Aprotinin, a drug used to limit bleeding, was temporarily suspended from marketing in the U.S. in November 2007 after a small Canadian study was stopped because similar findings were discovered. The drug, Trasylol, is manufactured by Baylor AG.
"We're not surprised by the results,” says Dr. Andrew Shaw, an associate professor in Duke Medicine’s department of anesthesiology and the lead author of the paper which appears in the February 21 edition of the New England Journal of Medicine. “It's what we expected to find.”
The Duke study is significant because “it is more than twice the size of the next largest study of aprotinin,” says Shaw. The prospective data was collected between 1996 and 2005. “Unlike the highly selected nature of randomized trial populations, our data represent the every day cardiac bypass surgery patient population. The data were collected at a time when aprotinin was thought to be safe.”
The Duke team started analyzing its database of patients after a 2006 NEJM study reported aprotinin use may increase the risk of heart attack, stroke and serious kidney injury.
“We were looking for an association between exposure to the drug and subsequent adverse outcomes,” Shaw says. “We found an increased incidence of death in patients who received aprotinin. That higher death rate seemed to persist even when we were able to control for the differences seen between the patient groups.”
Shaw and his Duke colleagues also linked aprotinin to impaired kidney function. “Kidney function is measured by serum creatinine levels which indicate how well the blood is filtering waste products,” he says. The study found aprotinin use increased serum creatinine levels, but they did not report an increase in patients needing dialysis. Shaw believes “that’s because we probably didn’t have enough patients who needed dialysis in our study to detect a significant statistical difference, although the incidence was numerically higher.”
Of the 10,275 patients studied, 1343 patients (13.2%) received aprotinin, 6776 patients (66.8%) received aminocaproic acid (another drug used to limit bleeding) and 2029 patients (20.0%) received no therapy. All patients underwent coronary-artery bypass surgery (CABG), and 1181 of them also underwent valve surgery. Patients who received either aminocaproic acid or no therapy did not have high rates of death or poor kidney function seen in the aprotinin group.
After gaining FDA approval in 1993, aprotinin was used routinely during cardiac surgery, particularly on high-risk patients, to reduce bleeding and the need for blood transfusion. According to previously published research, patients undergoing cardiac surgery receive approximately one fifth of all the red cell transfusions in the U.S., and each unit transfused is known to increase the risk of infection.
Shaw says this study does not rule out the possibility that the increased death rate was due to high-risk, sicker patients receiving the drug. “You would expect sicker patients would be more likely to die,” he said.
“The unanswered question is, ‘are there differences between the patient groups that we were unable to detect that led to the increased death rate, or is the death rate due to exposure to the drug?’
“Our study doesn’t answer that question nor was it designed to,” he says. “But it does further raise the question of the safety of aprotinin. And, on a broader scale, it highlights the importance of post-marketing observational studies of drugs that are widely used.”
Lauren Shaftel Williams | EurekAlert!
Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland
Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
23.03.2017 | Life Sciences
23.03.2017 | Power and Electrical Engineering
23.03.2017 | Earth Sciences