FUTURE II: Multicenter Evaluation of the Bioabsorbable Polymer-Based Everolimus-Eluting Stent
FUTURE II: Multicenter Evaluation of the Bioabsorbable Polymer-Based Everolimus-Eluting Stent
Presenter: Eberhard Grube, MD, Heart Center (Siegburg, Germany)
Everolimus is a novel macrolide immunosuppressant agent used to prevent autoimmune rejection after kidney, heart, and lung transplantation. It inhibits growth factor-stimulated cell proliferation by causing cell cycle arrest in the late G1 stage. Previous studies have shown that everolimus can inhibit proliferation of smooth muscle cells and clonal expansion of activated T cells.
The CHAMPION drug-eluting stent system (Guidant Corporation; Indianapolis, Indiana). incorporates everolimus into the bioabsorbable polymer matrix coating of the stent. The polymer coating is biocompatible in vivo, nonthrombogenic, and has high drug-loading capability with homogeneous drug-elution kinetics.
FUTURE I
The First Use To Underscore Reduction in Restenosis With Everolimus (FUTURE I) study (n = 42) was designed to assess the safety and performance of the everolimus-eluting stent. Patients with de novo lesions in vessels with a reference diameter of 2.75-4.0 mm and length ≤ 18 mm were included in the study. Patients with diabetes, recent myocardial infarction (MI) (occurring ≤ 4 weeks prior to randomization), low ejection fraction, and thrombus at the site of the lesion were excluded from enrollment. The primary endpoint of the study was the combined major adverse cardiac event (MACE) rate at 30 days. Key secondary endpoints included angiographic and intravascular ultrasound (IVUS) at 6 months for all patients and at 12-month follow-up for the drug-eluting stent arm.
According to the results presented at the European Society of Cardiology 2003 Congress, IVUS revealed that patients treated with the everolimus-eluting stent had a 0% binary restenosis rate, there were no cases of subacute stent thrombosis, and use of the stent was associated with an 87% angiographic reduction in in-stent late loss to 0.11 mm and an 87% reduction in neointimal volume. Furthermore, there were no cases of late stent malapposition.
FUTURE II: Study Design and Methods
FUTURE II was a prospective, randomized, multicenter study designed to assess the safety and efficacy of the everolimus-eluting stent (n = 21) compared with a bare-metal stent (n = 43). Inclusion and exclusion criteria were similar to those used in FUTURE I; however, FUTURE II included diabetic patients.
The primary endpoint of FUTURE II was angiographic late loss at 6 months. Secondary endpoints included MACE rate at 1 and 6 months and angiographic binary restenosis at 6-month follow-up.
FUTURE II: Results
Demographic and angiographic characteristics of FUTURE II patients were similar to those in the FUTURE I trial, but with the added inclusion of patients with diabetes (24% in the everolimus-eluting stent group and 28% in the control arm) (Table 1).
Table 1. FUTURE II: Baseline Clinical Characteristics
MI, myocardial infarction; PCI, percutaneous coronary intervention
The left anterior descending coronary artery was the most frequent target coronary artery in both groups, with a mean lesion length of 11 mm.
At 1-month follow-up, the outcomes were similar for the 2 groups, with a very low incidence of events. There were no cases of death or revascularization procedures. Clinical follow-up at 6 months showed similar outcomes for the 2 groups with regard to MACE rate, death, and target lesion revascularization (TLR) procedures (Figure). Similarly, at 12-month clinical follow-up, there was only 1 case of TLR in the everolimus-eluting stent group.
Figure. FUTURE II: clinical follow-up at 6 months.
At 6-month angiographic follow-up, use of the everolimus-eluting stent was associated with an 86% reduction in in-stent angiographic late loss and a 95% reduction in in-stent percent diameter stenosis. In addition, the everolimus-treated group reported an in-stent binary restenosis rate of 0% (Table 2).
Table 2. FUTURE II: 6-Month In-Stent Angiographic Follow-up
The results were similar when analyzing the whole segment ; however, there was also a significant reduction in binary restenosis (Table 3). There were no cases of late stent malapposition in either of the 2 groups.
Table 3. FUTURE II: 6-month Whole Segment Angiographic Follow-up
Conclusions
Investigators concluded that:
These are very preliminary data regarding a new player in the field of drug-eluting stents. FUTURE I had a very small number of patients and diabetics were excluded. FUTURE II also enrolled a small number of patients, but this time diabetic patients were included. Nevertheless, the results are promising, as we can see from the data. Late loss is a very useful index to assess the efficacy of drug-eluting stents, because it allows for comparisons between the different stents. Results of this comparison were very similar to those observed in the Sirolimus-Eluting Stent in De Novo Native Coronary Lesions (SIRIUS) trial using the sirolimus-eluting stent. Nevertheless, we will need a larger trial with more patients and more demanding lesions to assess the true potential of this new stent.
Presenter: Eberhard Grube, MD, Heart Center (Siegburg, Germany)
Everolimus is a novel macrolide immunosuppressant agent used to prevent autoimmune rejection after kidney, heart, and lung transplantation. It inhibits growth factor-stimulated cell proliferation by causing cell cycle arrest in the late G1 stage. Previous studies have shown that everolimus can inhibit proliferation of smooth muscle cells and clonal expansion of activated T cells.
The CHAMPION drug-eluting stent system (Guidant Corporation; Indianapolis, Indiana). incorporates everolimus into the bioabsorbable polymer matrix coating of the stent. The polymer coating is biocompatible in vivo, nonthrombogenic, and has high drug-loading capability with homogeneous drug-elution kinetics.
FUTURE I
The First Use To Underscore Reduction in Restenosis With Everolimus (FUTURE I) study (n = 42) was designed to assess the safety and performance of the everolimus-eluting stent. Patients with de novo lesions in vessels with a reference diameter of 2.75-4.0 mm and length ≤ 18 mm were included in the study. Patients with diabetes, recent myocardial infarction (MI) (occurring ≤ 4 weeks prior to randomization), low ejection fraction, and thrombus at the site of the lesion were excluded from enrollment. The primary endpoint of the study was the combined major adverse cardiac event (MACE) rate at 30 days. Key secondary endpoints included angiographic and intravascular ultrasound (IVUS) at 6 months for all patients and at 12-month follow-up for the drug-eluting stent arm.
According to the results presented at the European Society of Cardiology 2003 Congress, IVUS revealed that patients treated with the everolimus-eluting stent had a 0% binary restenosis rate, there were no cases of subacute stent thrombosis, and use of the stent was associated with an 87% angiographic reduction in in-stent late loss to 0.11 mm and an 87% reduction in neointimal volume. Furthermore, there were no cases of late stent malapposition.
FUTURE II: Study Design and Methods
FUTURE II was a prospective, randomized, multicenter study designed to assess the safety and efficacy of the everolimus-eluting stent (n = 21) compared with a bare-metal stent (n = 43). Inclusion and exclusion criteria were similar to those used in FUTURE I; however, FUTURE II included diabetic patients.
The primary endpoint of FUTURE II was angiographic late loss at 6 months. Secondary endpoints included MACE rate at 1 and 6 months and angiographic binary restenosis at 6-month follow-up.
FUTURE II: Results
Demographic and angiographic characteristics of FUTURE II patients were similar to those in the FUTURE I trial, but with the added inclusion of patients with diabetes (24% in the everolimus-eluting stent group and 28% in the control arm) (Table 1).
Table 1. FUTURE II: Baseline Clinical Characteristics
| Characteristic | Everolimus (n = 21) |
Control (n = 43) |
|---|---|---|
| Age (yrs) | 64 | 63 |
| Female (%) | 28 | 30 |
| Diabetes (%) | 24 | 28 |
| Hypertension (%) | 71 | 81 |
| Smoker (%) | 10 | 16 |
| Prior MI (%) | 19 | 19 |
| Previous PCI (%) | 33 | 44 |
The left anterior descending coronary artery was the most frequent target coronary artery in both groups, with a mean lesion length of 11 mm.
At 1-month follow-up, the outcomes were similar for the 2 groups, with a very low incidence of events. There were no cases of death or revascularization procedures. Clinical follow-up at 6 months showed similar outcomes for the 2 groups with regard to MACE rate, death, and target lesion revascularization (TLR) procedures (Figure). Similarly, at 12-month clinical follow-up, there was only 1 case of TLR in the everolimus-eluting stent group.
At 6-month angiographic follow-up, use of the everolimus-eluting stent was associated with an 86% reduction in in-stent angiographic late loss and a 95% reduction in in-stent percent diameter stenosis. In addition, the everolimus-treated group reported an in-stent binary restenosis rate of 0% (Table 2).
Table 2. FUTURE II: 6-Month In-Stent Angiographic Follow-up
|
|
Everolimus (n = 21) |
Control (n = 36) |
P |
| Minimal lumen diameter (mm) | 2.74 | 2.02 | < .0001 |
| Percent diameter stenosis (%) | 2.94 | 30.4 | < .0001 |
| Binary restenosis (%) | 0 | 19.4 | NS |
| Late loss (mm) | 0.12 | 0.85 | < .0001 |
The results were similar when analyzing the whole segment ; however, there was also a significant reduction in binary restenosis (Table 3). There were no cases of late stent malapposition in either of the 2 groups.
Table 3. FUTURE II: 6-month Whole Segment Angiographic Follow-up
|
|
Everolimus (n = 21) |
Control (n = 36) |
P |
|---|---|---|---|
| Minimal lumen diameter (mm) | 2.19 | 1.75 | .003 |
| Diameter stenosis (%) | 22.4 | 40.3 | .0006 |
| Binary restenosis (%) | 4.8 | 30.6 | .04 |
| Late loss (mm) | 0.17 | 0.54 | .002 |
Investigators concluded that:
Everolimus-coated stents are very effective in reducing neointimal proliferation at 6 months.
There were no cases of subacute or late stent thrombosis.
There were no cases of late stent malapposition.
The safety and efficacy of the stent are sustained at 12 months.
These are very preliminary data regarding a new player in the field of drug-eluting stents. FUTURE I had a very small number of patients and diabetics were excluded. FUTURE II also enrolled a small number of patients, but this time diabetic patients were included. Nevertheless, the results are promising, as we can see from the data. Late loss is a very useful index to assess the efficacy of drug-eluting stents, because it allows for comparisons between the different stents. Results of this comparison were very similar to those observed in the Sirolimus-Eluting Stent in De Novo Native Coronary Lesions (SIRIUS) trial using the sirolimus-eluting stent. Nevertheless, we will need a larger trial with more patients and more demanding lesions to assess the true potential of this new stent.
