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August 10, 2010 -- 6:15pm PDT

DES 'n' DAPT: The OPTIMIZE Trial and Drug-Eluting Stents
At the Patient Forum on Angioplasty.Org, we keep getting posts from patients who have received a state-of-the-art drug-eluting coronary stent, but who have either not been informed, prior to the procedure, of the need to take one year (minimum) of DAPT -- dual antiplatelet therapy, consisting of clopidogrel (Plavix) plus aspirin -- or, at the least, were not aware of the financial and clinical implications of this drug regimen: a cost of $4/day, deferral of surgery, possible bleeding complications, etc.

Imagine their surprise.

It's an issue that I testified about at the FDA drug-eluting stent safety hearings back in December 2006 -- and it's an issue that still has patients wondering what to do if they can't afford Plavix or need to have a surgical procedure less than a year after stenting. The purpose of those FDA hearings was to clarify safety issues with drug-eluting stents (DES) and to make recommendations as to the optimal duration of dual antiplatelet therapy (DAPT) necessary to reduce the risk of stent thrombosis (blood clotting inside the stent, often resulting in a heart attack). The upshot was that the recommended six months of DAPT was extended to twelve -- however, this was done in the absence of any real clinical data to back up the extension (no trials had been done to assess the optimal length of therapy). So it was a best-guess scenario for patient safety.

That was four years ago. When I recently asked Dr. Eric Topol what we've learned since then, he replied: "Unfortunately, we don't know anything more regarding the appropriate length of dual antiplatelet therapy."

So finally this year the DAPT trial began enrolling patients. DAPT will test whether there is any difference in outcomes between twelve months of DAPT and thirty. This multi-million dollar trial will not complete enrollment until 2013. And its results will only tell us if there is any difference between twelve and thirty months of DAPT. There will be no information about what happens if DAPT is less than a year -- information that might allow patients to stop taking this expensive drug therapy sooner.

And there will be no breakdown in the type of drug-eluting stent -- somewhat unhelpful since several studies have shown that not all drug-eluting stents are alike. First generation DES like Cypher and Taxus will be lumped together with Xience and Endeavor. For example, if a specific drug-eluting stent has a faster healing rate (and in OCT imaging studies, Medtronic's Endeavor had healed more completely at six months than even bare metal stents) -- perhaps there's no need for a year or more of Plavix and aspirin -- at least with certain stents.

Finally, there will be no genetic or platelet function testing, to see if certain patients with genetic variations are more prone to stent thrombosis than others. Why is this important information? Because stent thrombosis is an infrequent event. If it turns out that a specific subset of patients who are unresponsive to clopidogrel are also those who are experiencing the majority of stent thrombosis, then extended DAPT can be prescribed for just those patients...and the vast majority of patients do not need to take these drugs for such a long time, saving significant amounts of money, lessening bleeding complications, etc.

Dr. Topol's take on the DAPT Trial: "I mean it's just crazy for me to think of the amount of resources that are being expended for mega trials like that. The notion that we should treat all patients for X duration is totally crazy. It completely goes against all the evidence that every patient is an individual with a separate biologic story.... I'm amazed that it's going forward." Enough said.

Enter the OPTIMIZE Trial. I wrote about this Brazilian study back in March ("Three Months of Plavix After Stent: When Less May Be More"). The study is now underway and recruiting in 34 locations with over two hundred patients already enrolled. Principal investigator Dr. Fausto Feres told Angioplasty.Org that everyone involved is very excited. After all, finding out that only three months of Plavix and aspirin is sufficient would be highly significant. Stateside, a similar trial is taking place at the Scripps Clinic near San Diego. The SEASIDE Trial has been recruiting and may soon be expanding locations to speed enrollment. It is similar to the OPTIMIZE Trial, except that it will be testing six months vs. twelve. The principle investigators for SEASIDE are reknown cardiologists Paul Teirstein, David Kandzari and Eric Topol. Again, both OPTIMIZE and SEASIDE are being done using only Medtronic's Endeavor zotarolimus-eluting stent, because of its unique healing characteristics.

The results of these trials won't be known for a year or more. Meanwhile it is critically important for patients and physicians alike to be aware of the reality: the drug-eluting stent is a package deal -- it's both a stent and a year of antiplatelet drug therapy. Patients should be made aware of this prior to stent implantation to assure a high degree of compliance with the current guidelines -- and physicians should be sensitive to whether or not their patient will be able to comply, financially or clinically, before deciding on which stent to use.

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