A new Trasylol study is shedding more light on possible reasons behind the drug’s higher-than normal death rate.  According to British researchers, while use of the clotting drug aprotinin—known as Trasylol—appears safe during on-pump cardiac surgeries, it appears that combining it with angiotensin-converting enzyme inhibitors—or ACE inhibitors—during off-pump cardiac surgeries shows a significant risk of post-operative kidney dysfunction.  Researchers analyzed 9,875 cardiac surgery patients, most of who (5,434) had on-pump cardiac surgery, meaning their hearts were stopped and they were hooked up to a heart-bypass machine during surgery.  The other patients had off-pump cardiac surgery, in which surgeons operated on their beating hearts.

Trasylol is used to reduce perioperative blood loss and the need for blood transfusion in those patients undergoing cardiopulmonary bypass during coronary artery bypass graft surgery and who are at an increased risk for blood loss and blood transfusion.  ACE inhibitors are used in the treatment of hypertension and congestive heart failure.

The study was prompted by previous research that noted an association between use of aprotinin and renal failure.  Drug maker Bayer voluntarily suspended worldwide marketing of aprotinin after preliminary findings from a Canadian study (BART) suggested the drug increased the risk of death.  That study was a planned analysis and revealed reduced bleeding, but also a mortality increase that nearly reached conventional statistical significance for patients receiving Trasylol.  That trial was halted in October 2007.

Among those who underwent on-pump surgery, there was no significant association between Trasylol and post-operative renal dysfunction, regardless of ACE inhibitor use; however, Trasylol was associated with a more than two-fold increased risk of renal dysfunction among the 848 patients who had off-pump cardiac surgery and who received both Trasylol and ACE inhibitors.  “We recommend that it might be beneficial for patients to discontinue any use of an ACE inhibitor before elective off-pump surgery, particularly patients with a history of renal impairment,” wrote Dr. Ronelle Moulton and Kai Zacharowski, from the department of anesthesia, Bristol Royal Infirmary, United Bristol Healthcare Trust.  Moulton and Zacharowski’s study was published in this week’s issue of The Lancet.  A complete analysis of the BART findings will not be known for some time, Dr. Derek Hausenloy, of The Hatter Cardiovascular Institute, University College London Hospital and Medical School, and colleagues wrote in an accompanying comment.
“While waiting for that analysis, the use of Trasylol in the U.S. and in some European countries has been necessarily restricted, with the consequence that some high-risk patients having cardiac surgery might not receive optimum therapy,” Hausenloy and colleagues noted.

Bayer suspended global Trasylol marketing following consultation with the German Federal Institute for Drugs and Medical Devices (BfArM), the U.S. Food and Drug Administration (FDA), Health Canada, and other health authorities and until final results from the Canadian BART trial can be compiled, received, and evaluated.  The BART study is an independent randomized, controlled trial being conducted in high-risk cardiac surgery patients.  FDA, Health Canada, and other health authorities have indicated a desire to work with Bayer on a program in which physicians might receive Trasylol for treatment of certain surgical patients with medical need during the suspension period.

This entry was posted on Tuesday, February 12th, 2008 at 10:12 am and is filed under Legal News, Pharmaceuticals.