[HSF] Aprotinin
Nasser F. Abou'Seada
nfaabouseada at gmail.com
Mon Nov 20 03:19:54 EST 2006
Thanks Ben .... that has been very helpful ...
NFA
> -----Original Message-----
> From: openheart-l-bounces at lists.hsforum.com [mailto:openheart-l-
> bounces at lists.hsforum.com] On Behalf Of Ben Bidstrup
> Sent: Sunday, November 19, 2006 9:26 PM
> To: OpenHeart-L at lists.hsforum.com
> Subject: RE: [HSF] Aprotinin
>
> http://www.fda.gov/ohrms/dockets/ac/cder06.html#CardiovascularRenal
>
> > > do you have a link?
> >
> >NFA
> >
> >> -----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 7:20 PM
> >> To: OpenHeart-L at lists.hsforum.com
> >> Subject: Re: [HSF] Aprotinin
> >>
> >> 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 >
> > > >>>>>>
> >> >>>>>> _______________________________________________
> >> >>>>>> OpenHeart-L mailing list
> >> >>>>>>
> >> >>>>>> Send postings 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>>
> >> >>>>>>
> >> >>>>>> To UNSUBSCRIBE, to CHANGE email address, or to view archives:
> >> >>>>>> http://mmp.cjp.com/mailman/listinfo/openheart-l<http://
> >> >>>>>> mmp.cjp.com/mailman/listinfo/openheart-l<http://mmp.cjp.com/
> >> >>>>>> mailman/listinfo/openheart-l<http://mmp.cjp.com/mailman/
> >> >>>>>> listinfo/
> >> >>>>>> openheart-l>>
> >> >>>>>>
> >> >>>>>> All messages transmitted by the OpenHeart-L are subject to
> >> >>>>>> the policies and > disclaimers posted at:
> >> >>>>>> http://www.hsforum.com/listdisclaim<http://www.hsforum.com/
> >> >>>>>> listdisclaim<http://www.hsforum.com/listdisclaim<http://
> >> >>>>>> www.hsforum.com/listdisclaim>>
> > > >>>>>> -----------------------------------------
> >> >>>>>>
> >> >>>>>> _______________________________________________
> >> >>>>>>
> >> >>>>> OpenHeart-L mailing list
> >> >>>>>
> >> >>>>> Send postings 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>>
> >> >>>>>
> >> >>>>> To UNSUBSCRIBE, to CHANGE email address, or to view archives:
> >> >>>>> http://mmp.cjp.com/mailman/listinfo/openheart-l<http://
> >> >>>>> mmp.cjp.com/mailman/listinfo/openheart-l<http://mmp.cjp.com/
> >> >>>>>
mailman/listinfo/openheart-l<http://mmp.cjp.com/mailman/listinfo/
> >> >>>>> openheart-l>>
> >> >>>>>
> >> >>>>> All messages transmitted by the OpenHeart-L are subject to
> >> >>>>> the policies and disclaimers posted at:
> >> >>>>> http://www.hsforum.com/listdisclaim<http://www.hsforum.com/
> >> >>>>> listdisclaim<http://www.hsforum.com/listdisclaim<http://
> >> >>>>> www.hsforum.com/listdisclaim>>
> >> >>>>> -----------------------------------------
> >> >>>>>
> >> >>>>>
> >>
> __________________________________________________________________
> >> >>>>> __
> >> >>>>> ____
> >> >>>>> Check out the new AOL. Most comprehensive set of free safety
> >> >>>>> and security tools, free access to millions of high-quality
> >> >>>>> videos from across the web, free AOL Mail and more.
> >> >>>>> _______________________________________________
> >> >>>>> OpenHeart-L mailing list
> >> >>>>>
> >> >>>>> Send postings 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>>
> >> >>>>>
> >> >>>>> To UNSUBSCRIBE, to CHANGE email address, or to view archives:
> >> >>>>> http://mmp.cjp.com/mailman/listinfo/openheart-l<http://
> >> >>>>> mmp.cjp.com/mailman/listinfo/openheart-l<http://mmp.cjp.com/
> >> >>>>>
mailman/listinfo/openheart-l<http://mmp.cjp.com/mailman/listinfo/
> >> >>>>> openheart-l>>
> >> >>>>>
> >> >>>>> All messages transmitted by the OpenHeart-L are subject to
> >> >>>>> the policies and
> >> >>>>> disclaimers posted at:
> >> >>>>> http://www.hsforum.com/listdisclaim<http://www.hsforum.com/
> >> >>>>> listdisclaim<http://www.hsforum.com/listdisclaim<http://
> >> >> >>> www.hsforum.com/listdisclaim>>
> >> >>>>> -----------------------------------------
> >> >>>>>
> >> >>>>>
> >> >>>>>
> >> >>>>
> >> >>>> _______________________________________________
> >> >>>> OpenHeart-L mailing list
> >> >>>>
> >> >>>> Send postings 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>>
> >> >>>>
> >> >>>> To UNSUBSCRIBE, to CHANGE email address, or to view archives:
> >> >>>> http://mmp.cjp.com/mailman/listinfo/openheart-l<http://
> >> >>>> mmp.cjp.com/mailman/listinfo/openheart-l<http://mmp.cjp.com/
> >> >>>>
mailman/listinfo/openheart-l<http://mmp.cjp.com/mailman/listinfo/
> >> >>>> openheart-l>>
> >> >>>>
> >> >>>> All messages transmitted by the OpenHeart-L are subject to
> >> >>>> the policies and
> >> >>>> disclaimers posted at:
> >> >>>> http://www.hsforum.com/listdisclaim<http://www.hsforum.com/
> > > >>>> listdisclaim<http://www.hsforum.com/listdisclaim<http://
> >> >>>> www.hsforum.com/listdisclaim>>
> >> >>>> -----------------------------------------
> >> >>>> _______________________________________________
> >> >>>> OpenHeart-L mailing list
> >> >>>>
> >> >>>> Send postings to:
> >> >>>> OpenHeart-L at lists.hsforum.com<mailto:OpenHeart-
> >> >>>> L at lists.hsforum.com>
> >> >>>>
> >> >>>> To UNSUBSCRIBE, to CHANGE email address, or to view archives:
> >> >>>> http://mmp.cjp.com/mailman/listinfo/openheart-l<http://
> >> >>>> mmp.cjp.com/
> >> >> >> mailman/listinfo/openheart-l>
> >> >>>>
> >> >>>> All messages transmitted by the OpenHeart-L are subject to the
> >> >>>> policies and
> >> >>>> disclaimers posted at:
> >> >>>> http://www.hsforum.com/listdisclaim<http://www.hsforum.com/
> >> >>>> listdisclaim>
> >> >>>> -----------------------------------------
> >> >>>>
> >> >>>>
> >> >>>>
> >> >>>
> >> >>> _______________________________________________
> >> >>> OpenHeart-L mailing list
> > > >>>
> >> >>> Send postings to:
> >> >>> OpenHeart-L at lists.hsforum.com<mailto:OpenHeart-
> >> >>> L at lists.hsforum.com>
> >> >>>
> >> >>> To UNSUBSCRIBE, to CHANGE email address, or to view archives:
> >> >>> http://mmp.cjp.com/mailman/listinfo/openheart-l<http://
> >> >>> mmp.cjp.com/mailman/listinfo/openheart-l>
> >> >>>
> >> >>> All messages transmitted by the OpenHeart-L are subject to
> >> >>> the policies and
> >> >>> disclaimers posted at:
> >> >>> http://www.hsforum.com/listdisclaim<http://www.hsforum.com/
> >> >>> listdisclaim>
> >> >>> -----------------------------------------
> >> >>> _______________________________________________
> >> >>> OpenHeart-L mailing list
> >> >>>
> >> >>> Send postings to:
> >> >>> OpenHeart-L at lists.hsforum.com
> >> >>>
> >> >>> To UNSUBSCRIBE, to CHANGE email address, or to view archives:
> >> >>> http://mmp.cjp.com/mailman/listinfo/openheart-l
> >> >>>
> >> >>> All messages transmitted by the OpenHeart-L are subject to the
> >> >>> policies and
> >> >>> disclaimers posted at:
> >> >>> http://www.hsforum.com/listdisclaim
> >> >>> -----------------------------------------
> >> >>
> >> >> _______________________________________________
> >> >> OpenHeart-L mailing list
> >> >>
> >> >> Send postings to:
> >> >> OpenHeart-L at lists.hsforum.com
> >> >>
> >> >> To UNSUBSCRIBE, to CHANGE email address, or to view archives:
> >> >> http://mmp.cjp.com/mailman/listinfo/openheart-l
> >> >>
> >> >> All messages transmitted by the OpenHeart-L are subject to the
> >> >> policies and
> >> >> disclaimers posted at:
> >> >> http://www.hsforum.com/listdisclaim
> >> >> -----------------------------------------
> >> >>
> >> >> _______________________________________________
> >> >> OpenHeart-L mailing list
> >> >>
> >> >> Send postings to:
> >> >> OpenHeart-L at lists.hsforum.com
> >> >>
> >> >> To UNSUBSCRIBE, to CHANGE email address, or to view archives:
> >> >> http://mmp.cjp.com/mailman/listinfo/openheart-l
> >> >>
> >> >> All messages transmitted by the OpenHeart-L are subject to the
> >> >> policies and
> >> >> disclaimers posted at:
> >> >> http://www.hsforum.com/listdisclaim
> >> >> -----------------------------------------
> >> >
> >> >
> >> > --
> >> > Ben Bidstrup FRACS FRCSEd FEBCTS
> >> > Consultant Cardiothoracic Surgeon
> >> > _______________________________________________
> >> > OpenHeart-L mailing list
> >> >
> >> > Send postings to:
> >> > OpenHeart-L at lists.hsforum.com
> >> >
> >> > To UNSUBSCRIBE, to CHANGE email address, or to view archives:
> >> > http://mmp.cjp.com/mailman/listinfo/openheart-l
> >> >
> >> > All messages transmitted by the OpenHeart-L are subject to the
> >> > policies and disclaimers posted at:
> >> > http://www.hsforum.com/listdisclaim
> >> > -----------------------------------------
> >>
> >> _______________________________________________
> >> OpenHeart-L mailing list
> >>
> >> Send postings to:
> >> OpenHeart-L at lists.hsforum.com
> >>
> >> To UNSUBSCRIBE, to CHANGE email address, or to view archives:
> >> http://mmp.cjp.com/mailman/listinfo/openheart-l
> >>
> >> All messages transmitted by the OpenHeart-L are subject to the
policies
> >and
> >> disclaimers posted at:
> >> http://www.hsforum.com/listdisclaim
> >> -----------------------------------------
> >
> >_______________________________________________
> >OpenHeart-L mailing list
> >
> >Send postings to:
> > OpenHeart-L at lists.hsforum.com
> >
> >To UNSUBSCRIBE, to CHANGE email address, or to view archives:
> >http://mmp.cjp.com/mailman/listinfo/openheart-l
> >
> >All messages transmitted by the OpenHeart-L are subject to the policies
and
> >disclaimers posted at:
> >http://www.hsforum.com/listdisclaim
> >-----------------------------------------
>
>
> --
> Ben Bidstrup FRACS FRCSEd FEBCTS
> Consultant Cardiothoracic Surgeon
> _______________________________________________
> OpenHeart-L mailing list
>
> Send postings to:
> OpenHeart-L at lists.hsforum.com
>
> To UNSUBSCRIBE, to CHANGE email address, or to view archives:
> http://mmp.cjp.com/mailman/listinfo/openheart-l
>
> All messages transmitted by the OpenHeart-L are subject to the policies
and
> disclaimers posted at:
> http://www.hsforum.com/listdisclaim
> -----------------------------------------
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