As a cardiac anesthesiologist, I have used my share of Aprotinin and swore that it really did reduce bleeding. I was skeptical about the Mangano study but since it’s publication, accumulating data points to the fact that Aprotinin may not be that safe and that the cheaper antifibrinolytics – Aminocaproic acid and Tranexamic acid – may be as effective.

The BART Trial, being carried on in Canada is supposed to provide a good comparison of the three drugs. Below is an early release  on this study: 

Early Communication about an Ongoing Safety Review
Aprotinin Injection (marketed as Trasylol)

This information reflects FDA’s current analysis of available data concerning these drugs. Posting this information does not mean that FDA has concluded there is a causal relationship between the drug products and the emerging safety issue.  Nor does it mean that FDA is advising health care professionals to discontinue prescribing these products. FDA is considering, but has not reached a conclusion about whether this information warrants any regulatory action. FDA intends to update this document when additional information or analyses become available.

On October 19, 2007, FDA was notified of the Data Safety Monitoring Board’s (DSMB) recommendation to stop patient enrollment in the aprotinin (marketed as Trasylol by Bayer, Inc.) treatment group arm of the:  Blood conservation using antifibrinolytics: A randomized trial in a cardiac surgery population (BART) study.  The preliminary findings suggest that, compared to the antifibrinolytic drugs, epsilon-aminocaproic acid and tranexamic acid, aprotinin increases the risk of death. 

The BART study was designed to test the hypothesis that aprotinin was superior to epsilon-aminocaproic acid and tranexamic acid in decreasing the occurrence of massive bleeding associated with cardiac surgery.  The study had planned to enroll approximately 3,000 adult Canadian patients who were to undergo various types of cardiac surgery that placed them at high risk for bleeding. 

Information from the interim analyses performed by the DSMB is limited, but FDA has been informed that:

• the 30- day mortality in the aprotinin group nearly had reached conventional statistical significance at the interim analysis, when compared to either epsilon-aminocaproic acid or tranexamic acid;

• a trend toward increased mortality in the aprotinin group had been observed throughout the study;

• the use of aprotinin was associated with less serious bleeding than either of the comparator drugs; however, more deaths due to hemorrhage had been observed among patients receiving aprotinin;

• the DSMB concluded that continued enrollment of patients into the aprotinin group was unlikely to significantly change the study findings.

Additional data collection and analyses must be performed to more thoroughly assess the findings from the BART study.  However, these preliminary data support the findings from observational studies that also suggested increased risks for mortality when aprotinin was compared to other antifibrinolytic drugs.  These observational studies were discussed at a September 12, 2007, joint meeting of the Cardiovascular and Renal Drugs and Drug Safety and Risk Management Advisory Committees.  

In light of the preliminary BART study findings, FDA anticipates re-evaluation of the overall risks and benefits of Trasylol. This re-evaluation may result in the need to revise the labeling or other regulatory actions.  Until this process has been completed, healthcare providers who are considering use of Trasylol should be aware of the risks and benefits described in the labeling for Trasylol and the accumulating data suggesting Trasylol administration increases the risk for death compared to other antifibrinolytic drugs. 

Trasylol is currently approved for prophylactic use to reduce perioperative blood loss and the need for blood transfusion in patients undergoing cardiopulmonary bypass in the course of coronary artery bypass graft (CABG) surgery who are at an increased risk for blood loss and blood transfusion.

This early communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs.  FDA will work with the sponsor of the BART study and the manufacturer of Trasylol to fully evaluate the risks and benefits associated with the use of Trasylol.  As soon as this process is complete, FDA will communicate the conclusions and recommendations to the public. 

The FDA urges healthcare professionals to promptly report serious and unexpected adverse reactions associated with Trasylol to Bayer or to the FDA MedWatch reporting program, as described below. 

• online at www.fda.gov/medwatch/report.htm
• by returning the postage-paid FDA form 3500 (available in PDF format at www.fda.gov/medwatch/getforms.htm) to 5600 Fishers Lane, Rockville, MD 20852-9787
• faxing the form to 1-800-FDA-0178
• by phone at 1-800-332-1088

Is this the end for Aprotinin?

jnkdg

Below is the left lung of a 55-year-old patient undergoing lung transplantation. The patient had smoked 3-4 packs-a-day for the last 40 years. He had very severe emphysematous  disease and pulmonary hypertension. Appreciate the balloon-nature of the lung.

jnkdg

Our healthcare system is going to see a change – more sooner than later. How that is going to look is going to depend more on what the Legislature looks like.

Let’s make the assumption that we have an Universal Healthcare of sorts. No matter how much money is infused into this system, care must be taken to ensure some form of equity. Which means certain patients are not going to get the care or procedures that a physician deems fit to prolong life. That is just the way things are going to be.  So maybe octagenarians are not going to get the Redo-CABG or double valve or maybe the the patient who came into the ER after a motor vehicle accident with a systolic pressure of 60 and a pH on arterial bloood gas of 6.75 will not be rushed to the operating room. In the above examples, the prognoses do not support the use of the available resources.

My point is, even though people are lamenting the present state of our healthcare system, the alternative may have it’s own impediments to optimal care of the sick. A centralized form of healthcare is going to have a control system. We think the HMOs are bad now. Wait till you have to call Washington DC to approve a procedure!

jnkdg