ACC 2009: Largest-Ever Real-World Study Lays to Rest Safety Concerns Surrounding DES

from <a href="" target="_blank">Heart<i>wire</i></a> &#151; a professional news service of WebMD

March 28, 2009

March 28, 2009 (Orlando, FL) – Patients receiving drug-eluting stents (DES) had significantly better clinical outcomes than their counterparts who received bare-metal stents, without an increase in bleeding or stroke, according to new results from the largest ever real-world study to look at this issue [1]. Dr Pamela S Douglas (Duke Clinical Research Institute, Durham, NC) presented the findings at a late-breaking clinical-trials session here at the American College of Cardiology (ACC) 2009 Scientific Sessions today, and they were simultaneously published online in the Journal of the American College of Cardiology.

DES were swiftly adopted into clinical practice due to the dramatic reductions in restenosis and repeat revascularizations associated with their use compared with bare-metal stents, Douglas explained. But reports of late stent thrombosis and higher mortality with DES, which resulted in the release of two special FDA advisories in 2006, led to much concern and a dip in their use. "We can now lay to rest concerns about the safety and effectiveness of these devices," Douglas told a press conference this morning.

"In over a quarter of a million patients in real-world practice, not the artificial setting of a randomized trial, we found a 25% reduction in death and a 25% reduction in heart attack in patients who received DES compared with bare-metal stents," she added to heartwire . "We saw no evidence of late stent thrombosis or of late excess heart attack or death in the DES patients. In clinical practice, these devices are safe. If you're a doctor, you can choose according to the patient characteristics without fear that you're going to do harm by implanting one of these. If you're a patient, you don't have to worry that there is some time bomb that--two or three years after angioplasty, when you're feeling good--there is going to be a sudden complication."

Douglas's trial was praised for its "unique" design, in which figures from the ACC National Cardiovascular Data Registry (NCDR) were linked with Medicare claims data to create a powerful resource allowing the long-term assessment of postmarketing stent performance in a community setting.

In discussion with heartwire , vice president of the ACC, Dr Ralph Brindis (Kaiser Permanente, San Francisco, CA), said: "What's so exciting is the number of patients. What we want to know as clinicians is how these things really play out in clinical practice in the real patients that we are taking care of. This novel approach . . . is brilliant because you have the opportunity to do longitudinal follow-up in a cost-effective manner and really get a flavor of outcomes." Brindis said the data reassured him about the safety of DES.

Discussant for the study, Dr Donald E Cutlip (Beth Israel Deaconess Medical Center, Boston, MA), said the study represents a rare opportunity to evaluate routine clinical practice outside the "limited generalizability of randomized clinical trials."

Survival Benefit Seen in All Subgroups

This novel approach . . . is brilliant.

In their observational study, Douglas and colleagues analyzed data from the ACC's NCDR on 262 700 patients over the age of 65 from 650 sites who had a stenting procedure performed from the beginning of 2004 to the end of 2006. Of these, 83% got a DES and the remainder a bare-metal stent. Because unique patient identifiers, such as names and Social Security numbers, are not permitted due to US patient-privacy laws, the registry figures were linked to Medicare claims using a probabilistic matching technique, which resulted in 76% of patients being correctly matched.

After adjustment for a total of 102 patient characteristics, DES patients had lower rates of death and MI, with minimal differences in revascularization, stroke, or bleeding at 30 months. The DES survival benefit was observed in all subgroups and persisted throughout the whole duration of follow-up.

Adjusted Results From Time-to-Event Analyses for Prespecified End Points

End point Adjusted hazard ratio* (95% CI)
Death 0.75 (0.72–0.79)
MI 0.77 (0.72–0.81)
Revascularization 0.91 (0.87–0.96)
Stroke 0.97 (0.88–1.07)
Bleeding 0.91 (0.84–1.00)
NSTEMI 0.79 (0.74–0.84)
STEMI 0.74 (0.67–0.82)
*Adjusted for inverse-probability–weighted covariates

Douglas said there were some limitations to the study. Although differences in baseline characteristics were rigorously adjusted for, "it is possible that the 'sicker' patients may have preferentially received a bare-metal stent in a way we were unable to adjust for despite our robust statistical models," she noted.

Stent Thrombosis Not Assessed Directly; No Data on Clopidogrel Use

We can now lay to rest concerns about the safety and effectiveness of these devices.

Also, the researchers could not directly assess rates of stent thrombosis, nor could they examine the impact of clopidogrel use: they had no drug information because they were using an administrative database. And patients in the study were enrolled before the FDA recommendation for prolonged clopidogrel use after implantation of a DES.

Douglas told heartwire : "The assumption is that some patients were taking clopidogrel. We have seen from our Duke experience that at the end of a year, 40% to 50% of our DES patients are taking clopidogrel. So some were, but many weren't. However, clopidogrel use is something we really just can't address with this data set."

Debate About Minimal Impact of DES on Revascularization

There was much debate after the presentation about the fact that DES are supposed to reduce revascularization and yet, in these results, there was only a minimal impact of DES on revascularization.

"You're absolutely right, these were unexpected findings," Douglas responded. "We did some additional thinking about that revascularization end point, and it was anytime a patient had an administrative billing charge for a cath lab intervention or cardiac surgery, so we have no way of knowing whether it was, for example, a staged procedure, whether it was a target lesion revascularization, target vessel revascularization, another de novo lesion, or something else. In our own data bank at Duke, target lesion revascularization is about half of what the overall revascularization rate is, so I think this is a different end point than what has been looked at in clinical trials."

Many people will walk away thinking that revascularization equals restenosis. . . . It's . . . hard to interpret.

One of the panelists for the session, Dr Richard J Shemin (Boston Medical Center, Boston, MA), said: "Many people will walk away thinking that revascularization equals restenosis, and that is clearly not what we are looking at here. In most other large registries and meta-analyses, there is generally about a 40% to 50% relative difference in target vessel revascularization with DES vs bare-metal stents [in favor of DES]. It's a very different end point--going back to the cath lab or having surgery--and it's a little bit confusing and hard to interpret."

Douglas agreed the end point was different and "extremely difficult to compare--it's apples and oranges compared with much of the rest of the literature." But, she said, from a patient perspective, "this may be a more important variable."

Unique Patient Identifiers Will Aid Outcomes Research

Brindis told heartwire that a rethink about patient-privacy laws in the US is of the utmost urgency. "The ACC has a very strong position paper on unique patient identifiers that we are pushing on an advocacy level to Congress, to make sure we have this ability to be able to track patients for safety and efficacy and clinical outcomes.

"If you ask patients, 'Would you like to know if your hip is okay over time, or your stent is safe?' they'll look at you and say, 'Aren't you doing that already?' and you say, 'No, we're not allowed, we don't have the ability to do that based on patient-privacy laws.' We need to make sure we're protecting patients and that people don't have access to data that they shouldn't and they don't misuse data, but we need to have a unique patient identifier.

"The model that [these researchers] came up with is brilliant, but it's not perfect," he added.

Asked during the question-and-answer session what she had learned about performing this kind of analysis, Douglas said: "You yield a very robust, very rich, huge data set that is very amenable to statistical analysis." But "it takes care and caution" to analyze it, she added. "Everything is statistically significant; it takes a really careful eye to talk about what's clinically significant and what isn't and very thoughtful risk adjustment."

Douglas reports no conflicts of interest. Disclosures for the coauthors are listed in the paper.


  1. Douglas PS, Brennan JM, Anstrom KJ et al. Clinical effectiveness of coronary stents in elderly persons. J Am Coll Cardiol 2009; DOI: 10.1016/j.jacc.2009.03.005. Available at:


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