DENVER, CO — A drug-eluting balloon proved to be the match of a drug-eluting stent for treatment of any in-stent restenosis, offering the potential to spare patients from receiving yet another stent[1].
In a multicenter randomized trial, the balloon (SeQuent Please paclitaxel-eluting balloon, BBraun Melsungen, Germany) was demonstrated to be noninferior to the Xience everolimus-eluting stent at treating in-stent restenosis occurring in either DES or older, bare-metal stents.
Dr Jose PS Henriques
“The drug-eluting balloon appears to be an alternative therapy for any in-stent restenosis, negating the need for additional stenting,” said Dr Jose PS Henriques (Academic Medical Center, Amsterdam, the Netherlands) on behalf of colleagues in the Drug-Eluting Balloon for In-Stent Restenosis (DARE) trial.
The balloon is approved and has been in use in Europe for some time now but has not gotten the nod for coronary artery interventions from the US Food and Drug Administration. “I wish that our US FDA was listening, because we really would like to see this technology in the United States,” said Dr Roxana Mehran (Mount Sinai Medical Center, NY), who moderated a briefing where Henriques discussed the results prior to his presentation of the data here at TCT 2017.
“I feel that drug-coated balloons are important technologies for us to have in our armamentarium of treating in-stent restenosis,” Mehran said in an interview with theheart.org | Medscape Cardiology. “Putting in new layers of stent after stent, making club sandwiches out of our patients’ arteries, is not the best answer—we know that. Brachytherapy doesn’t work, and sending a patient for bypass surgery for a small vessel is not really the best possible therapy.”
DARE to Do Better
Back in the not-so-good old days of standalone balloon angioplasty, 6-month restenosis rates higher than 40% were seen in some studies. The advent of coronary artery stents in general and drug-eluting stents in particular has improved outcomes, but in-stent restenosis is still seen in anywhere from 3% to 20% of patients, Henriques said.
In the DARE trial, results of which are published online in JACC: Cardiovascular Interventions, investigators at eight sites throughout the Netherlands enrolled 278 patients with restenosis of either DES or bare-metal stent. The investigators defined restenosis as a greater than 50% diameter stenosis on visual assessment in-stent and/or <5 mm out of the stent. Patients with all types of restenosis lesions were eligible, including those with ostial, left main, bifurcation, chronic total occlusion, saphenous vein grafts, and arterial graft lesions.
Following pretreatment with dual antiplatelet therapy (aspirin and clopiodgrel, prasugrel [Effient, Lilly/Daiichi-Sankyo], or ticagrelor [Brilinta, AstraZeneca]), patients in each trial arm underwent predilation with the goal of full expansion of the previously implanted stent.
Patients who were assigned to the drug-eluting-balloon procedure had a balloon with the same diameter as the last predilation balloon. The balloon was inflated at a pressure of 6 to 8 atm for at least 30 seconds or, optimally, for 60 seconds. The protocol allowed for treatment of very long lesions with two or more drug-eluting balloons with a small overlap.
For patients randomized to the DES arm, investigators chose a stent size that could be deployed to the same diameter as the predilation balloon. The stent length was determined adding 2 to 3 mm to each end of the original stent’s length.
It took 5 years to accrue enough patients to reject the null hypothesis of inferiority with 80% power. The investigators eventually enrolled and randomized a total of 278 patients, 137 to the drug-eluting-balloon arm and 141 to the DES arm.
For the primary end point of 6-month in-segment minimal lumen diameter, 105 patients in the drug-eluting-balloon arm (77%) and 115 in the DES arm (82%) completed angiographic follow-up.
Baseline minimal lumen diameter was virtually identical in the two arms, at 0.78 mm in the drug-eluting-balloon arm, compared with 0.79 mm in the DES arm.
The postprocedural minimal lumen diameter favored the DES arm (1.72 mm vs 1.84 mm, P=0.005), but there was no difference in the primary end point at 6 months, with an in-segment minimal lumen diameter of 1.71 mm for drug-eluting-balloon vs 1.74 mm for DES (P=0.65).
In addition, in-segment late loss at 6-month angiographic follow-up was significantly less with the drug-eluting-balloon, at 0.17 mm vs 0.45 mm with the DES (P<0.001).
The point estimate of the difference in minimal lumen diameter between drug-eluting-balloon and DES was -0.03 mm, and the 95% lower confidence limit was -0.16, meeting the criterion for noninferiority (P<0.0001).
An analysis of the mean difference in 6-month minimal lumen diameter in major subgroups (in-stent restenosis stent type, diabetes status, sex, restenosis type, or reference vessel diameter) showed no significant differences.
Although the trial was not powered to detect clinical end points, an exploratory analysis found no significant differences between the arms in deaths, MI, strokes, target vessel revascularization, CABG, PCI interventions, or composite MACE.
Diminishing Returns
An interventional cardiologist who was not involved in the study told theheart.org | Medscape Cardiology that an effective alternative to stent-in-stent for treating restenosis would be welcome.
“When you have repeated episodes of restenosis, you can start with a vessel that’s 3 mm in diameter, and then when it restenoses and you place a second stent inside there, all of a sudden, even if you have a great stent result, you can be down to 2.5 mm, and then the next time you need to treat it for restenosis you’re down to a very tiny lumen, and that’s the problem with trying to treat in-stent restenosis with more stenting,” said Dr Cindy Grines (Hofstra/Northwell Medical Center, Hempstead, NY). Grines was an invited discussant at the briefing.
Dr David J Cohen (Saint Luke’s Health System, Kansas City, Missouri) also an invited discussant, echoed the comments of Mehran and Grines when he remarked that “this type of device obviously being similar in performance to drug-eluting stents would be a very, very welcome addition to our armamentarium, because one of the things we really don’t like to do as coronary interventionalists is to line up multiple stents inside of each other—that just becomes a self-perpetuating problem. So the ability to treat these patients reasonably well without needing more stents I think is tremendous advantage in the long run.”
The DARE trial was sponsored by the University of Amsterdam with support from BBraun Medical. Henriques disclosed an unrestricted research grant from BBraun. Disclosures for the coauthors are listed in the paper. Mehran discloses within the past 12 months she has had a financial interest/arrangement or affiliation with Abiomed, Abbott Vascular, CardioKinetix, Spectranetics, AstraZeneca, Bayer, Eli Lilly, Novartis, OrbusNeich, Medtronic, Bristol-Myers Squibb, Claret Medical, Janssen, Osprey Medical, the Medicines Company, Boston Scientific, Shanghai Braccosine, Elixer, and Medscape. Grines discloses within the past 12 months she has had a financial interest/arrangement or affiliation with Abbott Vascular and Volcano Corp. Cohen discloses within the past 12 months he has had a financial interest/arrangement or affiliation with Abbott Vascular, AstraZeneca, Boston Scientific, Edwards Lifesciences, Medtronic, Merck/Schering Plough, Corvia Medical, and Svelte Medical.
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