Plavix and 2C19 BrewHahHah

Yes,

I am a little slow

Yes,

It has been a long time.

But,

I am back. With a serious hankering to smash some studies. I already pooh pooh'd the Migraine SNP study on Twitter, but the Plavix stuff.....That deserves a blogpost.

To quote a famous caridologist and friend

"If Plavix really didn't work for 30% of patients, why don't we see more in-stent thrombosis?"

Translation: Your science is nice, but how does it fly in the real world?

I have to tell you, at first I couldn't answer. It was a great question. Do a full third of people have that severe failure?

The obvious answer is NO. If 1/3 rethrombosed, we wouldn't be using Drug Eluting Stents.

So what is the answer:

Apparently a BMS (I.E. Plavix maker) funded study investigated this

We hypothesized that the benefits of clopidogrel as compared with placebo would be decreased in persons who carry a loss-of-function CYP2C19 allele and increased in carriers of the gain-of-function *17 allele.

What did this team study?

we examined the efficacy and safety of clopidogrel as compared with placebo according to genotype status among patients in two randomized trials: the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, in which patients with acute coronary syndromes were enrolled, and the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE) A, in which patients with atrial fibrillation were enrolled.

Ok, so they took 2 different populations and bundled them into the same article....

The 2 studies?

CURE-randomized, double-blind, placebo-controlled trial comparing clopidogrel (at a dose of 75 mg per day) with placebo — both in combination with aspirin — among 12,562 patients with acute coronary syndromes without ST-segment elevation.

ACTIVE A- was a randomized, double-blind trial comparing clopidogrel, at a dose of 75 mg per day, with placebo — both in combination with aspirin — for reducing the risk of stroke among patients with atrial fibrillation and at least one additional risk factor for stroke who were not eligible for warfarin therapy.

What did they find? No difference between Poor Metabolizer and Wild Type in secondary and primary outcomes.

So are we wrong with our studies showing 2C19 genotype matters in outcomes?

Probably not.

1st the authors note why.

1. One possible explanation for the divergence between our findings and those of previous studies involving patients with acute coronary syndromes is the difference in the rates of PCI with stenting. Only 18.0% of patients in the CURE population included in our study underwent PCI, and only 14.5% underwent PCI with placement of a stent, as compared with more than 70% in previous studies

2. We cannot definitely exclude the possibility of an interaction in the subgroup of patients who receive stents, particularly those who receive drug-eluting stents, which were not in use at the time of the CURE trial.

3. the ACTIVE A genetic data set contained fewer participants and outcome events than did the CURE data set and therefore had less statistical power.

My take

The ACTIVE A trial to assess the hypothesis was powered at 45% to detect a difference, thus it is a worthless study and should not be included in this analysis.

While I agree that a placebo group may be useful. It is not needed to assess a difference between people using Plavix with normal Plavix metabolism and Poor metabolism. In fact it may even confuse the situation as it introduces further confounding factors not genotyped or phenotyped out.

The authors disagree
First, the inclusion of a randomized placebo group in our analyses reduces various sources of confounding, such as potential pleiotropic genetic effects or population stratification.

Well, did they test or assess for pleiotropic genetic effects? No.

Further, by introducing a study COMPLETELY underpowered to observe and eval the hypothesis into this article, it ONLY creates a false image of scientific validity.

The authors disagree
Third, we observed consistent benefits of clopidogrel, irrespective of CYP2C19 genotype, in two different patient populations, which validates our findings and suggests that they could be generalizable to other populations.

Again to quote the article

Among patients with atrial fibrillation in ACTIVE A, our study had much lower power (45%) to detect a similar interaction.

So why did they include the POORLY POWERED study?

" in two different patient populations, which validates our findings and suggests that they could be generalizable to other populations."

While I laud the effort to have Randomized and Observational versus retrospective efforts. I think we have to be very careful in our study design to make sure

1. We are properly powered to observe differences.
2. That we assess pleoitropic effects, rather than claim to control for them mysteriously.

The Sherpa Says: Why include the second study? It is improperly powered, further the CURE study did not include Drug Eluting Stents! Why? Plavix goes generic in 2011. They did this to save the market......Expect more screwy studies published in NEJM etc. As PGx gains traction, contrarians and Pharm will always fight it.....

Ok, Spam Botted! Prasugrel PLUS 2C19 PM has better outcome.

Alright, so I just found out that I posted a spam bot post. Not from a nice student named Ashley.

Instead what I will post is a subgroup analysis of TRITON TIMI 38. The subgroup analysis? 2C19 PMs and Prasugrel.

Great clinical question-Did the PMs (poor metabolizers) on Prasugrel fare better than the PMs on Plavix.

The obvious answer:
Duh, of course yes.

But Always we need some science and statistics here.

Individuals with a CYP2C19 reduced-metabolizer genotype were estimated to have a substantial reduction in the risk of the composite primary outcome (cardiovascular death, myocardial infarction or stroke) with prasugrel compared to clopidogrel (relative risk 0.57; 95% confidence interval [CI], 0.39 to 0.83).

Ok, so we should screen for PMs? Probably.

What about every other result?

What about the EMs?

For CYP2C19 extensive-metabolizers (EM) ( approximately 70% of the population), however, the composite outcome risks with prasugrel and clopidogrel were not substantially different (relative risk 0.98; 95% CI, 0.80 to 1.20).

The Sherpa Says: We should AT LEAST be identifying the PMs and placing them on Prasugrel. This subgroup analysis shows increased risk while on Plavix. Primum Non Nocere.

99 USD, DNA day and patient letters

Yes,

What a great DNA Day!

Today started with my twitter feed notifying me that 23andMe had dropped their prices to 99 USD today. Which almost had me encouraging people to get testing, until I remembered that 23andSerge would then have your DNA..........FOREVER!

Then I opened my email and read this great note

"Dear Dr. Murphy,

Thank you so very much. I am so lucky to have found your team. Who would have thought my Plavix might not be working for me? Only when you told me about how it could not work did I realize that I might be taking something that is worthless. Thanks for testing me. Now that I am on Effient I feel much safer!

Thank you Dr. Murphy,

You saved my life!"

That's right. A genetic test, may have saved this patient from a heart attack. A genetic test I do regularly. Who has this patient's test result? Not some corporation that will use it for profit. No, just me, who will use it to act medically. While as these other services say explicitly, YOU CANNOT USE IT FOR MEDICINE!!

To be certain, you should not stop your Plavix WITHOUT talking to your doctor first!

Shame on them, their test could save a life. But not according to their TOS.

I will be speaking at the Consumer Genetic Show about precisely this problem and others. I was so surprised that they asked me to speak. Especially after the beating I gave it last year.

But on this DNA Day I am here to tell you, the public is aware now. DNA testing does hold promise, but only when in the right hands.........

The Sherpa Says: Pharmacogenomic testing IS MEDICINE. It is NOT FOR $H!T$ AND GIGGLES! Happy DNA Day!

PGx in DTCG? Doesn't stand up to Useful testing.

HT Don Rule today as well as the ENTIRE Pharmacogenomics Advisory Group that I am a proud member of.

Don wrote this comment a few days ago

"I was curious about what SNPs the DTC companies offer so I wrote a little applet (http://snpweb.cloudapp.net/#/PharmGKBSNPs) to compare them to the SNPs in PharmGKB. It turns out the the Cytochromes are particularly sparse."

Well Don, you are correct. Even more so, as we began to review SNP data it became crystal clear on Monday.

The reason I was pissed about 23andMe doing the CF testing is because they missed hundreds of potential carrier alleles. What was even more so angering when I realized, you could be "tested" by one of these DTCG companies for "Plavix Metabolism" and come up with the absolute wrong answer.

Imagine that. Most people turn to DNA for an "absolute call" but when you don't look for the right SNPs or all of the needed SNPs, you miss a whole bunch.

Quick story. I had this pulmonologist physician, an elder statesman, super smart, Ivy league trained come up to me and say "Hey Steve, can you help me out?"

He is a sleep doctor too. He said "I have been trying to test for this narcolepsy gene and I can't get the right answer"

I said "Sure Dr. X, what do you mean 'keep getting the wrong answer'?"

He Said

"Well I am looking for HLA DQB1 and they keep telling me about this HLA DR, I have sent this test 3 times now and still gotten no information about HLA DQB1."

I did a big 'ol face palm.

Quest, where he had sent the blood, did not test for HLA DQB1

Instead it searched for an imperfect haplotype......

That's the problem. If you don't test for exactly what you are looking for, you will never find it. Nor will you have the correct clinical answer.

If you only test 2 SNPs for CYP 2C19, you will never be able to accurately predict what someone's metabolizer status is.

What people should be using to assess metabolizer status of medications is something like the DMET Plus with additional PCR or another platform. AmpliChip does a nice job, but we have to be serious when it comes to medical care.

You Cannot, I repeat Cannot take the advice from 23andMe when it comes to metabolizer status for Plavix.

Please, please, please listen to me. Even 23andMe states it on their post about Plavix

This DTCG test is not ready to be used in the clinic or even trusted to tell your metabolizer status. Right now, they are not testing enough SNPs for me to be happy with it and use it in the office.

Don't stop your Plavix! Instead go get a clinical pharmacogenomic test done by someone who understands the limitations of the labs.

That drunk who lost their keys is still looking under the lamposts because that is where the light is..........

That is a stupid way to do clinical pharmacogenomics.

The Sherpa Says: Pretending to be clinical without standing up to clinical rigor is a recipe for disaster. I await the lawsuit from in stent thrombosis for the poor sap that trusts 23andMe enough to stop their Plavix.

Ok, Fine, Back to Plavix

Did anyone else see this?

Scripps and Eric Topol are going to be doing testing for 2C19 polymorphisms in their interventional dept.

"Scripps physicians will initially offer the genetic tests to elective stent patients before they undergo their procedures at Scripps Green Hospital. Eventually, Scripps may extend the offering to its other facilities across San Diego County."

I have been prodding Greenwich Hospital to do this.....I hope they do......They could be the El Camino of the East.

What are these guys, Topol et.al going to be doing? "Scripps patients carrying the gene risk variants will be considered for three treatment choices following their stent procedures, each on an individualized basis. Patients will either:

• Be given a routine 75 milligram dose of Plavix with careful surveillance;
• Be given a 150 milligram dose of Plavix, which has recently been shown to be safe and effective in patients showing lack of response to Plavix; or
• Be given the newly approved medicine Effient (prasugrel), which is not affected by the gene variant Cytochrome (CYP) 2C19."

So there you have it. A cutting edge medical facility doing this. I am only all too certain we will see about 20 hospitals follow in their footsteps in 2010.....

The Sherpa Says: Wha? These guys are like a year behind me......I have been doing this since January........

Pharmacogenetic Indication for a Medication?

That's one way to market the newest medication to prevent stroke, heart attack or stent thrombosis.

Wha? Yes, I mean, Prasugrel otherwise known as Effient is FDA approved for use in these patients.

But one thing I was thinking is that, since the FDA put on the insert of Plavix that 2C19 testing may be useful to identify people who will not respond to Plavix (generic Clopidogrel)

Perhaps, the marketing geniuses over at Eli Lilly could use this as an FDA suggestion that these 2C19 people may be better off with Prasugrel.

Yes, it would be one of the most brilliant ways to market pharmacogenomics. I can only imagine the DTC genomics companies salivating over this "We offer the 2C19, test. Act now, save your life." Technically, It actually could. Yes, all the stops would be pulled out and it could potentially save the DTC genomics companies.

You may be asking yourself, "The DTC companies need saving?"

Yes, they do. Face facts, Research revolution is a flop, nowhere near 1000 people per study. Funny how people don't trust google or anyone without proper research accreditation.

Navi is slashing costs and they have a CEO who is the master of running wastelands (i.e. companies where all the bad assets of a VC firm go)
DeCodeMe.....huh?
Pathway and Tru have no marketing budgets and no real scientific staff.......... Seriously here. WTF?

But, if they could get one big hit from Lilly shoving billions into this PGx marketing campaign, they could be ok. Otherwise, I am afraid, they are lost.

For Lilly it would be a huge win too. Why? Imagine being able to pull a full 1/3rd of all patients taking Plavix off and switching them to Effient/Prasugrel. They could, they really, really could.

So now that I have you attention. The big question is , when will Eli Lilly do this? My guess, in the fall.

Mark my words, they WILL DO THIS and it WILL SAVE companies like 23andSergey and Navi. If of course they offer the test. LabCorp, Genelex and Quest all offer the test now.

But here's the rub, if they offer this and say it is used to make a clinical decision, then they will be a part of the healthcare industry......... Oops, forgot to mention that before. Survive and take regulations or Die..........

The Sherpa Says: This would be the most brilliant marketing campaign in the world, Personalized Medicine awareness would be worldwide, and Pharmacogenomics would hit the stage in a major, major way....Thanks Lilly, call me to orchestrate your campaign.....

Great Job Mike! 2C19 meets the grade!

I was flipping through the internal medicine news yesterday when I saw a colleague. Mike Murray, Clinical Chief up at the Brigham who had given me some good advice re: being a fellow and academia......

He and a couple other internal medicine geneticists write a column called "Genetics in Your Practice"

Which is a welcome addition to what my wife and I (Both Internists) believe is one of the best print publications out there for keeping ahead of the curve with IM and subspecialties....

Well,
Mike wrote about Plavix, which, as you know, I have been all over since the studies came out in January showing significant differences in outcomes clinically with patients who cannot activate Plavix. Why was I all over it? Because it had met some criteria which I think will define what a good PGx test is......

I have as of yet failed to detail precisely what these criteria are.....It just so happens, Mike did a brilliant job of it.....So without further ado. Dr. Mike Murray, Internists, ID specialist AND geneticist defining the criteria....

From Internal Medicine News

So, what will bring a breakthrough application in pharmacogenetics? I believe that a true breakthrough into the mainstream will occur when the gene-drug pair has many or all of these characteristics:

▸ A widely used drug. There are currently some excellent examples of gene-drug pairs as models for the clinical application of pharmacogenetics; however, they happen to be with drugs used by only a small number of subspecialists. A true breakthrough application will need to be a widely used medication.

▸ An “essential” drug. Although we may eventually get to pharmacogenetics testing for almost all medications, a true breakthrough application will not be for a drug for which the application is usually elective (e.g., onychomycosis therapy) or for a drug that has equivalent substitutes inside or outside of the class (e.g., a diuretic for hypertension).

▸ Potentially severe consequences from use of the drug without pharmacogenetics guidance. The motivation for using a pharmacogenetics approach is mainly safety or efficacy. The breakthrough application will need to help the prescriber avoid morbidity or mortality associated with side effects or ineffective treatment.

▸ A narrow therapeutic window. Aminoglycoside antibiotics are classic examples of drugs with a narrow therapeutic window, where underdosing can lead to disease progression and overdosing can cause adverse effects.

▸ Pharmacoeconomic advantage. The application of new technology to guide gene-drug decision making will be more attractive for clinical uptake in instances where it offers cost savings.

▸ Straightforward genetic interpretation. Much of current genetic testing deals with complex interpretations of sequence data where variants unique to the individual patient have to be judged as causative, noncausative, or of unknown significance. In 2009 the most straightforward diagnostic genetic testing is based on screening for common variants that confer increased relative risk.

▸ Validated significance of gene-drug pair. There will always be varied levels of confidence in any data set; however, replication of significant correlation in more than one large, well-designed study will be the most likely to be associated with rapid clinical uptake.

This is precisely what Plavix is......And it is precisely why it will lead personalized medicine this year.......Not genome scans, not whole genomes, Plavix pharmacogenomics...... Mike, yet again, you have crystallized criteria which I often find nebulous......

The Sherpa Says: If we judge all tests by this criteria we would be better off.......Imagine how many less tests would be ordered. Bad for business, great for medicine......

Duh!!! For at least 5 years we "knew" this!! PPIs and 2C19

In case you missed my further rants about how everyone on Plavix should be tested for 2C19 polymorphisms, often splice site changes, which could hinder the effect of plavix......Now a big fat , No Duh....comes out in the Journal of the American Medical Association.

Let me lay the ground work.........

Plavix, one of the top 3 medications in the world

1. Prescribed to prevent a second heart attack or stroke


2. Prescribed to prevent a clot forming in a coronary artery stent, which one often receives after having a heart attack


3. Given in patients with PAD

It turns out that in order for this medication to work it needs to be converted from Plavix into its active metabolite. This type of medication is called a Pro-Drug. There are others like this, including tamoxifen and codeine.

Well, the enzyme which converts Plavix to its active metabolite is called CYP 2C19. We have known this since 2000. A professor of mine actually published on this back then. We even knew about so called "Plavix resistance" .

We know theorize that Plavix resistance is mainly due to polymorphisms in CYP 2C19. This has been studied since 2000, but only recently came to major light with articles in Lancet, New England Journal of Medicine......and my rants on this Blog and in Lectures at Yale and Affiliated Hospitals....

Now........the fly in the ointment....

Proton Pump Inhibitors(PPIs) like Prilosec and Protonix........Are available over the counter since they are so "benign"......

Well, we have known and studied since 1997 that Prilosec inhibited 2C19's ability to biotransform other medications.

So what about allof the people taking BOTH Plavix and PPIs? Let me guess.... the results are like the data in 1997!!!!! That patients receiving both medications have little Plavix effect and decreased platelet inhibition.

Well, that was shown in 2006 and even some preliminary data in 2004.

So one has to ask, well why haven't we put anything on the label? Why haven't their been huge warnings....even more so....how many people are on Plavix and PPIs? The pharma companies know.......how come they haven't warned people pre-emptively that there "May be a problem"

The FDA always asks how much evidence is enough.....but now with the study just published in JAMA it is painfully clear.....we have missed the boat by requiring TOO MUCH PROOF!!

What does the study say? Those who are on Plavix and Prilosec are 27% more likely to have a recurrent hospitalization or DEATH from acute coronary syndromes than those NOT ON THIS COMBINATION!!!

AND, 2 of 3 people in this study on Plavix......were ALSO on Prilosec!!!!

This study was a retrospective study which does have limitations, but has me asking why do we have 3 years of data on this combo 2003-2006, when we knew that there may have been a problem back in 2000????

Why didn't we do a better post market analysis?

What's even worse......people advocating pharmacogenomics are getting push back from lazy clinicians who are asking for randomized double blinded studies to PROVE this problem.....

But here's what they don't know.....the pharmacology literature is robust with Pgx data, just as it was with PPI 2C19 inhibition data....Too bad doctors don't read pharmacology literature....

Anecdotally, when I was a resident, I pulled all of my patients off PPIs that were on Plavix. What did I do? I did a med reconciliation and became aware of the possible interaction.....In this case it was NO BIG DEAL to put them on H2 blockers instead......

Primum Non Nocere.......not PRIMUM RANDOM DOUBLE BLINDUM.....

This just pisses me off.........9 years to come to clinical light........That is a damn shame, That may also happen with Prasugrel....

The Sherpa Says: Why do we as physicians wait for a large organization to say stop, when we have the education to figure out from the literature when we should have stopped? Or for that matter, when we should have started......the burden of evidence has been overcome here.....Unlike SNP Scans.......

Prasugrel saves Clopidogrel???

You gotta love it. The other day I was talking to a pharma rep, yes I do speak with them.....and they were all excited about Effient (generic name Prasugrel).

What are these medications and why was the Pharma Rep excited?

Well, you see Plavix(generic name Clopidogrel) which is one of the top 3 selling medications in the world is given to people who have had a stroke or heart attack. This medication is given to prevent another heart attack or stroke......

Also, this medication is given to people who have received stents in their coronary arteries. This is to prevent the stents from clogging up with platelets.......sort of a Drano in a pill so to speak.

It is also given to people who are having an acute heart attack.

These 2 medications are blood thinners. How do these thinners work? They block platelets, in a way similar (but not the same) as Aspirin.

Why was the Pharma Rep excited?

1) Prasugrel is just about ready to be FDA approved for use

2) Prasugrel has a study called Triton-TIMI 38 which shows it is better than Clopidogrel with outcomes

3) 2 studies just came out last month in the New England Journal of Medicine and one in the British Journal Lancet which show that up to 1 in 3 people taking Clopidogrel(Plavix) may have little to no effect from the medication and are at 300 times more risk for ANOTHER heart attack, stroke, or stent clogging by platelets.......And another one this month in the European Heart Journal!!

4) Another study came out showing that Plavix has no effect in patients who are on proton pump inhibitors. Drug Drug interactions are a big deal.....

Why is number 3 a BIG deal? Because it is a polymorphism in CYP 2C19 which reduces proper conversion of Plavix to its active form.

This IS PERSONALIZED MEDICINE!!!!!

We can test patients, avoid a medication or perhaps increase a dose according to genotype and ultimately change the risks of being a poor metabolizer......

Why am I not so HOOO RAAAHHHH for Prasugrel?

Guess what? Prasugrel ALSO requires conversion like Plavix..........it just uses another CYP enzyme.....

What's that you say? Maybe that enzyme isn't screwed up in 1 in 3 people.....

But it is at least present in 7-10% of certain populations and as high as 83% of African Americans!!! I think 83% is pretty high.....what one in three? 33%?

Well, that enzyme is CYP 3A4. Does that sound familiar to anyone? CYP 3A4 is required for some STATINs to be metabolized as well as some immunosuppressants.......Oh and as for drug, drug interactions from CYP3A4 inhibitors....

Here's the list

amiodarone, amprenavir, cannabinoids, cimetadine, clarithromycin, clotrimazole, cyclosporin, delavirdine, diltiazem, ethinylestradiol, erythromycin, fluconazole, fluoxetine, fluvoxamine, indinavir, intraconazole, ketoconazole, metronidazole, mibefradil, miconazole, nefazodone, nelfinavir, nicardipine, norfloxacin, propafol, quinine, ritonavir, saquinavir, sertraline, troleandomycin, verapamil, zafirlukast

The ones that I bolded are medications I have prescribed in the last month......

Looks like we may have a teency Weency reason to be less exuberant......

Here's what I think. The same thing that they found with Plavix, will also be the case with Prasugrel.......

Which means.......We should stop dosing medications without knowing the patient's freaking genotype.....what the hell is wrong with these knuckleheads!!!!!!

The Sherpa Says: If Lilly was wise, they would release these "trade secrets" and let us know how many of their patients in the private trials failed therapy and were CYP3A4 poor metabolizers.....Now OFF to the PMC Clinical Science Committe meeting!

Plavix, Plavix, Plavix

I just finished up giving a Yale Affiliated Hospitals Lecture to a bunch of residents on the topic of pharmacogenomics. Not to toot my own horn, but several residents came up to me and asked......"Why didn't I learn this in medical school?" Even better was the 3rd year medical students who just finished up Pharmacology last year....they said "The EXACT SAME THING".......

Ok, so here's my beef. Why in the hell aren't we teaching this in medical school. I know I have said this before......but what in the hell is going on here? We have data and not just data , but DAMN GOOD data....and instead we are still pumping JakStat pathways down the throats of our second year medical students.....

I have a very big problem here and I need it fixed. Why can't we get physicians who study PgX to teach this? It is simple really, I know many more doctors who like PgX than who like other sides of genetics.....why not let them in to teach these students????

I see no barriers other than cost of paying clinical faculty, which is always the barrier.....

That being said, even with the great Plavix data out there, we still have non believers....

An editorial in the Annals of Internal Medicine hints at it.

Entitled "Personalized genetic Prediction: Too Limited, Too Expensive, or Too Soon?"

It gives me a reason to say bull$h!t

The title is an eye catcher which most busy clinicians won't read, but instead use the title as a guide post for attitudes on this subject....Trust me, I know clinicians who did precisely that.

You see, the problem with this editorial is that it should have been titled "9p21 to predict cardiovascular risk: Too Limited, Too expensive, or Too soon?"

I love how the Annals completely makes a hash of what Personalized Medicine is!

A quote from the editorial

"As these studies show, we are still far from personalized medicine."

I guess Dr. John doesn't see pharmacogenomics as part of Personalized Medicine

Or maybe he just doesn't read the New England Journal of Medicine......

Either way.....this is not a responsible way to publish a journal and disseminate personal opinion.

I personally think it is because the ACP (American College of Physicians) does not have good advice on how best to get its body up to speed on this stuff.

But I know this is not exactly true, because they sponsor Mike Murray's Harvard course on the Genetic Basis of Adult Disease, which has one lecturer on Pharmacogenomics

So why? Why did they fail to include personalized medicine into the ACP meeting?

Why did they let this guy give the opinion that disease prediction was the only thing in personalized medicine?

Why? I have no clue. But I would love to have someone from the ACP tell me.......

Please!

The Sherpa Says: Education, Regulation and Litigation will be the drivers of this field.....Not the Data......That is a damn shame. And yes, I did go to Penn State!

It's coming!!!!! FDA considering changing the label on Plavix

Did you hear? The Food and Drug Administration is in discussions with BMS and Sanofi Aventis to change the label in Plavix.....But here's the rub...

What do they say? The studies definitely show patients are at risk. The question is how many???

With Plavix being the second most prescribed drug in the nation this has left cardiologists jaws agape!

"life just got very confused and much more complex" for cardiologists and patients, said James Calvin, director of cardiology at Rush University Medical Center in Chicago. He added, "We have to start to become very, very aware of how big an issue this is."

This from an article in CNN/Money today!

"Once you know the answer what do you do?" said Douglas Weaver, head of the department of cardiology at Henry Ford Hospital in Detroit and president of the American College of Cardiology. He said there aren't any alternatives to Plavix approved in the U.S. A potential alternative, ticlopidine, is rarely used because it has been associated with serious blood disorders.

Oh, Doctor Weaver, if you only would read the Sherpa, I recently gave you 4 options of things you could do......just because we don't have rock solid evidence behind it doesn't mean we can't do these things....and when the FDA label changes, you better get ready for the trial lawyers!!

"Clearly I think just the blind administration of these drugs is rapidly coming to an end," said Paul Gurbel of Baltimore's Sinai Hospital

That's music to my ears!!!!

To quote my very first post:

Ok,

So I have no idea where to begin. Which is why I will just start with the Stats.......

• Only 17% of patients with familial colon cancer risk were referred to appropriate genetic counseling according to a study at Harvard.


• Prenatal counseling is not offered 9 of 10 women who meet indications!
  


• Only 37% of MDs know that BRCA genes can be passed by the father!

We have a lot to cover and I look forward to sharing my solution to this huge problem. How in the world can we expect to implement Personalized Medicine in all its glory without having some Genome Savvy physicians? Oh....Those geneticists? Too bad almost 90 percent are pediatricians and have no clue what ischemic heart failure is. (Or Plavix)

The Sherpa Says: I see that lawsuit creeping closer and closer......We need some educators and damn fast! The durg-drug interaction with PPIs has been a possibilty for years, the gene-drug interaction too....now what about the gene-drug-drug????