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Semin Thromb Hemost
DOI: 10.1055/s-0044-1781451
Review Article

Fibrinolytic Agents in Thromboembolic Diseases: Historical Perspectives and Approved Indications

Sina Rashedi
1   Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
,
Christie M. Greason
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Parham Sadeghipour
1   Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
3   Clinical Trial Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran
,
Azita H. Talasaz
4   Department of Pharmacotherapy and Outcomes Sciences, Virginia Commonwealth University, Richmond, Virginia
5   Department of Pharmacy Practice, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, New York, New York
6   Department of Pharmacy, New York-Presbyterian Hospital Columbia University Medical Center, New York, New York
,
Michelle L. O'Donoghue
7   Division of Cardiovascular Medicine, TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
David Jimenez
8   Respiratory Department, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain
9   Medicine Department, Universidad de Alcalá (IRYCIS), Madrid, Spain
10   CIBER Enfermedades Respiratorias (CIBERES), Madrid, Spain
,
Manuel Monreal
11   Department of Internal Medicine, Hospital Germans Trias i Pujol, Badalona, Spain
12   Universidad Catolica de Murcia, Murcia, Spain
,
Christopher D. Anderson
13   Program in Medical and Population Genetics, Broad Institute of Harvard and the Massachusetts Institute of Technology, Boston, Massachusetts
14   McCance Center for Brain Health, Massachusetts General Hospital, Boston, Massachusetts
15   Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts
,
Mitchell S. V. Elkind
16   Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York
17   Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York
,
Lisa M. Baumann Kreuziger
18   Medical College of Wisconsin, Milwaukee, Wisconsin
19   Blood Research Institute, Versiti, Milwaukee, Wisconsin
,
Irene M. Lang
20   Department of Internal Medicine II, Cardiology and Center of Cardiovascular Medicine, Medical University of Vienna, Vienna, Austria
,
Samuel Z. Goldhaber
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
21   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Stavros V. Konstantinides
22   Center for Thrombosis and Haemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
23   Department of Cardiology, Democritus University of Thrace, Alexandroupolis, Greece
,
Gregory Piazza
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
21   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Harlan M. Krumholz
24   YNHH/Yale Center for Outcomes Research and Evaluation (CORE), New Haven, Connecticut
25   Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut
26   Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut
,
Eugene Braunwald
7   Division of Cardiovascular Medicine, TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
21   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Behnood Bikdeli
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
21   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
24   YNHH/Yale Center for Outcomes Research and Evaluation (CORE), New Haven, Connecticut
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Abstract

Fibrinolytic agents catalyze the conversion of the inactive proenzyme plasminogen into the active protease plasmin, degrading fibrin within the thrombus and recanalizing occluded vessels. The history of these medications dates to the discovery of the first fibrinolytic compound, streptokinase, from bacterial cultures in 1933. Over time, researchers identified two other plasminogen activators in human samples, namely urokinase and tissue plasminogen activator (tPA). Subsequently, tPA was cloned using recombinant DNA methods to produce alteplase. Several additional derivatives of tPA, such as tenecteplase and reteplase, were developed to extend the plasma half-life of tPA. Over the past decades, fibrinolytic medications have been widely used to manage patients with venous and arterial thromboembolic events. Currently, alteplase is approved by the U.S. Food and Drug Administration (FDA) for use in patients with pulmonary embolism with hemodynamic compromise, ST-segment elevation myocardial infarction (STEMI), acute ischemic stroke, and central venous access device occlusion. Reteplase and tenecteplase have also received FDA approval for treating patients with STEMI. This review provides an overview of the historical background related to fibrinolytic agents and briefly summarizes their approved indications across various thromboembolic diseases.

Keywords

fibrinolytic agents - plasminogen activator - thromboembolism

Disclosures

Dr. O'Donoghue has received grant funding from Amgen, Novartis, and AstraZeneca and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. O'Donoghue has advisory roles at AstraZeneca, Janssen, and NovoNordisk. Dr. Jimenez is a member of the Steering Committee of the PEITHO III. Dr. Monreal reports nonrestricted research grants to sponsor the RIETE registry from Sanofi and Rovi Laboratories. Dr. Anderson is supported by NIH R01NS103924, U01NS069673, AHA 18SFRN34250007, AHA-Bugher 21SFRN812095, and the MGH McCance Center for Brain Health. Dr. Anderson has received sponsored research support from Bayer AG, Massachusetts General Hospital, and the American Heart Association and has consulted for ApoPharma Inc. Dr. Elkind is an employee of the American Heart Association and has received study drug-in-kind from the BMS-Pfizer Alliance for Eliquis and ancillary funding from Roche for an NIH-funded trial of stroke prevention; honoraria from the Atria Academy of Science and Medicine; and royalties for chapters on stroke from UpToDate. Dr. Baumann Kreuziger has received sponsored research support from NHLBI, the American Society of Hematology, Takeda, and CSL Behring. Dr. Lang receives research support from AOP-Health, and consulting fees from AOP-Health, J&J, MSD, and United Therapeutics. Dr. Lang receives lecture fees from AOP-Health, J&J, MSD, Pulnovo, and United Therapeutics, and support for attending meetings from Medtronic. Dr. Konstantinides reports personal lecture and advisory fees as well as research grants via his institution from Bayer AG, Boston Scientific, Daiichi-Sankyo, LumiraDx, and Penumbra; he also reports personal lecture/advisory fees from MSD and Pfizer—Bristol-Myers Squibb. Dr. Piazza has received research grants from BMS/Pfizer, Janssen, Alexion, Bayer, Amgen, BSC, Esperion, and 1R01HL164717–01. Dr. Piazza has advisory roles at BSC, Amgen, BCRI, PERC, NAMSA, BMS, Janssen, and Regeneron. Dr. Krumholz received expenses and/or personal fees from United-Health, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, and F-Prime; he is a co-founder of Refactor Health and Hugo-Health; and contracts through Yale New Haven Hospital from the Centers for Medicare & Medicaid Services and through Yale University from Johnson & Johnson. Dr. Braunwald reports research grants through his institution from Astra Zeneca, Daiichi Sankyo, and Novartis, and consultancy fees from Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Cardurion, Edgewise, and Verve. Dr. Bikdeli is supported by a Career Development Award from the American Heart Association and VIVA Physicians (#938814). Dr. Bikdeli was supported by the Scott Schoen and Nancy Adams IGNITE Award and is supported by the Mary Ann Tynan Research Scientist award from the Mary Horrigan Connors Center for Women's Health and Gender Biology at Brigham and Women's Hospital, and the Heart and Vascular Center Junior Faculty Award from Brigham and Women's Hospital. Dr. Bikdeli reports that he was a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of IVC filters. Dr. Bikdeli has not been involved in the litigation in 2022–2024 nor has he received any compensation in 2022–2024. Dr. Bikdeli reports that he is a member of the Medical Advisory Board for the North American Thrombosis Forum, and serves in the Data Safety and Monitory Board of the NAIL-IT trial funded by the National Heart, Lung, and Blood Institute, and Translational Sciences. Other authors report no disclosures.




Publication History

Article published online:
01 March 2024

© 2024. Thieme. All rights reserved.

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