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In patients undergoing primary percutaneous coronary intervention (PCI), use of a drug-eluting balloon (DEB) followed by implantation of a bare-metal stent (BMS) appears to be no more effective at preventing restenosis than a BMS alone, according to a study published online April 11, 2012, ahead of print in the Journal of the American College of Cardiology.

Findings from the DEB-AMI (Drug Eluting Balloon in Acute ST-Segment Elevation Myocardial Infarction) trial were originally presented in November 2011 at the annual Transcatheter Cardiovascular Therapeutics scientific symposium in San Francisco, CA.

Investigators led by Pieter R. Stella, MD, PhD, of University Medical Center Utrecht (Utrecht, The Netherlands), randomized STEMI patients at 2 centers to primary PCI with a BMS (Genius Magic; Eurocor, Bonn, Germany; n = 51), a paclitaxel-eluting balloon (DEB; Dior, Eurocor) followed by the same BMS (n = 50), or a paclitaxel-eluting stent (PES; Taxus Liberté, Boston Scientific, Natick, MA; n = 49). Before primary PCI, all patients had undergone successful thrombus aspiration.

The DEB features a coating of 3 µg of paclitaxel mixed with a shellac carrier to preclude wash-off of the drug during catheter manipulation. The 3 treatment arms were well balanced for all variables. Angiographic success was about 98% and procedural success at least 96% in each group.

Angiographic Outcomes Disappoint

Six-month angiographic follow-up, available in about 85% of all groups, showed that the primary endpoint of in-stent late luminal loss was similar for the DEB and BMS groups, and both results were inferior to that of the PES group. The same pattern was seen for in-stent binary restenosis (table 1).

Table 1. Six-Month Angiographic Outcomes

At the same time point, there were no differences between the BMS and DEB groups in rates of MACE (death, MI, and TVR) or TLR, but both outcomes were higher than those for the PES group. Incidences of cardiac death and Academic Research Consortium-defined stent thrombosis were low and similar for all 3 groups (table 2).

Table 2. Six-Month Clinical Outcomes

^a Two cases of Academic Research Consortium-defined definite stent thrombosis.

During angiographic follow-up, 27 patients randomized from the 3 groups also underwent evaluation with optical coherence tomography (OCT). Vessel size and stent length were similar among the groups. The average percentage of uncovered and malapposed stent struts per lesion ranged from 0 for the BMS group to 2.84% for the DEB group and 5.21% for the PES group (overall P < 0.01). Similarly, neointimal volume was reduced in the DEB group compared with the BMS group (60.0 mm³ vs. 101.3 mm³; P = 0.04) but was increased compared with the PES group (24.2 mm³; P = 0.01 for DEB vs. PES).

In addition, 21 patients were tested for endothelial function via angiographic change in minimum lumen diameter after infusion of different concentrations of acetylcholine. Virtually no effect was seen in the BMS group, with substantial stability of the vascular dimensions. By contrast, both DEB and PES showed paradoxical vasoconstriction related to the incremental doses of acetylcholine.

The authors observed that although the OCT results suggest that DEB drug release did inhibit neointimal proliferation, the effect was insufficient to reduce late luminal loss compared with BMS alone. Moreover, the delayed healing with DEB may contribute to increased risk of stent thrombosis.

Drug Carrier, Inconsistent Predilation May Account for Failure

There are several possible explanations for the findings, the authors say:

• In this DEB, insufficient paclitaxel may be delivered to the lesion site, perhaps due to the shellac excipient used. Experimental models have shown that the degree of late luminal loss depends in part on the release properties of the drug carrier.
• Only 60% of patients in the DEB group underwent predilation with a regular balloon, which is thought to improve drug uptake by creating tiny dissections in the vessel wall.
• In the presence of calcified lesions, predilation may facilitate lesion crossing and thereby minimize loss of the drug as the balloon passes through.

In a separate small but suggestive analysis, the 25 DEB patients who received predilation had less late luminal loss than the 17 who did not (0.49± 0.52 mm vs. 0.85 ± 0.56 mm; P = 0.04).

Dr. Stella and colleagues conclude that “the OCT outcomes with a reduction in neointimal hyperplasia in the DEB group seem to suggest that the changes induced by DEB might indeed have clinical significance when applied to an appropriate number of patients. Hence, future larger randomized studies should be performed to put the current findings into perspective.”

Setback Does Not Spell Dream’s End

“This is an early negative study, but it’s way too early to get too down [regarding DEB’s prospects] over one paper,” Robert S. Schwartz, MD, of the Minneapolis Heart Institute (Minneapolis, MN), told TCTMD in a telephone interview.

There are a growing number of DEB technologies with different excipients and different drug release characteristics, and this one simply may not have been the best for this application, Dr. Schwartz said. Also, “we are in deep water” in the STEMI environment with disrupted plaque and inflammation contributing to the unknowns, he commented. In fact, since there is limited experience with DEBs in the coronary bed, “I think we should start with simple lesions,” he added.

The OCT results are interesting from a physiological standpoint, Dr. Schwartz noted, but they are several levels removed from clinical outcomes, which should lead the way. “When we understand what’s happening clinically, then we can try to understand what these images mean,” he said.

This setback is far from derailing the DEB “dream of having our cake and eating it too by having the drug do its job of preventing restenosis and then go away quickly so clopidogrel can be stopped after 1 month,” Dr. Schwartz said.

Study Details

The minimal inflation time for the drug-eluting balloon is 30 seconds (45 to 60 seconds is recommended) to allow sufficient drug release into the vessel wall to prevent smooth muscle proliferation.

 

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Source:
Belkacemi A, Agostoni P, Nathoe HM, et al. First results of the DEB-AMI (Drug Eluting Balloon in Acute ST-Segment Elevation Myocardial Infarction) trial: A multicenter randomized comparison of drug-eluting balloon plus bare-metal stent versus bare-metal stent versus drug-eluting stent in primary percutaneous coronary intervention with 6-month angiographic, intravascular, functional, and clinical outcomes. J Am Coll Cardiol. 2012;Epub ahead of print.

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