To Grumpy

[Ira]

I have these researches I've been asked by my boss to do, and I've hit a wall. Can you, oh venerated neurologist-subspecializing-in-stroke, advice me on these? I don't quite know kasi how to e-mail you, so dito na lang. A million thanks. :)

A. Prophylactic thrombotics
1. Low-dose aspirin (80-100 mg/d) vs High-dose aspirin for carotid stenosis/lacunar infarctions/CVA prevention - Which one is better longterm? I looked in several journals, and it's basically controversial pa rin. We give 80-100 mg OD but we got a letter from another Yale neurologist (one of our patients went there for a checkup) saying he shifted the px to 325mg TID. We're afraid of soft tissue hematomas and gastric bleeding, so we lowered it back to 100mg OD. I understand that the US doctors give at least 325 mg OD. Any reason for this? Is there anything new about aspirin as prophylaxis? Do you give them to all pxs over a certain age?

2. Clopidogrel vs. Cilostazol- Is it true that recent studies have sort of discredited Cilostazol? What's so great about Clopidogrel?

B. Is there any existing algorithm for the Tx of CVA in DM pxs? Or is it basically just using a different type of IVF compared to non-DMs, and control of their glucose?

[grumpy]

ack! after the flight from hell, ito ang pasalubong mo, ira? work???!!! e-me your addy at awdbm@excite.com. i am sooo lagged . . .

-- georgia: you're a lawyer? how come you never practiced?
ling: practice gives you wrinkles. look at you.

[grumpy]

isa pa, for the ally fans out there:

ling: i knew i shouldn't have taken this job. you people are making me WORK!!

-- kailangan ko ng kape . . .

[batang uliran]

Ira:

I will of course defer the final verdict to Grumpy but he and I have had discussions about this at least once:

1. Regarding aspirin, the standard here in the US is to use one regular ASA daily but that has not been shown conclusively to be better than a baby ASA as far as the relevant outcomes of death, stroke and AMI are concerned. High dose ASA is clearly not superior and in at least one study showed a trend towards worse outcomes.

2. Grumpy is a big fan of clopidogrel but as per official recommendations here in the US, it is considered one of many alternatives to folks who have not done too hot on ASA (failed on it or can't tolerate it). Others are ticlopidine (has bad hematologic side effects including aplastic anemia and TTP) and the combo of dipyridamole. Incidentally, the combo of dipyridamole and ASA has shown in at least some studies to be more effective than ASA alone. Grumpy is not a big dipyridamole fan. :)

The other issues I'm sure Grumpy can answer. After all, baka siya ang nagpalit ng ASA dose sa pasyente mo! He was a storke fellow at Yale from mid 1997 to mid 1999 so blame him! ;)

[Zen]

LOL @ grumpy! More! More! :D
*paging Lush* ;)

[Yoshi]

Ooops, naligaw yata ako. :)

[Ira]

BU: Thanks!!!! We were arguing about the ASA dosage before, kasi from what I got in medline, the researches tend to lean more for 325 mg-1000 mg OD. I asked my friend who's in UConn and she said they give 325 mg TID. I have not encountered anyone practicing in Manila who gives a dose higher than 100 mg OD, though. We weren't sure if the patients were underdosed, particularly those who have hxs of thrombotic events...do you give a higher dose for those with a significant medical history, btw?

Regarding Clopidogrel, it just came out of the local market this year, and we're a little wary on its use pa kasi. Wala pang med reps ang nagpu-push so we really don't get much info on it. We kind of noticed lang that some neurologists have been starting to use it. Di pala siya mainstream...although any alternative would be helpful talaga for patients with a history of bleeding diathesis. As for Persantin+ASA...would you happen to know the journal in which the study came out? :) *pakyut* We only give kasi either Persantin or ASA, but we hardly give more than one. I think it may help if we have at least 2 antithrombotic meds for high risks.

We noticed a LOT of patients here complaining of soft tissue hematomas, and purpuras after ticlopidine tx even at standard doses. We had to decrease their dosages to as low as 1/2 tab q every other day. It's a good drug though for thrombolysis.

grumpy: Welcome back! Are you going to the party on the 4th? :) My email address is ira@pinoymail.com. Thanks in advance! <;g>;

[BadGiRL]

oh god! *hilo* the terms the terms! naiimagine ko na pag nag med talaga ako...ang daming terms!

question: paano nyo namememorize ang terms pati ang name ng gamot pati ang dosage? i've always been curious of how doctors are able to come up with the right medicine and dosage...considering some patients are allergic to this and that....i heard na someone died because he took biogesic daw...tapos allergic pala sya...so dedo sya the next day! kakatakot naman!

* i hope u doctors don't mind me butting in ur conversation with my questions... :) just can't resist e... pls satisfy my curiousity naman...thx! :)

[This message has been edited by BadGiRL (edited 12-02-1999).]

[Ira]

Grumpy: Thanks!!! I'd really appreciate having a hard copy of the CAPRIE study to show the big boss. :) If you're dropping by BU's place, maybe you can send it through nix? Thanks a million again!

[grumpy]

okay, b/u, now you've really done it!!

points to consider:

1. the actual dose of aspirin that is effective for each individual patient is variable. europeans use as little as 25 mg QD and have reported some incremental benefit. however, most of the large studies performed on aspirin in stroke have used 325 mg daily with demonstrated benefit, and no significant increment in bleeding risk compared to low dose aspirin (i.e. less than 80 mg daily). that's why the FDA allowed the labeling change for ASA last year. although high dose aspirin has been shown to increase the hemorrhagic risk if used in primary prevention, there may be patients who need at least 900 mg daily to produce platelet inhibition. kathy helgason of uic did several studies on activated platelet aggregation showing that there are patients whose platelets remained sticky even at 1200 mg per day. quite elegant work. the main problem with all of the antiplatelet agents is the absence of a readily available, repeatable and reliable test to measure effect. platelet aggregation studies are quite expensive and are often lab-dependent.

personally, i tend to use 80 mg daily for people who have smaller frames, i.e. most pinoys. the benefits are definitely present at 80 mg a day, and i am still somewhat skeptical about using doses lower than that. that said, your question addresses several subgroups of patients who should not be treated the same.

in primary prevention, there is little benefit to giving more than 325 mg QD of aspirin, period.

people with carotid stenosis below 40% do not benefit from surgery, and are treated with aspirin and lipid-lowering agents, plus risk factor reduction. there is some benefit to surgery in patients with 50-70% stenosis, but if the patient was asymptomatic to begin with, you can pretty much toss a coin. however, if the stroke is clearly embolic from the stenosis, then surgery is definitely the safer option. high grade stenosis, whether symptomatic or not, i would recommend surgery for. the benefits are NOT as dramatic in asymptomatic patients, but in the philippine setting, the more definitive your treatment while the patient is still following up, the better. very few will return for surveillance ultrasounds twice a year. coumadin is often used as bridge therapy while waiting for surgery.

lacunar infarcts are best treated with just aspirin and risk factor reduction. most of these people are hypertensive, diabetic, hyperlipidemic or a combination of the above.

i'm pretty sure i know who the person that increased it to 325 mg TID is, and he trained at Mass Gen. and no, he's no longer at Yale.


2. b/u makes it sound like i have a "just 'cause" bias for clopidogrel. although dipyridamole has been kicking around for years, the most significant results obtained for dp alone involved stenting in both the cardiac and peripheral circulations. there are several studies from the 70s and 80s that showed it does not have a positive effect on the stroke population. b/u refers to the ESPS 2, which was another attempt by boehringer to keep dp alive after ESPS 1 bombed. it is the only study where dp was shown to be better than aspirin, and ONLY in the combo. it compared 50 of aspirin QD to 400 of dp QD and a combo of 50 of ASA and 400 of dp. the main problem many american neurologists have with this methodology is that the study used small doses of ASA (would have held up better if at least 80) with supramaximal doses of persantine (remember, it's usually only 75 qd/bid). so even if you get a 37% reduction in stroke or death with the combo, it's a comparison that was unfair to aspirin, and is NS if you look at meta-analyses of aspirin using 80-325 mg, where the risk reduction ranges from 33 to 35%, at much lower cost. one of my mentors is an advocate of the combo. i say, prove it to me some more.

3. ticlopidine's 25% advantage over 325 of ASA alone is a relative risk reduction -- absolute risk reduction was 1%. it is expensive at the dose of 250 mg BID, and requires CBC monitoring every 2 weeks for the first 3 months of therapy, and carries the risks he mentioned. clopidogrel is the ticlopidine molecule with an added acetyl group. this minor change gives it a much more favorable side effect profile: somewhat less overall bleeding, much less serious GI hemorrhage, and neutropenia practically similar to aspirin. at 75 mg QD, its easier for patients to take, and doesn't require monitoring, and comes out cheaper. that's why we like it. in CAPRIE (the definitive clopidogrel study), though, AMI reduction from clopidogrel was the greatest, with stroke the least. and even in CAPRIE, aspirin was superior to clopidogrel in preventing MI, although clopidogrel was better in preventing stroke, and was most efficacious in PAD.

4. cilostazol is not used in the u.s. in clinical practice. the studies that were done on cilostazol for cerebral ischemia are severely handicapped by very small sample sizes. the evidence for benefit seems sketchy at best. it is currently being studied as an alternative to ticlopidine in the combination with aspirin post-cardiac stenting, and the results are interesting. at least one study showed a trend toward lipid profile improvement, but that's a positive side effect that will still need to be proven. it seems to work really well in peripheral vascular disease, though. again, extrapolating this to the cerebral vascular bed is really stretching it.

5. diabetics generally suffer from more lacunes than any other population. we don't use IVF with glucose in ANY of our stroke patients, just straight normal saline. we regularly diagnosed diabetics unaware of their condition at least once a month. we went with clinical suspicion on most of them, and confirmed it with serum HbA1C during the admission. glycemic control is very important, as outcomes in people with serum glucose above 200 are much worse. i try to aim for glucose around 160, particularly with large infarcts.

6. treatment for stroke is pretty much tPA at the moment, with intra-arterial lysis available in very few centers. i'm pretty sure you meant housekeeping.

7. lastly, strokologists hate the term CVA. "stroke" was derived from the description of the disease in medieval times, when patients with sudden deficits were "struck down by the hand of God." cerebrovascular accident implies that not much can be done about it, and we don't know what causes it. stroke, or brain attack, is what we're pushing, because we are making progress in diagnosis, treatment, pathophysiology and management, and we want people to get their asses in the ER ASAP. course if you're paralyzed on one side, that makes it pretty damn difficult, doesn't it?

i know that was a mouthful, which really doesn't interest the remainder of the board, but sweeping statements really get my hackles up.

- "ya know what a CVA is? it's when you're walking down the street and yer hit by a carotid artery!"

[This message has been edited by grumpy (edited 12-02-1999).]

[Kamatayan]

Grumpy: Do you do homeworks too ???

[Ira]

THANK YOUUUUUUUUUUU!!!!!!!! :) So we were okay with the 80 mg OD ASA after all...

I'll suggest trying pxs on Clopidogrel, since based on CAPRIE it's superior to ASA in strokes. I better look for the full copy of that study. Although at 75 mg QID...isn't that a problem in terms of px compliance? The advertising literature for Clopidogrel in Medical Observer was suggesting OD.

As for CVA..LOL, sorry. Old habits die hard!

Badgirl: The terms come second nature once you know the meaning. As for drugs, there are only a few basic ones that you really need to remember by heart. It's easy to remember the not-so-basic and the newer ones because they're related naman to the core drugs that need to be understood well.

[Ada]

Sorry, I couldn't resist since all doctors in PEx are in this thread. Just a couple of questions. I watched Patch Adams 2 hours ago and I was just wondering if he's famous in the medical profession, him being radical and all. Also, something Robin Williams said in the movie got to me: "Why do doctors have to be emotionally-detached from their patients?" Lastly, are there many doctors in the Philippines just like him? Are you? I guess I just want someone like him if I were on my deathbed.

[batang uliran]

I think we must provoke Grumpy more often! :)
Folks, for those of you not into medicine like Ira, grumpy and myself are, grumpy's post is an excellent dissertation on stroke prevention and is knowledge possessed by few if any neurologists in the Philippines. He was involved firsthand in many of these stroke trials so he knows of what he speaks! (sorry grumps, just engaging in a little bit of pr). He's embraking on what I'm sure will be successful career as a stroke neurologist in Manila and if you guys have any people with strokes or even any other neurologic problems he's the man to see! Email him at awdbm@excite.com for his clinic hours (coming soon pa lang!) (sorry again grumps - just some more shameless plugging!)

BTW, I'm not pulling anyone's leg and of course I have a technical bias being a doctor and all but I think this is one of the best if not the best post on pinoyexchange so far - it's good enough to be given as a lecture to neurologists with the topic being stroke prevention!

[This message has been edited by batang uliran (edited 12-02-1999).]

[This message has been edited by batang uliran (edited 12-02-1999).]

[Ira]

I agree with BU regarding grumpy's reply. Although I put my foot in it with "CVA" <;g>;, which is his pet peeve pala. But of course, we have to translate his reply in English...maybe BU is up to it? ;)

Hey BU...when are you coming back and establishing a practice here? :)

Ada: I haven't watched Patch Adams, so I wouldn't really know what sort of guy he is. I THINK he's an activist doctor, though, from Connecticut if I'm not mistaken? (paging BU and/or Grumpy..) As for being emotionally detached...I think there is a need to, in order for you to make the right decision on proper medical treatment. It's very hard to give the right management when you're too emotionally bonded to your patients. That's just my opinion, though.

[This message has been edited by Ira (edited 12-02-1999).]

[grumpy]

ira: it's only 75 mg q day not QID for clopidogrel. that's why patients like it. and i've got copies of the studies -- be glad to give you duplicates. don't know if i can make the EB, though. if i can, b/u, do you know if your folks will be home? might as well drop in to see them, since they're in the area.

[CaRaMBa]

Ada, his hospital exists daw talaga. :)

[batang uliran]

Patch Adams is a unique physician in his way and his hospital does exist but from a clinical point of view, he's really not taken seriously by the medical community in the US. He's well sought after though to give thoughts and uplift patient's and doctor's spirits which is a noble cause in itself.

[nix]

Grumpy, my parents won't be there for that night, but it would be nice if you could join us anyway. It'll be a good treat, trust me!

[Ada]

Irabeybe,

I’m afraid I don’t understand how being attached to the patient can cause poor judgement. Shouldn’t it be the other way around? Since you care so much for the patient, wouldn’t you put more effort into finding him a cure? Or am I missing something here?

You really should watch Patch Adams. I think you’ll like it.

[Zen]

*gets dizzy and faints*

Sa Patch Adams at Ally McBeal lang ako maka-relate ah...

[ruff]

yikes, "pinaligaw" ako ni yoshi dito! grumpy, talo mo na ata yung posts nina yoshi at mikoid dati about foreign land ownership. hehehehe! keep up the good work. i hope next time, maintindihan rin ko what i read. =)

[This message has been edited by ruff (edited 12-02-1999).]

[Ira]

Adavevi: Let me give you a morbid example: Let's say you have a terminal patient. If you are too attached to him, you might not be objective enough to realise that maybe you've done everything, and that enough's enough. Sometimes you just have to know when to quit. Know what I mean? And familiarity breeds contempt--sometimes getting too chummy with a patient makes a doctor vulnerable to being pushed around by the patient. I'm not putting Dr. Adams down--his calling is noble, but medical doctors who are giving treatment are primarily paid to objectively cure a patient, not to hold their hands. Of course, that doesn't mean that you hold back on compassion. I'm not quite sure to what extent Dr. Adams pushed this, but I'd guess he was too emotionally attached.

Grumpy: Can you possibly e-mail me your real name, if you don't mind? I talked to my boss awhile ago about your reply, and he was suitably impressed. I mentioned that you're already affiliated with SLMC and TMC, and since he's the head of NS in both hospitals, plus the co-director of the Institute of Neurosciences in SLMC, he wants to know who you are. He asked me your real name, ang sabi ko "Si Grumpy". Di ata impressive ang Dr. Grumpy eh. :D Thanks!

[This message has been edited by Ira (edited 12-03-1999).]

[Zen]

Dr. Grumpy has a nice ring to it. ;)

[batang uliran]

Hey grumps, mukhang may trabaho ka na! Sabi na nga meron ka ring mabobola! :)
Seriously, I believe he's more than able to head up a stroke unit. Well, grumps, wag mo kaming kakalimutan pag sumikat ka na!

[CaRaMBa]

Ada: Also, if you're too attached to your patients you might bawl like a baby everytime one dies. Whew, it's good I didn't take up medicine!

[grumpy]

thanks for the support, guys! i'm still half-dead half the day, though, so i don't think i'd come across coherent if ira's boss wants to talk to me. masungitan ko pa! fired before i start ang resulta! <;lol>; hmmm, that might NOT be such a bad idea . . .

[Ira]

grumpy: Nah, he's very nice. He's known in the NS circles as a "ninong" of sorts, in that he goes out of his way to help young physicians about to start out on their own. He's also heading the creation of TMC Neuroscience Unit, together with Drs. Bengzon and Saniel, as well as the future head of neuroscience in Asian Hospital and the Brain Center of the Philippines (the one they're building in the former Lung Center). I'm certain you're bound to meet him in the SLMC Neuroscience Conferences during Mondays 9 am, but hey, I've put in an advance PR work na for you. :) Really, though, Dr. Grumpy doesn't have that impressive ring to it, know what I mean?

[Ira]

Hey grumpy, thanks for the CAPRIE photocopy you dropped off in Nix's place. I really appreciate it. Too bad you couldn't stay. My boss told me he met you awhile ago in the SLMC neuroscience conference...missed that one! :) Anyway, good luck with your practice, I'm sure you're going to be successful. Don't forget us way down here on the totem pole pag nasa taas ka na, ha? :D