Hypertension: Collaboration With the Pharmaceutical Industry and Regulatory Agencies

2010 ◽  
Vol 9 (4) ◽  
pp. 214-219
Author(s):  
Robyn J. Barst
Keyword(s):  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Drug Development ◽  
Phase 1 ◽  
Preclinical Studies ◽  
Phase 2 ◽  
Phase 3 ◽  
Preclinical Testing ◽  
New Drug ◽  
Pulmonary Arterial

Drug development is the entire process of introducing a new drug to the market. It involves drug discovery, screening, preclinical testing, an Investigational New Drug (IND) application in the US or a Clinical Trial Application (CTA) in the EU, phase 1–3 clinical trials, a New Drug Application (NDA), Food and Drug Administration (FDA) review and approval, and postapproval studies required for continuing safety evaluation. Preclinical testing assesses safety and biologic activity, phase 1 determines safety and dosage, phase 2 evaluates efficacy and side effects, and phase 3 confirms efficacy and monitors adverse effects in a larger number of patients. Postapproval studies provide additional postmarketing data. On average, it takes 15 years from preclinical studies to regulatory approval by the FDA: about 3.5–6.5 years for preclinical, 1–1.5 years for phase 1, 2 years for phase 2, 3–3.5 years for phase 3, and 1.5–2.5 years for filing the NDA and completing the FDA review process. Of approximately 5000 compounds evaluated in preclinical studies, about 5 compounds enter clinical trials, and 1 compound is approved (Tufts Center for the Study of Drug Development, 2011). Most drug development programs include approximately 35–40 phase 1 studies, 15 phase 2 studies, and 3–5 pivotal trials with more than 5000 patients enrolled. Thus, to produce safe and effective drugs in a regulated environment is a highly complex process. Against this backdrop, what is the best way to develop drugs for pulmonary arterial hypertension (PAH), an orphan disease often rapidly fatal within several years of diagnosis and in which spontaneous regression does not occur?

scholarly journals Study of the effect of Occlutech Atrial Flow Regulator on symptoms, hemodynamics, and echocardiographic parameters in advanced pulmonary arterial hypertension

2021 ◽  
Vol 11 (1) ◽  
pp. 204589402198996
Author(s):  
Kothandam Sivakumar ◽  
Gopalavilasam R. Rohitraj ◽  
Monica Rajendran ◽  
Nithya Thivianathan
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
High Risk ◽  
Arterial Hypertension ◽  
Right Heart Failure ◽  
Right Atrial ◽  
Echocardiographic Parameters ◽  
Procedural Complications ◽  
Pulmonary Arterial ◽  
Flow Regulator ◽  
Risk Predictors

Optimal sized balloon atrial septostomy improves hemodynamics in advanced pulmonary arterial hypertension. Occlutech Atrial Flow Regulator is designed to provide an atrial septal fenestration diameter titrated according to the age and right atrial pressures. This observational study analyzed symptoms, exercise distance, oxygen saturations, hemodynamics and echocardiographic parameters after Atrial Flow Regulator implantation in patients with syncope or right-heart failure. Patients with high-risk predictors of mortality during septostomy were scrutinized. Thirty-nine patients (9 children) with syncope (34/39) or right-heart failure (27/39) underwent Atrial Flow Regulator implantation without procedural complications. Six-minute walk distance increased from 310 ± 158.2 to 376.4 ± 182.6 m, none developed syncope. Oxygen saturations reduced from 96.4 ± 6.4% to 92 ± 4.9% at rest and further to 80.3 ± 5.9% on exercise. Right atrial pressures reduced from 9.4 ± 5 (2–27) mmHg to 6.9 ± 2.6 (1–12) mmHg, while cardiac index increased from 2.4 ± 0.8 (0.98–4.3) to 3 ± 1 (1.1–5.3) L/min/m2 and systemic oxygen transport increased from 546.1 ± 157.9 (256.2–910.5) to 637.2 ± 191.1 (301.3–1020.2) ml/min. Echocardiographic improvement included significant reduction of pericardial effusion and inferior caval congestion at a median follow-up of 37 months. Overall survival improved except two early and one late deaths in high-risk patients. Five of seven patients with advanced disease and key hemodynamic predictors of mortality survived. Acute hemodynamic benefits in pulmonary arterial hypertension after Atrial Flow Regulator were improved cardiac output, systemic oxygen transport, and reduced right atrial pressures. Improvement of symptoms especially syncope, exercise duration, and right ventricular systolic function as well as device patency were sustained on mid-term follow-up. Implantation was safe in all including young children without procedural complications. Mortality was noted only in patients who had high-risk predictors and patients at advanced stage of the disease.

A Massive Pulmonary Embolism Treatment Protocol: How Trauma Performance Improvement Affects Outcome Throughout the Hospital System

2010 ◽  
Vol 76 (2) ◽  
pp. 145-148
Author(s):  
Catherine Garrison Velopulos ◽  
Mark Zumberg ◽  
Priscilla Mcauliffe ◽  
Lawrence Lottenberg ◽  
A. Joseph Layon
Keyword(s):  
Pulmonary Embolism ◽  
Sudden Death ◽  
Performance Improvement ◽  
Pulmonary Embolus ◽  
Treatment Protocol ◽  
Right Heart Failure ◽  
Hospital Performance ◽  
Massive Pulmonary Embolism ◽  
Hospital System ◽  
Submassive Pulmonary Embolism

Trauma performance improvement is the hallmark of a mature trauma center. If loop closure is to be complete, preventable deaths must result in significant change in management and the establishment of protocol-driven improvements so such an instance does not recur. The trauma performance improvement committee reviewed a case of a massive pulmonary embolus and determined that this was a preventable death. The hospital performance improvement committee then initiated a root cause analysis, which led to creation of a treatment protocol for patients with massive or submassive pulmonary embolism. A focused review of the first 6 months of the implementation of the protocol was undertaken. Four patients over a 6-month period had massive or submassive pulmonary embolus. All four had sudden death or near sudden death and were appropriately resuscitated. All four sustained right heart failure. Two patients were treated by catheter-directed fibrinolysis, one with catheter-directed suction embolectomy, and one by surgical pulmonary embolectomy. All survived with full neurologic function. Trauma performance improvement is the model by which all hospital performance improvement should be done. Preventable deaths can result in change, which can have a future impact on survival in potentially lethal scenarios.

scholarly journals Pulmonary Vessel Obstruction Does Not Correlate with Severity of Pulmonary Embolism

2019 ◽  
Vol 8 (5) ◽  
pp. 584 ◽  
Author(s):  
Marianne Lerche ◽  
Nikolaos Bailis ◽  
Mideia Akritidou ◽  
Hans Jonas Meyer ◽  
Alexey Surov
Keyword(s):  
Pulmonary Embolism ◽  
Statistical Significance ◽  
Pulmonary Arteries ◽  
Severity Index ◽  
Clinical Severity ◽  
Pulmonary Vessel ◽  
Wells Score ◽  
Clot Burden ◽  
Spearman’S Correlation ◽  
D Dimer

The aim of the present study was to analyze possible relationships between pulmonary vessel obstruction and clinically relevant parameters and scores in patients with pulmonary embolism (PE). Overall, 246 patients (48.8% women and 51.2% men) with a mean age of 64.0 ± 17.1 years were involved in the retrospective study. The following clinical scores were calculated in the patients: Wells score, Geneva score, and pulmonary embolism severity index (PESI) score. Levels of D-dimer (µg/mL), lactate, pH, troponin, and N-terminal natriuretic peptide (BNP, pg/mL) were acquired. Thrombotic obstruction of the pulmonary arteries was quantified according to Mastora score. The data collected were evaluated by means of descriptive statistics. Spearman’s correlation coefficient was used to analyze associations between the investigated parameters. P values < 0.05 were taken to indicate statistical significance. Mastora score correlated weakly with lactate level and tended to correlate with D-dimer and BNP levels. No other clinical or serological parameters correlated significantly with clot burden. Thrombotic obstruction of pulmonary vessels did not correlate with clinical severity of PE.

scholarly journals Recent advances in the management of pulmonary arterial hypertension

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2755 ◽  
Author(s):  
Halley Tsai ◽  
Yon K. Sung ◽  
Vinicio de Jesus Perez
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
Soluble Guanylate Cyclase ◽  
Right Heart Failure ◽  
New Drugs ◽  
Triple Combination Therapy ◽  
Treatment Naïve ◽  
Treatment Paradigm ◽  
Pulmonary Arterial

Over the past 20 years, there has been an explosion in the development of therapeutics to treat pulmonary arterial hypertension (PAH), a rare but life-threatening disorder associated with progressive elevation of pulmonary pressures and severe right heart failure. Recently, the field has seen the introduction of riociguat, a soluble guanylate cyclase stimulator, a new endothelin receptor antagonist (macitentan), and oral prostanoids (treprostinil and selexipag). Besides new drugs, there have been significant advances in defining the role of upfront combination therapy in treatment-naïve patients as well as proposed methods to deliver systemic prostanoids by use of implantable pumps. In this review, we will touch upon the most important developments in PAH therapeutics over the last three years and how these have changed the guidelines for the treatment of PAH. These exciting developments herald a new era in the treatment of PAH which will be punctuated by the use of more clinically relevant endpoints in clinical research trials and a novel treatment paradigm that may involve upfront double- or triple-combination therapy. We anticipate that the future will make use of these strategies to test the efficacy of upcoming new drugs that aspire to reduce disease progression and improve survival in patients afflicted with this devastating disease.

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