Intracoronary Radiation to Prevent Recurrence of In-stent Restenosis in Diabetic Patients: 6-Month R
Intracoronary Radiation to Prevent Recurrence of In-stent Restenosis in Diabetic Patients: 6-Month Results
Presenter: M. Sabaté Tenas, MD (Madrid, Spain)
Patients with diabetes mellitus referred for percutaneous coronary intervention (PCI) represent one of the greatest challenges for the interventional cardiologist. These patients tend to be older and sicker, presenting with more frequent comorbid conditions such as hypertension, hyperlipidemia, and more advanced cardiovascular disease, as manifested by multivessel coronary artery disease and congestive heart failure. Restenosis continues to be the major limitation of PCI, particularly in diabetic patients. Restenosis rates after balloon angioplasty in diabetic patients can be very high (up to 63%), and although stenting has been shown to decrease these rates, diabetic patients continue to have significantly higher restenosis rates and a greater incidence of clinical events following PCI. Intracoronary radiation therapy has proven to be an effective treatment alternative for the prevention of the recurrence of in-stent restenosis, especially in diabetic patients. The use of prophylactic intracoronary brachytherapy remains controversial.
Aim and Design
This single-center, prospective, randomized, placebo-controlled study was conducted to assess the efficacy and effectiveness of intracoronary beta radiation using a P source following successful coronary stent implantation in diabetic patients with de novo coronary stenosis. Inclusion criteria called for diabetic patients with a lesion in a native coronary vessel (measuring 2.3 to 4.0 mm) and injury lengths ≤ 45 mm.
Primary Endpoints:
Secondary Endpoints:
A total of 92 patients underwent randomization (46 placebo and 46 radiation). Clinical follow-up was available for all patients and angiographic follow-up was available in 93% and 91% of patients randomized to the placebo and treatment arms, respectively. IVUS analysis was also available in 93.4% and 91.3% of control and treated patients, respectively. Baseline characteristics of the patients were similar (Table).
Table. Baseline Clinical Characteristics
Baseline angiographic parameters were also similar between the 2 groups, with a reference vessel diameter of 2.75 mm and lesion length of 12-13 mm. Procedural success was achieved in all patients. In-hospital outcomes were good; only 1 noncardiac death and 1 non-Q-wave myocardial infarction (MI) in the radiation group were reported. The primary endpoint, mean in-stent neointimal hyperplasia, was significantly lower in the radiation arm, with a 52% reduction (Figure 1).
Figure 1. Mean in-stent neointimal hyperplasia.
Restenosis rates by segments were lower inside the stent, as well as in the injured area, in the radiated zone, and in the analyzed area (Figure 2). At 6 months, clinical outcomes were similar between the 2 groups, with the exception of a higher rate of MI in the radiation arm, which investigators attribute to the premature discontinuation of clopidogrel (Figure 3).
Figure 2. Quantitative coronary angiography: restenosis rate by segment.
Figure 3. Clinical outcomes at 6-month follow-up.
Conclusions
On the basis of their findings, investigators concluded that intracoronary brachytherapy significantly inhibited in-stent neointimal hyperplasia after stent implantation in diabetic patients. However, this did not translate to any clinical benefit at 1 year because of the edge effect and late stent thrombosis, as well as the fact that patients were not maintained on long-term clopidogrel therapy. Thus, the present study does not support the routine use of prophylactic intracoronary radiation in this high-risk group of diabetic patients.
Comments
Despite the small sample size, this study has shown disappointing clinical outcomes for diabetic patients treated with intracoronary radiation as a prophylactic treatment for the prevention of in-stent restenosis. Clearly, in the era of drug-eluting stents, intracoronary radiation seems out of context. Perhaps the therapy should be reserved for its original indication: the prevention of the recurrence of in-stent restenosis. Or possibly, it should be performed after the implantation of a drug-eluting stent.
Reference
Presenter: M. Sabaté Tenas, MD (Madrid, Spain)
Patients with diabetes mellitus referred for percutaneous coronary intervention (PCI) represent one of the greatest challenges for the interventional cardiologist. These patients tend to be older and sicker, presenting with more frequent comorbid conditions such as hypertension, hyperlipidemia, and more advanced cardiovascular disease, as manifested by multivessel coronary artery disease and congestive heart failure. Restenosis continues to be the major limitation of PCI, particularly in diabetic patients. Restenosis rates after balloon angioplasty in diabetic patients can be very high (up to 63%), and although stenting has been shown to decrease these rates, diabetic patients continue to have significantly higher restenosis rates and a greater incidence of clinical events following PCI. Intracoronary radiation therapy has proven to be an effective treatment alternative for the prevention of the recurrence of in-stent restenosis, especially in diabetic patients. The use of prophylactic intracoronary brachytherapy remains controversial.
Aim and Design
This single-center, prospective, randomized, placebo-controlled study was conducted to assess the efficacy and effectiveness of intracoronary beta radiation using a P source following successful coronary stent implantation in diabetic patients with de novo coronary stenosis. Inclusion criteria called for diabetic patients with a lesion in a native coronary vessel (measuring 2.3 to 4.0 mm) and injury lengths ≤ 45 mm.
Primary Endpoints:
In-stent mean neointimal area as assessed by intravascular ultrasound (IVUS) at 6-month angiographic follow-up (primary endpoint of effectiveness)
Minimal lumen area of the entire vessel segment as assessed by IVUS at 6-month angiographic follow-up (primary endpoint of clinical efficacy)
Secondary Endpoints:
Angiographic parameters as assessed by quantitative coronary angiography at 6-month angiographic follow-up
Major adverse cardiac events at 30 days and at 6, 7,12, and 13 months.
Development of complications (eg, aneurysm, edge effect, thrombosis)
A total of 92 patients underwent randomization (46 placebo and 46 radiation). Clinical follow-up was available for all patients and angiographic follow-up was available in 93% and 91% of patients randomized to the placebo and treatment arms, respectively. IVUS analysis was also available in 93.4% and 91.3% of control and treated patients, respectively. Baseline characteristics of the patients were similar (Table).
Table. Baseline Clinical Characteristics
| Characteristic | Placebo (n = 46) |
Radiation (n = 46) |
|---|---|---|
| Age (yrs) | 64 | 66 |
| Male gender (%) | 69 | 67 |
| Insulin treated (%) | 35 | 35 |
| Non-insulin treated (%) | 65 | 65 |
| Hypertension (%) | 52 | 54 |
| Hyperlipidemia (%) | 35 | 35 |
| Prior MI (%) | 46 | 41 |
| Multivessel disease (%) | 53 | 52 |
| MI, myocardial infarction |
Baseline angiographic parameters were also similar between the 2 groups, with a reference vessel diameter of 2.75 mm and lesion length of 12-13 mm. Procedural success was achieved in all patients. In-hospital outcomes were good; only 1 noncardiac death and 1 non-Q-wave myocardial infarction (MI) in the radiation group were reported. The primary endpoint, mean in-stent neointimal hyperplasia, was significantly lower in the radiation arm, with a 52% reduction (Figure 1).
Restenosis rates by segments were lower inside the stent, as well as in the injured area, in the radiated zone, and in the analyzed area (Figure 2). At 6 months, clinical outcomes were similar between the 2 groups, with the exception of a higher rate of MI in the radiation arm, which investigators attribute to the premature discontinuation of clopidogrel (Figure 3).
On the basis of their findings, investigators concluded that intracoronary brachytherapy significantly inhibited in-stent neointimal hyperplasia after stent implantation in diabetic patients. However, this did not translate to any clinical benefit at 1 year because of the edge effect and late stent thrombosis, as well as the fact that patients were not maintained on long-term clopidogrel therapy. Thus, the present study does not support the routine use of prophylactic intracoronary radiation in this high-risk group of diabetic patients.
Comments
Despite the small sample size, this study has shown disappointing clinical outcomes for diabetic patients treated with intracoronary radiation as a prophylactic treatment for the prevention of in-stent restenosis. Clearly, in the era of drug-eluting stents, intracoronary radiation seems out of context. Perhaps the therapy should be reserved for its original indication: the prevention of the recurrence of in-stent restenosis. Or possibly, it should be performed after the implantation of a drug-eluting stent.
Reference
Gruberg L, Waksman R, Ajani AE, et al. The effect of intracoronary radiation for the treatment of recurrent in-stent restenosis in patients with diabetes mellitus. J Am Coll Cardiol. 2002;39:1930-1936.