Washington, DC - Despite the initial efficacy of vascular brachytherapy in reducing in-stent restenosis, five-year follow-up from the Gamma-1 study has shown disappointing results. At five years, investigators report declining efficacy for intracoronary radiation, showing there were no statistically significant differences in MACE, TLR, or TVR rates between the irradiated group and the control group.
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Dr Martin Leon |
"What we have learned in the subsequent five years is that there has been an attrition in the benefit such that by five years, if you do a statistical analysis of two groups for every clinical parameter we assessedTLR, TVR, target vessel failure, and MACEthe two therapies are statistically equivalent and in most cases superimposable," said Dr Martin Leon (Columbia University Medical Center, New York) during a press conference at the TCT 2004meeting. "The incremental benefit that was demonstrated in the early phase has been diminished with a threefold higher late-TLR rate in the vascular brachytherapy patients."
Five-year follow-up
The Gamma-1 study was a blinded, randomized, controlled trial with 252 patients comparing angiographic and clinical outcomes after Ir-192 vascular brachytherapy vs placebo for in-stent restenosis in native coronary lesions. The primary end point of the study was nine-month MACEa composite of death, MI, and TLRand annual clinical follow-up at one to five years.
At nine months, MACE and TLR were significantly reduced, from 44.6% and 42.1%, respectively, to 29.0% and 25.2%. However, after five years, there was a progressive decline in vascular brachytherapy efficacy.
GAMMA-1: Five-year follow-up
End point |
Ir-192 (n=131) |
Control group (n=121) |
p |
MACE (%) |
48.9 | 54.5 | 0.380 |
Death (%) |
9.9 | 9.9 | 1.000 |
MI (%) |
17.6 | 9.1 | 0.064 |
TLR (%) |
40.5 | 47.9 | 0.254 |
Investigators also found that compared with placebo, vascular brachytherapy induced an approximately threefold higher frequency of late TLR events, most occurring during the first three years.
"What this means is that this therapy, initially aborting the restenosis process, has only delayed the process," said Leon. "By five years there is no longer any benefit."
During a press conference to present these results, Leon said the results are a sober reminder that beneficial short-term therapies may not have lasting efficacy. However, he said, that while they are aware of the importance of long-term data, the absolute stability of drug-eluting-stent data is encouraging. TAXUS II and TAXUS IV data, presented at TCT this week and reported by heartwire, were positive, as were four-year data from RAVEL and SIRIUS.
"We view vascular brachytherapy as if you're basically exploding a bomb in the coronary arteries," said Leon. "You eternally alter the biology of the vessel wall, you affect endothelialization, you affect platelet absorption, which requires extended dual antiplatelet therapy, and you affect the healing response."
"We view DES not as a bomb, but more as a laser beam," continued Leon. "We think that the effects are shorter, more specific, and we're hopeful that the effects will be much more durable."
Leon said that in the past year, he has performed vascular brachytherapy for the treatment of in-stent restenosis only twice, both times in patients without other options. "We have essentially ceased using vascular brachytherapy," he said.
Results were expected
Commenting on the five-year results for heartwire, Dr Gary Mintz (Cardiovascular Research Foundation, New York) said many clinicians expected these results and that for all practical purposes the use of vascular brachytherapy has dwindled substantially.
"We got the hint that these results were coming," said Mintz. "This is not the first time we've seen late catch-up. I think if you've been looking at this field critically, and not just the one-year data, but the three-year data began to hint that the curves were converging. Still, it is slightly surprising that the curves are no longer statistically significant."