Clopidogrel/heparin for ACS

[Smash]

Good morning. I was just wondering how many here have either clopidogrel (Plavix) or heparin for use in cases of suspected ACS?

If you do, is this used via standing order or physician contact? What are the protocols or parameters around using either of these?

Finally, (and most importantly) what do you know of the efficacy and safety of either of these drugs?

Thanks

Smash

 

[Shishkabob]

We have Heparin, and it's a standing order at 60u/kg up to 4,000u. It's used in suspected cardiac chest pain.


Most of the studies (only a couple..) I've read have shown a better increase in morbidity/mortality with the use of Heparin... but the Heparin was always used in conjunction with either ASA or Streptokinase or another thrombolytic, and never just Heparin... so take it what it's worth.

 

[MrBrown]

WFA use both

 

[Smash]

WFA use both

Wellington Free do many things... :glare:

 

[cruiseforever]

Good morning. I was just wondering how many here have either clopidogrel (Plavix) or heparin for use in cases of suspected ACS?

If you do, is this used via standing order or physician contact? What are the protocols or parameters around using either of these?

Finally, (and most importantly) what do you know of the efficacy and safety of either of these drugs?



We will give Plavix in STEMI pts. We have to have an order from Med Control. I know of no problems.

 

[medicsb]

www.pubmed.com is THE place to look for any research done on the use of either drug (or used together). I don't believe that there is any research where either heparin or plavix was the sole intervention, as linuss said.

 

[NomadicMedic]

We have standing orders for both Plavix and Heparin for STEMI.

Heparin is 70 units/kg up to 5000 units. We hold the Heparin if there is history or ongoing bleeding issues.

Plavix is 600mg PO.

 

[Smash]

So has anyone actually read any of the studies that gave us heparin and plavix? Or is it just taken for granted that it is all good?

If anyone has read any of the source data, would you care to share with us what you thought of it?

 

[jrm818]

Jeesh! it sounds like you're trying to subtly imply that there is doubt about the efficacy of heparin or bleedix. It is very clear that when combined with exercise and a daily diet of effective marketing they both achieve their intended purpose extremely well. We are talking about earning money for drug companies, correct?


To be a bit more serious, but only a bit less cynical...

In extremely high risk NSTEMI plavix is rather effective at increasing bleeding, although this increase in bleeding is approximately offset by a decrease in clinically obtuse but awesome sounding endpoints like "refractory, stroke, MI, OR refractory ischemia," although the "offeset" is mostly driven by the least important endpoints.

In beyond-rigorously screened STEMI plavix is extremely good at inserting marketing literature into prestigious journals, but wasn't so good at improving any patient-oriented outcomes. It still makes you bleed. If your Chinese and receive Chinese healthcare you might have a slight reduction in MI that about equals your increase in severe bleeding. If bleeding isn't your thing it might even make you stroke if you stop taking it.

From what I've seen, heparin is extremely good at mimicking the equivocal results of plavix, but isn't nearly so good at generating money for the drug companies.

 

[Smash]

Aha! That was beautiful, thank you!

There was some discussion at work that we should be adding plavix (Bleedix! Love it!) and/or heparin to our ACS care, so I decided to go looking for a bit of data just out of interest.
Suffice to say that I was somewhat disturbed at what I found. In some ways I (cynically) expected plavix to not be that great (just how not great I didn't realise!) but given how long and how merrily heparin has been handed out to all and sundry, I was surprised at just how bad for patients this is too, even though the profit margins are less!

When I have my MI there is no way in hell I will be letting them put me on plavix, that's for sure.

 

[jrm818]

I think I actually borrowed "bleedix" from you...:blush: I think I'll join you in opting out of the kool aid, both flavors!

I shared your surprise at the heparin results. I'm also surprised to hear about the prehospital protocols for plavix/heparin use. Even if you think the data support the use of either drug, the drugs have only been tested in very high risk populations subject to rigorous rule-out criteria. It doesn't seem like anyone who posted has such criteria (if anyone does, I'd be very interested to see it). It seems to me that using either medication in a lower risk population is extremely hazardous, with a high risk of bleeding but a greatly minimized therapeutic effect.

At any rate, I posted this in similar form elsewhere, but a more serious look at the plavix data:

In NSTEMI:

The CURE trial, found here: http://www.nejm.org/...56/NEJMoa010746

On first glance it does seem to indicate benefit with the use of plavix in NSTEMI ACS, but if you read it carefully there is probably no benefit.

1) There was a demonstrated reduction in risk of a combined primary endpoint of MI, Stroke, Death and secondary of those three plus refractory ischemia. Small benefit was seen with this combined endpoint (especially a small reduction in subsequent MI or ischemia), but no decrease in death was found, though the study was not designed to detect a mortality difference (instead relying on the (evil) combined endpoint to imply mortality benefits in advertisements and subsequent publications).

2) This study only includes a small, very high risk, subset of potential ACS cases: those with elevated troponin levels or ECG changes. Initially patients over 60 with history of artery disease were included, but after the first 3000 patients with this criteria only harm was found, and the inclusion criteria was adjusted mid-study (HERETICS!). The exclusion list was rather lengthy as well.

3) Harm was found: bleeding rates went up significantly. I'm not clear on the clinical significance of some of these events, probably because the study isn’t particularly clear on them.

IN STEMI:

The CLARITY-TIMI study, examining addition of clopridogrel to ASA and Fibrinolytics in STEMI: http://www.ncbi.nlm....pubmed/15758000

Really this study is largely the same. Plavix caused a modest improvement in their primary and secondary outcomes, which again were composites of proposed surrogate markers of disease (better blood flow or re-occlusion) or death, and no difference in death was found. The primary action seemed to be on the rate or re-occlusion. There was a slight trend towards increased mortality with plavix, but the study was underpowered to detect such a difference.

This study again had very strict exclusion criteria (half a column!) and the accompanying NEJM editorial suggests that they may have selected low risk patients this time: rate of death and MI were strangely low. The editorial raises other issue as well (no rapid PCI, exclusion issues, etc) and is a good read.

This study showed a lesser increase in bleeding rates than CURE, but in a different population, and I think there might be a trend towards more bleeding in the elderly. Truthfully I got a bit confused with the data interpretation, but I think that's the fault of the study. Unfortunately numbers are a bit lacking (in my relatively uneducated opinion). There are few tables, mostly looking at odds ratios for benefit in different cohorts, but I don't find that tremendously useful. They only measured rates of bleeding within the first 8 days or until the day after angiography, and I would really like to know if there was a bleeding difference at other time points, especially before angiography (particularly since placebo randomized patients receiving stents were placed on plavix, and I"m not sure where they ended up in the analysis) .

The third big trial is the COMMIT trial (no the B-blocker part): http://www.ncbi.nlm....pubmed/16271642

Gigantic. Chinese. Controversial. Maybe externally valid, probably not. Tiny numbers of PCI, probably underutilized thrombolysis, and different drugs than used stateside. Eating may produce lead poisoning.

Even if we accept COMMIT as valid in western practice, the results are similar: modest reduction in a combined death/MI/Stroke endpoint, a bit of a increase in bleeding (albeit less than found in other trials).


Also, there seems to be a rebound effect when ending Plavix. I guess there is a cluster of clinical events which may be related to a hypercoaguable state within a week or so following cessation of treatment. That sort of harm would not be part of the analysis of these studies.



As for Heparin, I’ll rely on much more intelligent and qualified authorities. David Newman and Ashley Shreaves do a great analysis of the heparin in ACS data as an episode of their (absolutely fantastic) podcast here: http://smartem.org/smartem.org/Home.html

The data from that podcast is conveniently presented in the equally fantastic and highly recommended “NNT” website here: http://www.thennt.com/heparin-for-acute-coronary-syndromes

With a nice little blog entry explaining how the Cochrane review got it wrong: http://www.thennt.com/blog/

 

[medicsb]

Interesting analysis! If I have time, I'll have to read up on this issue over the summer.

 

[Addicted2Narcan]

When you say "suspected" cardiac chest pain, how high of an index of suspicion are we talking about before you give someone who might be dissecting a potent anti-coagulant? I'm not trying to knock, I'm honestly curious about your protocols.

We have Heparin, and it's a standing order at 60u/kg up to 4,000u. It's used in suspected cardiac chest pain.


Most of the studies (only a couple..) I've read have shown a better increase in morbidity/mortality with the use of Heparin... but the Heparin was always used in conjunction with either ASA or Streptokinase or another thrombolytic, and never just Heparin... so take it what it's worth.

 

[Smash]

We have Heparin, and it's a standing order at 60u/kg up to 4,000u. It's used in suspected cardiac chest pain.


Most of the studies (only a couple..) I've read have shown a better increase in morbidity/mortality with the use of Heparin... but the Heparin was always used in conjunction with either ASA or Streptokinase or another thrombolytic, and never just Heparin... so take it what it's worth.

I forgot to comment on this, so I'm sorry that this is a semi-necro thread.

The origingal studies that looked at heparin in ACS (unfractionated and LMHW) were carried out in the golden era of trials in the continental US. In all likellihood, given the over-zealous CYA nature of ethics boards now, they would not be able to be carried out.

The 3 main studies all examined heparin, heparin plus aspirin, aspirin alone and placebo, and none of them found any benefit in heparin.

One study (whose author/name escapes me at the moment... it may have been Thoreau, but I could be wrong) actually went above and beyond the call of duty to find a benefit to heparin in ACS. They took averyone who had been in the study and stuck them on a treadmill. Anyone who did not show any evidence of coronary artery disease was then removed from the trial.

This of course biases the study strongly in favour of finding a benefit with heparin, as they remove all the patients who could not possibly have had benefit anyway. In spite of this crazyness, there was still no benefit found!

 

[silver]

Just wanted to add my two cents.

Plavix dosing in the field is actually pretty risky. I would ask an MD before hand. Lets say you give it and activate the cath lab. You get in there, and they realize this patient needs a CABG and not PCI/Stent. That patient is screwed then, and you'll take the heat.

I would always ask MD for permission, so they get bolused but you won't take heat from the cardiologist.

 

[Trevor]

hmmm... While i dont disagree with you, many EDs around me load their patients with Plavix prior to the Cath Lab...

 

[Smash]

hmmm... While i dont disagree with you, many EDs around me load their patients with Plavix prior to the Cath Lab...

That doesn't make it safe or appropriate.

 

[silver]

Some believe that the risk associated is outweighed by the benefit, though there is not definitive research.

Many EDs do load, but there is also an alternative called prasugrel that works much quicker so there isn't a need of doing it as early as possible. It also has a greater risk of bleeding though.

Like I said always ask.