Danish Registry Points to Increased MI After 12 Months With DES, but Optimism Prevails

Shelley Wood

March 26, 2007

March 26, 2007 (New Orleans, LA) - Uncertainly over stent thrombosis with drug-eluting stents has led to a 20% drop in DES use over the past six months in the US but has remained stable, on average, in Europe and Japan, Dr Martin Leon (Columbia University, New York) told a packed session here at the American College of Cardiology (ACC) 2007 Scientific Sessions. But the overall attitude among interventional cardiologists is one of "calm," even as new registry results from western Denmark, also released here today, point to an increased risk of stent thrombosis and MI after 12 months in DES-treated patients.

"I think there's a greater sense of optimism than there was six months ago," Dr R David Anderson (Sarasota Memorial Hospital, FL) told heart wire . "We're still using them in complex patients, but we're a little bit more cautious. . . . . We are backing off, but it's not a wholesale rollback. I think there was a firestorm after the WCC, but that's sort of calmed down a bit."

Leon presented the DES usage data during an i2 Summit session entitled "DES safety: Hype or reality?" Use of DES peaked in the US during the second half of 2006 at approximately 89%, but has dropped to 70% over the past six months. By contrast, DES usage has fluctuated in the UK and Europe but continues to hover just above 50% on average, while Japan has remained constant, at 72% for the past half year. "They don't change for anything," Leon quipped.

The 20% decline in the US, Leon told heart wire , is "an important drop."

"But it's begun to stabilize. I wouldn't argue that the drop is inappropriate; given some of the safety concerns we've seen, it's entirely legitimate. I'm much less bullish than I was a year ago at the ACC in suggesting unrestricted use of DES. We now have enough in the way of safety concerns that I think use should be restricted and considered very carefully in every case. I still think the majority of patients will benefit if you do the preoperative risk/benefit analysis, so a 70% use in the US is very legitimate."

Western Denmark registry results

Dr Michael Maeng (Aarhus University Hospital, Denmark) presented the Danish registry results, including 12000 patients from the western half of the country, during the i2 Summit's first late-breaking clinical-trial session. After 15 months, Maeng said, investigators saw no overall differences in rates of stent thrombosis or death and MI; however, after clopidogrel was discontinued at 12 months, rates of stent thrombosis and MI (but not death), were significantly higher in DES-treated patients.

The results, Maeng agreed, are "consistent" with other recent studies, including the finding that target lesion revascularizations (TLR) were significantly reduced in DES-treated patients.

"Between 12 and 15 months after index PCI, there was a small but significant excess of definite stent thrombosis and MI in the DES group," Maeng said. "The minor risk of very late stent thrombosis and myocardial infarction does not outweigh the benefit of DES after 15 months of follow-up."

The clincher, however, is that 15 months is only a first glimpse of stent safety. "It's a little too early to tell whether there is a difference," session moderator, Dr Alan C Yeung (Stanford University, Palo Alto, CA), commented following the session.

Anderson agreed. "It appears that stent thrombosis is an event that occurs 15 to 18 months later," he told heart wire . "Up to 15 months, if they've only seen a small difference, I'm not sure that's the whole story."

Results from the Danish registry

End point Bare-metal stents (n=8847) (%) DES (n=3548) (%) Adjusted RR p
TLR 7.1 4.6 0.57 <0.001
Overall probable, possible, or definite stent thrombosis* 2.15 1.8 0.92 NS
Definite stent thrombosis, 1215 mo 0.009 0.09 10.9 0.029
Overall death 6.2 4.4 0.90 0.29
Overall MI 3.0 3.2 1.14 0.31
MI, 12–15 mo DNP DNP 4.0 <0.0001

*Based on the Academic Research Consortium definitions of probable, possible, or definite stent thrombosis
DNP=data not presented

Tackling the problems, moving on

During the "hype-or-reality" session, both the expert presentations and audience questions suggested that operators are aware of the stent-thrombosis problem but looking to the future. That future includes high expectations that new devices may help solve the stent-thrombosis problem, but also a renewed commitment to taking better care of patients.

Leon stressed the importance of careful patient selection; consideration of alternative options--bare-metal stents, medical therapy, or CABG; clear communication of risks and benefits to patients; awareness of patients' pretreatment history; and optimal implantation techniques. "We've gotten very sloppy," Leon observed.

Other speakers raised the issue of "bridging" therapies--none evidence-based--to be used if dual antiplatelet therapy needs to be stopped for urgent noncardiac surgery within the first 12 months. Dr George Dangas (Columbia University, New York) proposed stopping dual antiplatelet therapy and starting enoxaparin 1 mg/kg sc bid five days preoperatively, then restarting clopidogrel and aspirin as soon as possible postsurgery. Dr Harry Phillips (Duke University, Durham, NC) provided an alternate option using GP IIb/IIIa inhibitors, after first trying to get a "second opinion"--a surgeon who could be convinced to perform the surgery in the setting of dual antiplatelet drugs.

To heart wire , Anderson said he didn't think bridging therapies were "widely used," but that, in the absence of data to back up either strategy, he might consider using the GP-IIb/IIIa-inhibitor approach. "In a patient who is high risk--who'd either had a prior event, or who had three-vessel stenting--if they needed their dual antiplatelet therapy stopped within the first 12 months, it makes intuitive sense to try this, and I'm not sure there's a huge downside."

Summarizing current guidelines/recommendations for DES implantation at the end of the session, Dr Gregory J Dehmer (Texas A&M School of Medicine, Temple) reminded the audience that a recent joint statement from the ACC, American Heart Association, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association concluded that bridging therapies were unproven and could increase the risk of bleeding.

The complete contents of Heart wire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.

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