Radiation of the arteries can reduce narrowingBMJ 2000; 320 doi: https://doi.org/10.1136/bmj.320.7232.402/c (Published 12 February 2000) Cite this as: BMJ 2000;320:402
Intracoronary artery radiation can significantly reduce restenosis rates after angioplasty, according to a new report (Circulation 2000;101:350-1,360-5).
Angioplasty is often complicated by restenosis, or coronary artery renarrowing. An estimated 30-50% of vessels dilated by angioplasty develop restenosis, a process that seriously limits the efficacy of the procedure. Restenosis can occur early or late after angioplasty and is heralded by symptoms of recurrent angina or even by myocardial infarct.
Restenosis is a consequence of the blood vessel wall responding to the “injury” of angioplasty and can thus be seen as a maladaptive repair response of the vessel wall to the injury induced by the coronary catheter.
Typically, the arterial wall responds via intimal proliferation, fibroblast invasion, and smooth muscle hyperplasia. The end result, a thickened arterial wall with scar formation, further compromises the vessel's luminal diameter.
Strategies for reducing restenosis rates have included mechanical stenting, antilipid drugs, and medication with platelet inhibitors, such as aspirin, ticlodipine, and glycoprotein IIa/IIIb inhibitors. Recently intracoronary radiation has been tried, but long term follow up studies are scanty.
The study published in Circulation was led by Dr Paul Teirstein of the Scripps Clinic in LaJolla, California. It enrolled 55 patients who had restenotic lesions after angioplasty into a double blind randomised trial that compared intracoronary radiation with iridium-192 pellets to placebo. Twenty six patients were randomised to the iridium group and 29 to the placebo group.
Efforts were made to control for age, sex, cholesterol level, history of hypertension, diabetes, previous heart attack, and location of the target lesion.
Inclusion criteria required a target lesion in a restenotic coronary artery that already contained a stent or was a candidate for stent placement. If a stent was not yet in place, stents were put in, and if stents were already in place, redilation with a balloon catheter was performed and additional stents were inserted, if necessary.
Patients then received either192Ir pellets or placebo pellets, which were left in place for 20–45 minutes to deliver an estimated radiation dosage of 800–3000 cGy to the adventitial border. Patients returned after six months and after three years for surveillance angiography.
Revascularisation via coronary artery bypass or by repeat angioplasty was done only if clinically indicated by recurrent symptoms or if cardiac testing showed ischaemia.
At the three year follow up, repeat medical histories were obtained. The researchers found that the patients treated with iridium had lower rates of target lesion revascularisation than the controls (15.4% v 48.4%;P<0.01.)
The restenosis rate for radiated patients having follow up coronary angiography was 33.3% compared with 63.6% for controls. This translated into a 74% reduction in target lesion revascularisation at six months and a 68% reduction at three years for the iridium group compared with the placebo group.
Thus the effectiveness of intracoronary brachytherapy was maintained at three years. The investigators also found that the rate of restenosis of non-target lesions was similar in both groups, showing some sort of internal control. Intracoronary artery radiation is presumed to work by inhibiting intimal proliferation and thereby disabling the cascade of events leading to restenosis. Although this study showed that such treatments can drastically reduce restenosis rates, many questions remain unanswered. For example, long term safety has yet to be assessed, and some concern remains about the possibility of radiation induced pericarditis and myocardial damage.
Also, radiation itself is considered a risk factor for the development of coronary artery disease—patients who undergo radiation therapy for breast cancer and lymphomas often have higher rates of early coronary artery disease than non-irradiated cohorts.
The Scripps study was also small, involving only 55 patients, and not well controlled for diabetes and previous stent placement. None the less, it does show a significant advance in the prevention of restenosis.