PES Show Delayed Healing in STEMI Patients, Clinical Significance Downplayed

In patients with ST-segment elevation myocardial infarction (STEMI), paclitaxel-eluting stents (PES) show more incomplete strut coverage than bare-metal stents (BMS), a hallmark of delayed endothelialization thought to raise the risk of late stent thrombosis. Results of the optical coherence tomography (OCT) substudy of the HORIZONS-AMI trial were published online January 10, 2011, ahead of print in Circulation.

But the clinical relevance of these differences may not be meaningful, several researchers said.

The randomized, multicenter HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial compared bivalirudin with heparin plus a glycoprotein IIb/IIIa inhibitor in 3,602 STEMI patients. Of these patients, 3,000 were eligible for randomization in a 3:1 ratio to either PES (n = 2,257) or BMS (n = 749).

In the new substudy, researchers led by Giulio Guagliumi, MD, of Ospedali Riuniti di Bergamo (Bergamo, Italy), used OCT to analyze a total of 44,139 stent struts from 118 consecutive randomized patients at their institution from the stenting arm of the trial (89 PES; 29 BMS). Dual antiplatelet therapy maintenance was high and equivalent between the PES and BMS groups (89.9% and 86.2%, respectively; P = 0.73).

At 13-month follow-up, the percentage of uncovered struts per lesion (primary endpoint) was higher with PES than BMS, as were several other OCT endpoints, including length of segments with uncovered struts, length of malapposition, and prevalence of malapposed struts per lesion (table 1).

Table 1. OCT Analysis at 13 Months

In addition, at least 1 malapposed strut was present in 46.1% of the PES group compared with 10.3% of the BMS group (P = 0.0006).

Still, percentage net volume obstruction was far less in the PES group (19.2 ± 11.3% vs. 36.0 ± 15.4%; P < 0.0001), and the frequency of abnormal intra-stent tissue, the term used to describe any masses protruding through the struts into the lumen, was equivalent between the PES and BMS groups (24.7% vs. 21.9%; P = 0.74).

“The present study has clearly demonstrated that at 13 months after implantation in STEMI, PES compared to BMS [are] more likely to have a greater number and larger spatial distribution of uncovered and malapposed stent struts,” the authors conclude. “The major issue regards the clinical relevance of this finding.”

Different Story from Autopsy Studies

The investigators note that previous research implicated the impaired endothelialization of DES stent struts as a factor in delayed stent thrombosis in STEMI patients. However, the reduced restenosis that occurs with PES vs. BMS may reduce secondary thrombotic events, they point out.

In a telephone interview with TCTMD, study coauthor Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), called the link between uncovered struts and late stent thrombosis, “very debatable.”

He noted that autopsy studies have shown uncovered struts in STEMI patients with DES ranging from 40% to 50%, compared with extremely few uncovered struts in BMS cases.

“But we’re not seeing that here,” Dr. Stone said referring to the current study results. “We clearly do see biological differences in the vascular responses to the 2 different [stent] drug types with somewhat greater malapposition and less extensive strut coverage with paclitaxel stents compared with bare metal, but the differences are relatively small. It’s not like 99% coverage vs. 50% coverage; it’s 99% vs. 94%, and there were no differences in intra-stent thrombus or other material.”

Long-term HORIZONS-AMI Results Lend Clarity

David E. Kandzari, MD, of Piedmont Heart Institute (Atlanta, GA), focused on the bigger picture. “The issue here is that despite the statistical significance, are these findings clinically meaningful?” he told TCTMD in a telephone interview. “This is especially sensitive because of the persistent debate over the use of DES in AMI, and the ongoing debate about healing and mechanistic findings vs. true clinical outcomes.”

Both Drs. Stone and Kandzari agreed that all clinicians need to do is look to the long-term results of the main HORIZONS-AMI trial to determine the clinical impact of the current study results. In the stent arm of the trial, patients receiving PES experienced a 40% reduction in ischemic TLR compared with BMS patients (9.4% vs. 15.1%; P < 0.001) at 3 years, while rates of all-cause mortality, cardiac mortality, reinfarction, stroke, and stent thrombosis were equivalent. The results were reported in September 2010 at the annual Transcatheter Cardiovascular Therapeutics symposium in Washington, DC.

“Those who choose the side of the debate against DES will continue to reference data from the current study as supportive of other pathological and autopsy data supporting impaired healing,” Dr. Kandzari said, “and those who use DES will go back to what is most meaningful, and that is how patients have actually done in this trial. What [detractors] cannot say is that patients have done worse over time as a trial population with DES, and in fact, from an efficacy standpoint, they do better.”

OCT Has Its Own Issues

Dr. Stone pointed out that while the resolution of OCT is greater than IVUS, the newer technology still has important limitations. “You can determine on a strut-by-strut basis whether or not there’s tissue coverage, but even OCT doesn’t have the resolution to see just one endothelial cell,” he said. “It doesn’t have the resolution to see what type of tissue is covering the stent, so you may have just fibrin covering the stent as opposed to healthy endothelial cells. OCT can’t tell the difference.”

Even if endothelial cells are present, Dr. Stone added, OCT cannot determine if they are actually functional.

“In part, this manuscript represents the enthusiasm to report findings from a novel and unique technology and the struggle to make it conform to the clinical observations, which might be disparate from the OCT findings,” Dr. Kandzari said. “In other words, you find these differences that are statistically significant, and perhaps there’s an interest in making them sensational, but at the same time when we look at how the patients have done, they’ve done very well and in some regards better with DES.”

He added that sensitivity to the polymer has also been linked to the development of late stent thrombosis from DES. “So whether these issues contribute to the possibility of stent thrombosis has to be considered at least with equal weight to the possibility of having ‘so-called’ uncovered stent struts,” Dr. Kandzari said.

Note: Dr. Stone and several other coauthors of the subanalysis are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 

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Source:
Guagliumi G, Costa MA, Sirbu V, et al. Strut coverage and late malapposition with paclitaxel-eluting stents compared with bare metal stents in acute myocardial infarction: Optical coherence tomography substudy of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. Circulation. 2010;Epub ahead of print.

 

 

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