[HSF] Aprotinin
Michael Firstenberg
msfirst at gmail.com
Sun Nov 19 19:20:18 EST 2006
do you have a link?
michael
On Nov 19, 2006, at 7:16 PM, Ben Bidstrup wrote:
> You might find it interesting to read the FDA transcript of the
> Cardiovascular and Renal Advisory Board 21 September.
>
>> Please don't disparage Dennis Mangano too much. He is, or at
>> least was, a
>> very capable clinical cardiac anesthesiologist and is fully
>> cognizant of all
>> of the issues regarding intra-operative bleeding and post-
>> operative care of
>> cardiac surgery patients. That explains Dennis' consistent
>> ability to focus
>> and publish provocatively on real life issues that confronting
>> surgeons and
>> anesthesiologists on a day to day basis. The methodology of his
>> paper in
>> the NEJM is open to question. Dr. Mangano's credentials are not!
>> Fraser Keith
>>
>> -----Original Message-----
>> From: openheart-l-bounces at lists.hsforum.com
>> [mailto:openheart-l-bounces at lists.hsforum.com] On Behalf Of Michael
>> Firstenberg
>> Sent: Sunday, November 19, 2006 10:18 AM
>> To: OpenHeart-L at lists.hsforum.com
>> Subject: Re: [HSF] Aprotinin
>>
>> If I recall Mangino is not a surgeon - in fact is he not an
>> anesthesiologist, as are many of the people who recently write
>> these articles about "bad cardiac drugs"? Has he actually had to
>> stand at the foot of a bed or in the OR for countless hours
>> watching patient bleed to death and deal first hand with the
>> consequences of massive transfusions. Yes, renal failure and
>> dialysis is bad bad bad - but compare that with right heart
>> failure/ARDS/massive pressor requirements/etc from excessive
>> bleeding (and the hypotension and associated ATN/renal failure
>> anyhow). My guess is he is home in bed all nice an cozy with his
>> pager off at the end of his shift.
>>
>> -michael
>>
>>
>>
>>
>> On Nov 19, 2006, at 2:24 AM, Ani Anyanwu wrote:
>>
>>> Prasanna
>>>
>>> Well many would I suspect call it unbridled.
>>>
>>> The following would generally receive aprotinin in my institution
>>> 1) reoperations
>>> 2) operations on the aortic arch or descending aorta
>>> 3) transplant and VAD procedures
>>> 4) operations on patients on clopidogrel
>>> 5) combined valvular and CABG
>>> 6) Patients with renal impairment
>>> 7) Patients where ability to tolerate transfusion or bleeding
>>> complications is thought to be marginal including - most
>>> patients aged 70 or above, patients with severe lung disease,
>>> poor LV function, severe pulmonary hypertension, multiple
>>> comorbidity etc. Certainly almost all octogenrians would get
>>> aprotinin - even for CABG.
>>> 8) Paradoxically, young patients in their 20s or 30s (where
>>> avoidance of blood transfusion should be the goal in all patients)
>>> 9) Multiple valvular procedures (excluding tricuspid valve)
>>> 10) cases with anticipated bypass run more than 3 hours
>>> (including complex mitral repairs)
>>>
>>> As you can see there is not much left - so maybe it is
>>> unbridled! As you implied we obviously would not use it for an
>>> ASD or isolated AVR, but these constitute a small minority of
>>> our procedures. Personally I would use it for practically every
>>> operation - including all CABGs - but that is a personal opinion
>>> as I believe there are non-hematological benefits of the drug
>>> and like you
>> > strongly believe in blood conservation. I do not have any
>> interests
>>> or links to industry.
>>>
>>> Actually Ben brought up something that I had never thought of -
>>> correct me if I am wrong but Aprotinin is the only agent
>>> licensed as a blood conservation agent for heart surgery?
>>>
>>> Ani
>>> ----- Original Message -----
>>> From: psimha<mailto:prasannasimha at gmail.com>
>>> To: OpenHeart-L at lists.hsforum.com<mailto:OpenHeart-
>>> L at lists.hsforum.com>
>>> Sent: Sunday, November 19, 2006 12:00 AM
>>> Subject: Re: [HSF] Aprotinin
>>>
>>>
>>> Ani - are you really using it "unbridled" or liberally ? Do
>>> you use it
>>> for an ASD or for a straight forward valve replacement ? or
>>> any other
>>> case with a short bypass run ?
>>> I did not say I will not use it in a redo - in fact if you
>>> note my
>>> original post I said I did use it in redo's ?
>>> And Yes , I believe very strongly in blood conservation and
>>> believe that
>>> Aprotinin is one (and not the only ) cog in the wheel.
>> > Prasanna
>>>
>>> Ani Anyanwu wrote:
>>>> Prasanna
>>>>
>>>> We use aprotinin in an unbridled way and are certainly yet to
>>>> see this price.
>>>> - we have no more an incidence of renal failure than other
>>>> institutions have (this we know because incidence of dialysis
>>>> postop in all New York Hospitals is tracked by the State
>>>> Department of Health)
>>>> - we have no suggestion of an increase in early vein graft
>>>> thrombosis (this should transform into higher periop MI and
>>>> mortality, our CABG mortality rate has remained around 1.5% last
>>>> 3 years)
>>>> - we have not experienced any adverse events that caused us to
>>>> be concerned about its use, except fatal thrombosis in 2
>>>> patients with Factor V Lieden deficiency having circulatory
>>>> arrest so we now routinely screen for this defect in all
>>>> circulatory arrest cases.
>>>>
>>>> The price we are paying is a low incidence of transfusion of
>>>> blood products and a low re-exploration rate (<2% last 2 years
>>>> even with 18% being redos and almost 20% aortic cases). Maybe
>>>> there are other unknown adverse effects which will catch up
>>>> with us, but for know they are unknown (and we wont be
>>>> responsible; remember it is the drug companies not doctors
>>>> being sued for COX2 inhibitors).
>>>>
>>>> Maybe when Mangano is bored he might do another study, and
>>>> then what will you do? For those who use Amicar, how do we
>>>> really know it is any safer - the drug is not even licensed for
>>>> human use in many European countries. Perhaps even his next
>>>> study will be on morbidity of plasma and platelet
>>>> transfusions....then what will we do?
>>>>
>>>> Ani
>>>> ----- Original Message -----
>>>> From:
>>>> prasannasimha<mailto:prasannasimha at gmail.com<mailto:prasannasimha at g
>>>> ma
>>>> il.com>>
>>>> To: OpenHeart-L at lists.hsforum.com<mailto:OpenHeart-
>>>> L at lists.hsforum.com<mailto:OpenHeart-
>>>> L at lists.hsforum.com<mailto:OpenHeart-L at lists.hsforum.com>>
>>>> Sent: Saturday, November 18, 2006 9:37 PM
>>>> Subject: Re: [HSF] Aprotinin
>>>>
>>>>
>>>> The thing I want to say is that be it Vioxx / Aprotinin/blood/
>>>> Oxygen -
>>>> they are all drugs and have effects and side effects. The
>>>> present mess
>>>> that the pharmacological companies are in is just because of
>>>> their
>>>> unbridled enthusiasm (or greed) to ,make a quick buck and it
>>>> backfires
>>>> on them. COX2 Inhibitors have a specific role unfortunately
>>>> I even saw
>>>> my dentist prescribing it for tooth pain !! Who marketed it
>>>> to him as a
>>>> good NSAID ? I told him about the literature and my
>>>> concerns (this was
>>>> prior to Vioxx) . They were trying to market Valdecoxib for
>>>> post cardiac
>>>> surgery pain !!_ and I told them you should not be doing that
>>>> - but did
>>>> they listen ? and bang in a few months a controversy breaks
>>>> out. The
>>>> wife of colleague of mine was taking valdecoxib sample (she
>>>> is a Doctor
>>>> too) as the sample was around and the premenopausal lady
>>>> ended up with a
>>>> coronary thrombosis !!
>>>> Every drug has a role and an indication based on good
>>>> clinical judgment
>> >> - unfortunately we pay the price when its use is unbridled.
>>>> Prasanna
>>>>
>>>> hgrmd at aol.com<mailto:hgrmd at aol.com<mailto:hgrmd at aol.com<mailto:hgrm
>>>> d@
>>>> aol.com>> wrote:
>>>>> Prasanna and Ajit,
>>>>> At the risk of great bodily harm from Ben, Ani, and others,
>>>>> I again think the use of aprotinin should be limited as much
>>>>> as possible. I know there are cases where the benefit
>>>>> seemingly outweighs the risk. However, the mounting
>>>>> literature against it is becoming increasingly compelling. In
>>>>> addition, my own impression, made years before any of this
>>>>> came out, was that the drug increased the risk of ATN. I'm
>>>>> also convinced that this has the potential to be the Vioxx of
>>>>> cardiac surgery. All I can say is you guys who continue to
>>>>> indiscriminantly use it have got some really big ones.
>>>>> Hal
>>>>>
>>>>>
>>>>> -----Original Message-----
>>>>> From:
>>>>> prasannasimha at gmail.com<mailto:prasannasimha at gmail.com<mailto:pras
>>>>> an
>>>>> nasimha at gmail.com<mailto:prasannasimha at gmail.com>>
>>>>> To: OpenHeart-L at lists.hsforum.com<mailto:OpenHeart-
>> >>> L at lists.hsforum.com<mailto:OpenHeart-
>>>>> L at lists.hsforum.com<mailto:OpenHeart-L at lists.hsforum.com>>
>>>>> Sent: Sat, 18 Nov 2006 1:00 PM
>>>>> Subject: Re: [HSF] Aprotinin
>>>>>
>>>>>
>>>>> Very Sorry used Aprotinin on my redo - can't help using it
>>>>> selectively !!
>>>>> Prasanna
>>>>>
>>>>> Ajit Damle wrote:
>>>>>
>>>>>> Journal club critique >
>>>>>> A disheartening story: Aprotinin in cardiac surgery >
>>>>>> Lien M, Milbrandt E
>>>>>>
>>>>>> Critical Care, 2006 10:317 ( 8 November 2006 )
>>>>>>
>>>>>>
>>>>>> Journal club critique
>>>>>>
>>>>>>
>>>>>> A disheartening story: Aprotinin in cardiac surgery
>>>>>>
>>>>>> Marcus Lien1 and Eric B Milbrandt2 >
>>>>>> 1Clinical Fellow, Department of Critical Care Medicine,
>>>>>> University of
>>>>>> Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
>>>>>>
>>>>>> 2Assistant Professor, Department of Critical Care Medicine,
>>>>>> University of
>>>>>> Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
>>>>>>
>>>>>>
>>>>>> Critical Care 2006, 10:317 doi:10.1186/cc5072
>>>>>>
>>>>>>
>>>>>>>
>>>>>>>
>>>>>> Evidence based medicine journal club critique edited by E B
>>>>>> Milbrant
>>>>>>
>>>>>>
>>>>>> The electronic version of this article is the complete one
>>>>>> and can be found
>>>>>> online at: http://ccforum.com/content/10/6/317<http://
>>>>>> ccforum.com/content/10/6/317<http://ccforum.com/content/
>>>>>> 10/6/317<http://ccforum.com/content/10/6/317>>
>>>>>>
>>>>>>
>>>>>> Published 8 November 2006 >
>>>>>>
>>>>>> C 2006 BioMed Central Ltd
>>>>>>
>>>>>> Citation
>>>>>>
>>>>>> Mangano DT, Tudor IC, Dietzel C: The risk associated with
>>>>>> aprotinin in
>>>>>> cardiac surgery. N Engl J Med 2006, 354:353-365 [1].
>>>>>>
>>>>>>
>>>>>> Background
>>>>>>
>>>>>>
>>>>>> The majority of patients undergoing surgical treatment for ST-
>>>>>> elevation
>>>>>> myocardial infarction receive antifibrinolytic therapy to
>>>>>> limit blood loss.
>>>>>> This approach appears counterintuitive to the accepted
>>>>>> medical treatment of
>>>>>> the same condition - namely, fibrinolysis to limit
>>>>>> thrombosis. Despite this
>>>>>> concern, no independent, large-scale safety assessment has
>>>>>> been undertaken.
>>>>>>
>>>>>>
>>>>>> Methods
>>>>>>
>>>>>>
>>>>>> Design and setting
>>>>>>
>>>>>>
>>>>>> Prospective observational cohort study in 69 institutions in
>>>>>> North and South
>>>>>> America, the Middle East, Europe, and Asia.
>>>>>>
>>>>>>
>>>>>> Subjects
>>>>>>
>>>>>>
>>>>>> 4374 patients undergoing coronary-artery revascularization.
>>>>>> All patients
>>>>>> were >18 years old and completed a pre-surgery interview.
>>>>>> Patients were
>>>>>> classified as undergoing primary surgery (no previous heart
>>>>>> surgery and no
>>>>>> other surgery besides a coronary artery bypass graft), or
>>>>>> complex surgery
>>>>>> (all other surgery).
>>>>>>
>>>>>>
>>>>>> Intervention
>>>>>>
>>>>>>
>>>>>> None.
>>>>>>
>>>>>>
>>>>>> Measurements
>>>>>>
>>>>>>
>>>>>> The authors prospectively assessed three agents (aprotinin
>>>>>> [1295 patients],
>>>>>> aminocaproic acid [883], and tranexamic acid [822]) as
>>>>>> compared with no
>>>>>> agent (1374 patients) with regard to serious cardiovascular,
>> >>>> renal, and
>>>>>> cerebrovascular outcomes by propensity and multivariable
>>>>>> methods.
>>>>>>
>>>>>>
>>>>>> Results
>>>>>>
>>>>>>
>>>>>> In propensity-adjusted, multivariable logistic regression (C-
>>>>>> index, 0.72),
>>>>>> use of aprotinin was associated with a doubling in the risk
>>>>>> of renal failure
>>>>>> requiring dialysis among patients undergoing complex coronary-
>>>>>> artery surgery
>>>>>> (odds ratio, 2.59; 95 percent confidence interval, 1.36 to
>>>>>> 4.95) or primary
>>>>>> surgery (odds ratio, 2.34; 95 percent confidence interval,
>>>>>> 1.27 to 4.31).
>>>>>> Similarly, use of aprotinin in the latter group was
>>>>>> associated with a 55
>>>>>> percent increase in the risk of myocardial infarction or
>>>>>> heart failure (P <
>>>>>> 0.001) and a 181 percent increase in the risk of stroke or
>>>>>> encephalopathy (P
>>>>>> = 0.001). Neither aminocaproic acid nor tranexamic acid was
>>>>>> associated with
>>>>>> an increased risk of renal, cardiac, or cerebral events.
>>>>>> Adjustment
>>>>>> according to propensity score for the use of any one of the
>>>>>> three agents as
>>>>>> compared with no agent yielded nearly identical findings. All
>> >>>> the agents
>>>>>> reduced blood loss.
>>>>>>
>>>>>>
>>>>>> Conclusion
>>>>>>
>>>>>>
>>>>>> The association between aprotinin and serious end-organ
>>>>>> damage indicates
>>>>>> that continued use is not prudent. In contrast, the less
>>>>>> expensive generic
>>>>>> medications aminocaproic acid and tranexamic acid are safe
>>>>>> alternatives.
>>>>>>
>>>>>>
>>>>>>>
>>>>>> The medical and surgical approaches to acute ST-elevation
>>>>>> myocardial
>>>>>> infarction present an interesting paradox. The medical
>>>>>> approach focuses on
>>>>>> fibrinolytic therapy. Due to concerns over bleeding, the
>>>>>> surgical approach
>>>>>> avoids fibrinolytic agents and instead uses agents that
>>>>>> mitigate bleeding,
>>>>>> so called antifibrinolytic agents, which include aprotinin,
>>>>>> aminocaproic
>>>>>> acid, and tranexamic acid. These agents were generally
>>>>>> considered safe based
>>>>>> on a number of secondary analyses of studies that were not
>>>>>> primarily
>>>>>> intended to assess safety. These relatively small studies
>>>>>> were underpowered
>>>>>> to detect adverse events and did not involve head-to-head
>>>>>> comparisons of the
>>>>>> commonly used antifibrinolytic agents. Animal studies
>>>>>> suggest that these
>>>>>> agents have the potential to cause ischemic damage to
>>>>>> multiple organ systems
>>>>>> and small, largely single-center studies have suggested
>>>>>> increased graft
>>>>>> thrombosis and renal dysfunction [2-6]. Ideally, the safety
>>>>>> of these agents
>>>>>> would be compared in a large, multi-center, randomized
>>>>>> controlled trial.
>>>>>> However, because their use is embedded in practice and
>>>>>> because regulatory
>>>>>> approval of these agents differs by country, conducting such
>>>>>> a trial will be
>>>>>> difficult if not impossible.
>>>>>>
>>>>>>
>>>>>> To address the safety of these agents for cardiopulmonary
>>>>>> bypass surgery,
>>>>>> Mangano and colleagues [1] conducted a large, prospective,
>>>>>> observational
>>>>>> cohort assessing aprotinin, aminocaproic acid, and
>>>>>> tranexamic acid as
>>>>>> compared to no agent in 4374 patients undergoing
>>>>>> revascularization. Because
>>>>>> this was a prospective study, the authors were able to
>>>>>> collect a wealth of
>>>>>> clinical information, including approximately 7500 data
>>>>>> fields per patient.
>>>>>> This permitted consideration of variables that might
>>>>>> influence both choice
>>>>>> of antifibrinolytic agent and clinical outcome. The authors
>>>>>> used a
>>>>>> propensity score based on 45 treatment-selection covariates and
>>>>>> multivariable modeling to control for baseline differences
>>>>>> between groups.
>>>>>> In doing so, they found that aprotinin, but not aminocaproic
>>>>>> acid or
>>>>>> tranexamic acid, was associated with serious cardiovascular,
>>>>>> renal, and
>>>>>> cerebrovascular adverse events. Furthermore, a dose-response
>>>>>> relationship
>>>>>> was demonstrated, strengthening the inference of causality.
>>>>>>
>>>>>>
>>>>>> The main weakness of this study is that the authors failed to
>> >>>> report details
>>>>>> of the surgery itself, such as whether the surgery was on
>>>>>> vs. off-pump, time
>>>>>> on pump, and number of vessels bypassed. These variables are
>>>>>> likely to
>>>>>> influence not only choice of antifibrinolytic agent but also
>>>>>> outcome, and
>>>>>> are, therefore, a source of indication bias that could
>>>>>> reflect unfavorably
>>>>>> on aprotinin.
>>>>>>
>>>>>>
>>>>>> Based on the results of this study and those of another
>>>>>> observational study
>>>>>> suggesting renal toxicity [7], the United States Food and Drug
>>>>>> Administration (FDA) held an advisory committee meeting
>>>>>> September 21, 2006
>>>>>> to consider the cardiovascular safety of aprotinin. Because
>>>>>> of concerns
>>>>>> about the methodology of the study by Mangano and colleagues
>>>>>> and because it
>>>>>> was the only study to suggest cardiovascular adverse events
>>>>>> [8], the
>>>>>> advisory committee concluded that there was insufficient
>>>>>> evidence to support
>>>>>> changing the cardiovascular safety labeling of the drug.
>>>>>> However, just six
>>>>>> days after the committee met, it was revealed that the
>>>>>> drug's manufacturer,
>> >>>> Bayer, had preliminary results from an observational study of
>>>>>> 67,000 cardiac
>>>>>> bypass patients that suggested aprotinin was associated with
>>>>>> increased risk
>>>>>> of death, renal dysfunction, congestive heart failure, and
>>>>>> stroke [9]. The
>>>>>> FDA subsequently issued a statement indicating it was unaware
>>>>>> of this study
>>>>>> when the advisory committee met and that it is evaluating
>>>>>> the results of
>>>>>> this study and the potential implications for the use of
>>>>>> aprotinin [10]. In
>>>>>> the mean time, the FDA suggests that physicians who use
>>>>>> aprotinin should
>>>>>> carefully monitor patients for the occurrence of toxicity,
>>>>>> particularly to
>>>>>> the kidneys, heart, or brain, and promptly report observed
>>>>>> adverse events.
>>>>>> They go on to recommend that physicians should consider
>>>>>> limiting aprotinin
>>>>>> use to those situations where the clinical benefit of
>>>>>> reduced blood loss is
>>>>>> essential to medical management of the patient and outweighs
>>>>>> the potential
>>>>>> risks.
>>>>>>
>>>>>>
>>>>>> Recommendation >
>>>>>>
>>>>>> The weight of evidence suggests that aprotinin increases the
>>>>>> risk for a poor
>>>>>> outcome among patients undergoing cardiac operations. Not
>>>>>> only is this drug
>>>>>> very expensive, it seems to be toxic. Although the risk of
>>>>>> excessive
>>>>>> bleeding is certainly a cause for concern in certain
>>>>>> patients, and treatment
>>>>>> with aprotinin can decrease blood loss in selected patients,
>>>>>> data are
>>>>>> lacking to show that administration of this agent actually
>>>>>> improves
>>>>>> survival.
>>>>>>
>>>>>>
>>>>>> Competing interests
>>>>>>
>>>>>> The authors declare that they have no competing interests.
>>>>>>
>>>>>>
>>>>>>>
>>>>>> 1. Mangano DT, Tudor IC, Dietzel C: The risk associated with
>>>>>> aprotinin in
>>>>>> cardiac surgery.
>>>>>>
>>>>>> N Engl J Med 2006, 354:353-365. >
>>>>>>
>>>>>> 2. Cosgrove DM III, Heric B, Lytle BW, Taylor PC, Novoa R,
>>>>>> Golding LA,
>>>>>> Stewart RW, McCarthy PM, Loop FD: Aprotinin therapy for
>>>>>> reoperative
>>>>>> myocardial revascularization: a placebo-controlled study.
>>>>>>
>>>>>> Ann Thorac Surg 1992, 54:1031-1036.
>>>>>>
>>>>>>
>>>>>> 3. D'Ambra MN, Akins CW, Blackstone EH, Bonney SL, Cohn LH,
>>>>>> Cosgrove DM,
>>>>>> Levy JH, Lynch KE, Maddi R: Aprotinin in primary valve
>>>>>> replacement and
>>>>>> reconstruction: a multicenter, double-blind, placebo-
>>>>>> controlled trial.
>>>>>>
>>>>>> J Thorac Cardiovasc Surg 1996, 112:1081-1089
>>>>>>
>>>>>>
>>>>>> 4. Feindt PR, Walcher S, Volkmer I, Keller HE, Straub U,
>>>>>> Huwer H, Seyfert
>>>>>> UT, Petzold T, Gams E: Effects of high-dose aprotinin on
>>>>>> renal function in
>>>>>> aortocoronary bypass grafting.
>>>>>>
>>>>>> Ann Thorac Surg 1995, 60:1076-1080 >
>>>>>>
>>>>>> 5. Sundt TM III, Kouchoukos NT, Saffitz JE, Murphy SF,
>>>>>> Wareing TH, Stahl
>>>>>> DJ: Renal dysfunction and intravascular coagulation with
>>>>>> aprotinin and
>>>>>> hypothermic circulatory arrest.
>> >>>>
>>>>>> Ann Thorac Surg 1993, 55:1418-1424 >
>>>>>>
>>>>>> 6. Umbrain V, Christiaens F, Camu F: Intraoperative coronary
>>>>>> thrombosis:
>>>>>> can aprotinin and protamine be incriminated?
>>>>>>
>>>>>> J Cardiothorac Vasc Anesth 1994, 8:198-201 >
>>>>>>
>>>>>> 7. Karkouti K, Beattie WS, Dattilo KM, McCluskey SA, Ghannam
>>>>>> M, Hamdy A,
>>>>>> Wijeysundera DN, Fedorko L, Yau TM: A propensity score case-
>>>>>> control
>>>>>> comparison of aprotinin and tranexamic acid in high-transfusion-
>>>>>> risk cardiac
>>>>>> surgery.
>>>>>>
>>>>>> Transfusion 2006, 46:327-338 >
>>>>>>
>>>>>> 8. Hughes S: Aprotinin safety again in spotlight as new
>>>>>> study suggests
>>>>>> increased cardiac events.
>>>>>>
>>>>>> http://www.medscape.com/viewarticle/545400<http://
>>>>>> www.medscape.com/viewarticle/545400<http://www.medscape.com/
>>>>>> viewarticle/545400<http://www.medscape.com/viewarticle/
>>>>>> 545400>> >
>>>>>> October 2, 2006 >
>>>>>> 9. Harris G: FDA says Bayer failed to reveal drug risk study.
>>>>>>
>>>>>> [http://www.nytimes.com/2006/09/30/health/30fda.html] New
>>>>>> York Times >
>>>>>>
>>>>>> 10. US Food and Drug Administration: FDA Public Health
>>>>>> Advisory: Aprotinin
>>>>>> Injection (marketed as Trasylol).
>>>>>>
>>>>>> [http://www.fda.gov/cder/drug/advisory/aprotinin20060929.htm] >
>> >>>> September 29, 2006 >
>>>>>>
>>>>>> _______________________________________________
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>
> --
> Ben Bidstrup FRACS FRCSEd FEBCTS
> Consultant Cardiothoracic Surgeon
> _______________________________________________
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