Friday November 9, 2007
Fall of Aprotinin !
This week Bayer, maker of aprotinin, has announced that it has elected to temporarily suspend worldwide marketing of Trasylol® (aprotinin injection) until final results from the Canadian BART trial is available 3. The BART study is an independent randomized, controlled trial being conducted in high-risk cardiac surgery patients 4. On October 19, 2007, FDA was notified of the Data Safety Monitoring Board’s (DSMB) recommendation to stop patient enrollment in the aprotinin treatment group arm of the BART study. The preliminary findings suggest that, compared to the antifibrinolytic drugs, epsilon-aminocaproic acid and tranexamic acid, aprotinin increases the risk of death 5.
BART = Blood conservation using antifibrinolytics: A randomized trial in a cardiac surgery population
In last couple of years, use of aprotinin has been questioned following coronary artery bypass grafting, particularly in view of availability of safer and less expensive alternatives (aminocaproic acid and tranexamic acid) . Aprotinin, also known as bovine pancreatic trypsin inhibitor is a protein that is administered by injection to reduce bleeding during complex surgery. Its main effect is the slowing down of fibrinolysis .
One major article published in January 2006 in The New England Journal of Medicine concluded that the use of aprotinin was associated with a dose-dependent doubling to tripling in the risk of renal failure requiring dialysis among patients undergoing primary or complex coronary-artery surgery. Also, it was suggested that for the majority of patients undergoing primary surgery, evidence of multiorgan damage involving the heart (myocardial infarction or heart failure) and the brain (encephalopathy) in addition to the kidneys shows a generalized pattern of ischemic injury 1.
Same group of investigators, published an article in February 2007 issue of JAMA, looking into mortality data of 3876 patients from 62 medical centers assessed at 6 weeks, 6 months, and annually for 5 years after CABG surgery 2, comparing aminocaproic acid and tranexamic acid, aprotinin, or no antibleeding agent (control). Study found that Aprotinin treatment was associated with significantly increased long term mortality compared with control, whereas neither aminocaproic acid nor tranexamic acid was associated with increased mortality.
FDA issued a relabeling of aprotinin on December 15, 2006, confining it to use only in high-risk coronary artery bypass graft patients.
References / suggested readings: Click to get article/abstract
1. The Risk Associated with Aprotinin in Cardiac Surgery - NEJM Jan. 26, 2006 Volume 354:353-365
2. Mortality Associated With Aprotinin During 5 Years Following Coronary Artery Bypass Graft Surgery - JAMA. 2007;297:471-479, Vol. 297 No. 5, February 7, 2007
3. Bayer Temporarily Suspends Global Trasylol® Marketing - trasylol.com
4. MAJOR OUTCOMES FOLLOWING HIGH RISK CARDIAC SURGERY Canadian Journal of Anesthesia 53:26231 (2006)
5. FDA Public Health Advisory - fda.gov
