Radiation therapy for coronary artery disease
When treating coronary artery disease with angioplasty or stents, an ongoing problem has been the high incidence of restenosis a recurrence of coronary artery blockage at the site of treatment. Patients who have developed restenosis in previously implanted stents soon will be presented with a new therapeutic option: coronary artery radiation, or brachytherapy.
For several years, researchers have postulated that restenosis might be prevented by applying small doses of radiation to the area of the coronary artery being treated. Last week the Food and Drug Administration approved the first coronary artery radiation system (the Beta-CathTM System from Novoste Corp.), and the approval of similar devices is expected soon. So far, coronary artery radiation is limited to restenosis occurring in stents.
How safe and effective is this intra-coronary radiation? Should it gain rapid, widespread acceptance? Or should it be regarded as an unproven treatment of last resort? In this article, we will try to answer these questions.
What causes restenosis after angioplasty or stenting?
Most restenosis is caused by thrombosis, or blood clotting, at the site of treatment. This type of restenosis can be partially prevented by using anti-clotting drugs.
But some restenosis is due to actual tissue growth at the site of treatment. It is likely that much of the restenosis that proves to be untreatable by repeat angioplasty may be due to this tissue growth restenosis. Such tissue growth a proliferation of the endothelial cells that normally line blood vessels cannot be prevented effectively with anticoagulants.
How does radiation therapy affect restenosis?
It has been known for decades that radiation can kill cells and prevent tissue growth. This, after all, is the mechanism by which radiation therapy can be effective in treating cancer.
So it makes perfect sense that radiation if it can be targeted accurately, and with appropriate doses might be able to treat the restenosis often seen after stent placement. Radiation therapy aimed at restenosis has two purposes: to treat the restenosis itself (by killing the cells that have re-occluded the stent), and to prevent further restenosis (by inhibiting tissue growth).
How is intra-coronary radiation administered?
Intra-coronary radiation is administered during a special heart catheterization procedure. The radiation itself is delivered by a new type of catheter designed to apply radiation to a localized area. The catheter is passed into the coronary arteries, and across the target area. (The target area is the area of restenosis that is to be treated.) Once the targeted area of stenosis is bracketed by the catheter, the radiation is applied.
Two varieties of radiation have been used so far gamma radiation and beta radiation. The first FDA-approved device uses beta radiation, but a gamma radiation device is expected to be approved within a few months.
Gamma radiation takes longer to apply it must be administered for approximately 20 minutes. While the gamma radiation is being delivered, medical personnel must leave the room to avoid exposure to stray radiation.
Beta radiation needs to be administered only for approximately 5 minutes, and because stray radiation levels are low, cath lab personnel do not need to leave the room.
Both kinds of radiation, however, are cumbersome to use, and require the presence of special equipment in the lab, the adoption of special precautionary procedures, and the presence of specially trained individuals, including a radiation oncologist. Investigators who have used intra-coronary radiation systems agree that a key to avoiding problems is the experience of the operator. These are complex procedures that require more than the standard expertise of the interventional cardiologist.
How well does intra-coronary radiation work?
Several randomized trials have now been reported on the effectiveness of intra-coronary radiation in humans, using various devices and various sources of radiation.
Most of these trials have shown a reduction in the rate of restenosis of approximately 30% to 50% following intra-coronary radiation. Further, these studies seem to show that patients who have an unusually high risk of restenosis in particular, diabetics seem to gain the most benefit from radiation therapy.
So in summary, while restenosis is not abolished by intra-coronary radiation, its incidence is significantly reduced.
What are the problems with intra-coronary radiation?
Several problems have been seen.
One problem has been the edge effect, the appearance of partial blockages of the coronary artery at either edge of the radiation field (the area treated with radiation.) This edge effect lesion, which takes on the appearance of a bar bell when visualized with an angiogram, is itself a form of restenosis, and represents a significant and difficult-to-treat adverse result. The cause of these edge effect lesions is controversial, but they are said to result when the radiation is inappropriately placed (the so-called geographic miss.)
Even more disturbing is the observation that patients who receive intra-coronary radiation appear to have an increased incidence of late coronary artery stenosis. Typical restenosis after angioplasty or stenting occurs within 6 months of the procedure. (This is the type of restenosis effectively treated by radiation.) But the late stenosis following intra-coronary radiation apparently can occur years after treatment. These late blockages can lead to myocardial infarctions (heart attacks) or death. (The reported incidence of late blockages following intra-coronary radiation has varied between 7% and 14%, but no truly long-term follow-up has been completed.)
The appearance of late stenosis has raised the specter of even more complications as time goes by. Radiation-induced coronary artery disease after radiation for cancer therapy, for instance, peaks at an average of 7 years after radiation. Some experts have speculated that the incidence of radiation-induced coronary artery blockage following intra-coronary radiation may take a similarly long time to become manifest. (The longest reported follow-up after intra-coronary radiation has been 3 years.)
Indeed, the FDA advisory panel, in its deliberation of available data on intra-coronary radiation devices, expressed similar concerns, and urged the long-term monitoring of patients receiving intra-coronary radiation.
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