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2007-9-3 13:36:01 |
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Those who underwent cardiac surgery and took aprotinin, an anti-bleeding drug were at a significantly higher risk of death compared to those who received the surgery, but did not take any hemorrhage-sparing medication, according to a new study scheduled to appear in the Feb 7 2007 issue of the Journal of the American Medical Association. The results of the study show taking aprotinin could pose a higher risk of death to the patients who received coronary artery bypass graft (CABG) surgery even compared to other two medications namely aminocaproic acid and tranexamic acid, which were used for the same antibleeding effect. The observational study was a follow-up of one study published last year by the same researchers with Dr. Dennis Mangano lead investigator, who represents The Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation. The earlier study has already linked the anti-bleeding agent aprotinin with an elevated risk of kidney and heart failure as well as stroke. According to the researchers, "acute safety concerns have been raised recently regarding certain hemorrhage-sparing medications commonly used in cardiac surgery. However no comprehensive data exist regarding their associations with long-term mortality". Thus, the purpose of this current study was to "contrast long term all-cause mortality in patients undergoing CABG surgery according to use of 2 lysine analog antifibrinolytics (aminocaproic acid and tranexamic acid), the serine protease inhibitor aprotinin, or no antibleeding agent.Ħħ The study involved a total of 3,876 of patients from 62 cardiac centers from multiple countries who received CABG surgery. The researchers reviewed the long term survival data from the patients annually for five years. The patients were divided into four groups based on the antibleeding medications they took including aminocaproic acid, tranexamic acid, aprotinin and no antibleeding agent. Then they used statistical methods, covariate analysis and multivariable analysis to compare the mortality rates associated with the medications they took. The researchers found that the death rate for those who took aprotinin was significantly higher, 20.8 percent over 5 years. This is compared to 15.8 percent for those on aminocaproic acid and 14.7 percent for those on tranexamic acid. Without taking any antibleeding agent, the mortality rate was 12.7 percent over the five years. Compared to those taking no hemorrhage-sparing medication, taking aprotinin seemingly raised the death risk by 48 percent whereas taking aminocaproic acid or tranexamic acid did not raise the risk significantly, 3 percent versus 7 percent. Results from a multivariable logistic regression model indicated that taking aprotinin was strongly predictive of death over the five years whereas taking either of other two medications was not. Based on what they found, the researchers concluded in their report that "use of aprotinin among patients undergoing CABG surgery does not appear prudent because safer and less expensive alternatives (i.e. aminocaproic acid and tranexamic acid) are available.Ħħ Bayer Pharmaceuticals, the maker of aprotinin, today issued a statement saying that the company has conducted a preliminary review of the findings and it believes that the methodological and analytical approaches used in the study were similar to the ones used in the authors' early study and they are not reliable and do not support their reported conclusions. The statement suggests that those who were treated with aprotinin were generally considered sicker and at greater risk for mortality, meaning that the seemingly elevated death risk may be associated with their conditions rather than the medication they took. Additionally, Bayer says that there are differences in clinical practices among the cardiac centers considered in the study, which may affect the reported findings. Aprotinin, marketed under the name Trasylol, was first approved by the Food and Drug Administration for patients undergoing CABG using cardiopulmonary bypass to prevent bleeding. The drug inhibits certain enzymes that increase the risk for bleeding. The early study by Dr. Mangano and team, published on Jan 26 2006 in The New England Journal of Medicine showed that the occurrence of serious kidney damage, heart attack or myocardial infarction and stroke were more common among CABG patients receiving aprotinin than those receiving no medications intended to decrease blood loss or taking other antibleeding agents. These serious side-effects may be associated with the clot formation promoted by aprotinin. Another early study, according to the FDA, showed that use of aprotinin in CABG patients resulted in a higher risk of clot formation or bypass closure within coronary artery bypass grafts, compared to those who received a placebo. The FDA sees a limitation in the early study by Dr. Mangano though. That is, patients in the study were not randomly assigned treatments, which caused biases. In spite of the early findings, the federal agency did not pull aprotinin out of the market because it said the study findings are not in agreement with the results submitted by the drug manufacturer in the application for marketing aprotinin. Instead, the FDA issued a statement on Sept 29, 2006 to alert physicians to monitor those who were on aprotinin and ask them to consider prescribing aprotinin only if its benefits outweigh its risks. Late on Dec. 15, 2006, FDA asked Bayer Pharmaceuticals Corporation, Leverkusen, Germany to change the label for aprotinin to warn physicians and patients of the risks associated with the medication. The FDA has yet to respond to what Dr Mangano and colleagues found regarding the association between aprotinin and elevated risk of mortality in CABG patients. For more information about the current study and aprotinin, visit the following sites: http://www.trasylol.com/main.htm http://jama.ama-assn.org/cgi/content/full/297/5/471 http://www.fda.gov/cder/drug/infopage/aprotinin/default.htm Source Mortality Associated With Aprotinin During 5 Years Following Coronary Artery Bypass Graft Surgery Dennis T. Mangano, PhD, MD; Yinghui Miao, MD, MPH; Alain Vuylsteke, MD; Iulia C. Tudor, PhD; Rajiv Juneja, MD; Daniela Filipescu, MD; Andreas Hoeft, MD; Manuel L. Fontes, MD; Zak Hillel, PhD, MD; Elisabeth Ott, MD; Tatiana Titov, MD, PhD; Cynthia Dietzel, MD; Jack Levin, MD; for the Investigators of The Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation |
