Do something even if it's wrong? The case against unfractionated heparin

In this morning's press conference, Dr Gilles Montalescot of Paris presented the ATOLL trial demonstrating that enoxaparin when compared with heparin produced a statistically nonsignificant decrease in the primary composite end point of death, complications of MI, and non-CABG major bleeding at 30 days, but it did result in a significant 43% reduction in the triple ischemic end point of death, reinfarction, and urgent revascularization. I walked to the microphone and made the point that the reason that so many are supportive of utilization of UFH is that when things go wrong like "no re-flow" or the patient exhibits "TIMI-slow" flow in the cath lab, one can check an ACT and give more heparin. (Anecdotally, things seem to get better, and the patient gets off the table and goes back to the ICU.)  "So, what exactly do you do when you've given enoxaparin and you have no-reflow or slow-flow phenomenon?" I asked. Although he didn't exactly answer my question, he did provide an answer that was far more profound than what I had bargained for. He replied, "Checking the ACT really doesn't help with outcomes." Although it wasn't the answer I was looking for, it is the answer to a far greater question: "Why are we still clinging to heparin when we have better solutions with lower bleeding rates and less ischemia?" Why don't we do what Gregg Stone has been telling us for years and utilize bivalirudin, which I previously referred to long ago as being as "unappealing as your mother's broccoli"? (Embarrassing as it is to admit).

In medicine, particularly cardiology, we have the habit of doing things just because they've been done and because we are comfortable with it. We'll hold onto it so tightly that we'd sooner fight a mountain lion than let it go. Case(s) in point: Until last year, never in the history of furosemide utilization had separate protocols been studied, despite the fact that "IV Lasix" is ordered a gazillion times per hour in every ER and ICU in the universe. Here's another: Try to find a large-scale trial discussing the best time increments for utilization of repetitive sublingual nitroglycerin or even a dose-finding trial, randomized and controlled.

Today, we also heard from Dr Stephanie Schulz of Munich who compared low-weight UFH at a dose of 100 U/kg with high-dose UFH at 140 U/kg. Not surprisingly, the bleed rates were lower in the low-dose group, and it was noninferior to bivalirudin with regard to net clinical outcome. UFH dosing has not been studied intensely in elective PCI "since 1996," according to Dr Schulz, and long since, we've thrown multiple other antiplatelet drugs, GP2b3as, and a whole host of add-ons like fish oils, statins, everolimus, sirolimus, and will throw a whole host of other "limuses" coming down the pike into the mix. If we wouldn't bake a cake that way, we shouldn't concoct our procedural cocktails in the same manner. Just like my brother, (the fabulous cook that he is) tells me, "If you don't follow the recipe for what you are making, you won't get wind up with what you are 'making.' " I just want to shout aloud (to myself included), "C'mon people, the cath lab isn't a meth lab! What we put into our anticoagulation regimens really matters!"

I'm so comfortable with heparin that I could order it with my eyes closed, though some would contend that this is exactly what all of us are doing. I don't even have to calculate the dose. I wrote the protocol at our local hospital for monitoring PTTs based on a whole host of other protocols. We never updated it for two decades until this past year when our pharmacy department took the bull by the horns (and were courteous to ask me to have some input into it, which really wasn't necessary).

My point to this rambling blog? All of us, whether we are angiographers or interventionalists, should take the time to sit down and examine the issue of anticoagulation at our hospitals. Are we still blasting patients with thousands of extra and unnecessary units of heparin? If so, we'd better consider all of the issues.

With regard to anticoagulation dosing regimens in the cath lab, it's time to admit that doing something "even if it's wrong" is still just "plain old wrong."

See also:

Your comments

	Do something even if it's wrong? The case against unfractionated heparin
	# 1 of 3	September 1, 2010 12:41 (EDT)
	Stephen Algeo	Melissa- I agree the current study looks promising but note that most procedures were done from the radial approach. I am always queasy about lovenox for procedures done from the femoral artery- when do you pull the sheath if closure is not feasible? We have seen a fair amount of bleeding complications in patients on lovenox who undergo angiography. As regards angiomax, I think the data in favor of this drug is less robust than most people think. Take Horizons AMI for instance; a study so flawed it should never have been published in my opinion. Two thirds of the patients in this trial recieved a full dose of heparin before randomization! How did this get by the NEJM reviewers? The authors in the original publication said this made no difference in outcomes but later revealed that for angiomax patients who did not receive the additonal heparin stent thrombosis rates at 24 hrs were 2.5%! They now reccomend that pts get full dose heparin in addition to angiomax, but most people seem unaware of this.
	# 2 of 3	September 1, 2010 04:42 (EDT)
	Melissa	Stephen, Thanks for pointing out those very important aspects of the anticoagulation topic.  I confess that the only time I ever use enoxaparin is when a patient  is awaiting an adequate INR for atrial fib or DVT or comes in on a weekend and I know I'm not cathing until "Monday". I admit, I do switch to Heparin the night before I cath them and I've never had a case of unexplained bleeding when I do that though I know it's frowned upon. I don't think folks really take the time to figure out how to switch. I always just start a heparin drip 12 hours from the last  enoxaparin dose. I don't pull sheaths on enox either.   Would have been interesting to hear the sub analysis of how the femoral access only patients did. I didn't hear it presented it but jet lag at this point could have had a bit of an  impact!   My opinion regard which cocktails are best for what indication keep evolving....... Thanks for posting! Melissa
	# 3 of 3	September 25, 2010 03:38 (EDT)
	pw	In fact ATOLL just demonstrate that IV enoxaparine + sub cutaneous enoxaparine for 24-48 h is better than IV HNF+ subcutaneous or continuous HNF for 24-48. Actually ATOLL DO NOT SHOW that IV enoxaparine (alone) is better than IV bolus of HNF.  If you give an bolus of HNF before and in the cath lab and after subcutaneous enoxaparine fot 24-48 h you keep the advantage of both HEPARIN. To demonstrate that IV enoxaparine is more potent than IV HNF you must show for example that TIMI flow is better just after, on angiography before angioplasty (may be it is the case but we don't have read this data just now). We know that HNF is not good after more than a few hours (you just get thrombi and hemorrhages) and that enoxaparine is better for a "long" time. ATOLL mix short and "long" effect of both heparin: it is not fair for bolus of HNF and can't prove that one is the best!      we are waiting the data If you get a low flow it not useful to check ACT, better use intracoronary héparine,isoptine, reopro ( After trying to prevent it by thrombi aspiration, post conditionning,etc.) PW

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