ENDEAVOR I: Multicenter Evaluation of ABT-578 Elution From a Phosphorylcholine-Coated Stent --
ENDEAVOR I: Multicenter Evaluation of ABT-578 Elution From a Phosphorylcholine-Coated Stent -- 4-month Angiographic and IVUS Follow-up
Presenter: Ian T. Meredith, MD, Medical Centre (Melbourne, Australia)
There is no doubt that the new generation of drug-eluting stents is changing the outlook for interventional cardiology. Already approved by the US Food and Drug Administration, the sirolimus-eluting Cypher stent (Cordis Corporation, Miami Lakes, Florida), has established the benchmark for all other drug-eluting stent platforms. In addition to sirolimus, paclitaxel has also made a name for itself as an effective compound for drug-eluting stents. Now, however, other "second-generation" drug-eluting stent platforms are under development that use alternative agents for the prevention of restenosis. Investigators hope that new agents can meet -- and possibly exceed -- the benefits of the earlier platforms.
ABT-578 is one of the new compounds under investigation. ABT-578 is a rapamycin-like agent that binds the FKBP12 protein. This complex blocks the mTOR signal transduction, and in this way provides its antiproliferative action.
ABT-578 is used as the antiproliferative agent in the Endeavor drug-eluting stent (Medtronic AVE; Minneapolis, Minnesota). The drug is released from a phosphorylcholine (PC) polymer that is coated on the Driver cobalt alloy stent. The drug is mainly localized on the arterial wall of the stent with a PC coating and carries 10 mcg of ABT-578 per millimeter of stent length.
Study Design and Methods
The phase 1 ENDEAVOR I study is designed to assess the safety and effectiveness of the ABT-578-coated Driver stent in 100 patients with single de novo lesions in native coronary arteries.
The study's primary endpoint was major adverse cardiac events (MACE) rate and late loss at 4 months by quantitative coronary angiography (QCA). Secondary endpoints included:
Patients with single de novo lesions measuring 3.0-3.5 mm in diameter and < 15 mm in length and diameter stenosis ≥ 50% and ≤ 100% were included in the study. Patients were treated with antiplatelet therapy for 3 months following the procedure.
Exclusion criteria included patients with:
The target lesion in the majority of patients was the left anterior descending coronary artery (42%), and the right coronary artery was the target lesion in35% of patients. Investigators reported a 100% success rate for all procedures, including device deployment. In addition, 4-month clinical, angiographic, and IVUS follow-up were available in ≥ 98% of patients. Baseline clinical characteristics of patients were similar to those of other drug-eluting stent study populations (Table 1).
Table 1. ENDEAVOR I: Baseline Clinical Characteristics
MI, myocardial infarction; PCI, percutaneous coronary intervention
There were very few MACE events at 30 days and at 4 months; only 1 TLR was reported at 4 months (Table 2).
Table 2. ENDEAVOR I: Clinical Outcomes at 30 Days and at 4 Months
MACE, major adverse cardiac event; MI, myocardial infarction; TLR, target lesion revascularization
QCA results at 4-month follow-up were also good, with low rates of late loss at the stented site and in all of the segments (Table 3). IVUS analysis found no incidence of late acquired incomplete apposition and an increase in external elastic membrane volume at 4 months (Table 4).
Table 3. ENDEAVOR I: QCA Results
MLD, minimal lumen diameter; QCA, quantitative coronary angiography
Table 4. ENDEAVOR I: IVUS Results
EEM, external elastic membrane
Conclusions
Investigators concluded that:
This is a very important step toward the incorporation of a new drug-eluting stent into this very exclusive club. We need to take into account that this was not a randomized study and it was done in very simple lesions. Nevertheless, these preliminary results are very promising, and the real proof will come from the pending ENDEAVOR II trial, which will randomize patients to either the bare-metal Driver stent or the ABT-578-coated Endeavor stent.
Presenter: Ian T. Meredith, MD, Medical Centre (Melbourne, Australia)
There is no doubt that the new generation of drug-eluting stents is changing the outlook for interventional cardiology. Already approved by the US Food and Drug Administration, the sirolimus-eluting Cypher stent (Cordis Corporation, Miami Lakes, Florida), has established the benchmark for all other drug-eluting stent platforms. In addition to sirolimus, paclitaxel has also made a name for itself as an effective compound for drug-eluting stents. Now, however, other "second-generation" drug-eluting stent platforms are under development that use alternative agents for the prevention of restenosis. Investigators hope that new agents can meet -- and possibly exceed -- the benefits of the earlier platforms.
ABT-578 is one of the new compounds under investigation. ABT-578 is a rapamycin-like agent that binds the FKBP12 protein. This complex blocks the mTOR signal transduction, and in this way provides its antiproliferative action.
ABT-578 is used as the antiproliferative agent in the Endeavor drug-eluting stent (Medtronic AVE; Minneapolis, Minnesota). The drug is released from a phosphorylcholine (PC) polymer that is coated on the Driver cobalt alloy stent. The drug is mainly localized on the arterial wall of the stent with a PC coating and carries 10 mcg of ABT-578 per millimeter of stent length.
Study Design and Methods
The phase 1 ENDEAVOR I study is designed to assess the safety and effectiveness of the ABT-578-coated Driver stent in 100 patients with single de novo lesions in native coronary arteries.
The study's primary endpoint was major adverse cardiac events (MACE) rate and late loss at 4 months by quantitative coronary angiography (QCA). Secondary endpoints included:
Target vessel failure and target lesion revascularization (TLR) at 9 months
Late loss at 12 months
Intravascular ultrasound (IVUS) at 4 and 12 months.
Patients with single de novo lesions measuring 3.0-3.5 mm in diameter and < 15 mm in length and diameter stenosis ≥ 50% and ≤ 100% were included in the study. Patients were treated with antiplatelet therapy for 3 months following the procedure.
Exclusion criteria included patients with:
Congestive heart failure, renal insufficiency
Acute myocardial infarction within 72 hours
Any percutaneous coronary intervention (past or planned) within 30 days of enrollment
Evidence of thrombus in target vessel
The target lesion in the majority of patients was the left anterior descending coronary artery (42%), and the right coronary artery was the target lesion in35% of patients. Investigators reported a 100% success rate for all procedures, including device deployment. In addition, 4-month clinical, angiographic, and IVUS follow-up were available in ≥ 98% of patients. Baseline clinical characteristics of patients were similar to those of other drug-eluting stent study populations (Table 1).
Table 1. ENDEAVOR I: Baseline Clinical Characteristics
| Characteristic | N = 100 |
|---|---|
| Age (yrs) | 59 |
| Female (%) | 21 |
| Diabetes (%) | 16 |
| Hyperlipidemia (%) | 92 |
| Smoker (%) | 34 |
| Prior MI (%) | 47 |
| Previous PCI (%) | 19 |
| Unstable angina (%) | 39 |
There were very few MACE events at 30 days and at 4 months; only 1 TLR was reported at 4 months (Table 2).
Table 2. ENDEAVOR I: Clinical Outcomes at 30 Days and at 4 Months
| Endpoint | 30 Days | 4 Months |
|---|---|---|
| MACE (%) | 1 | 2 |
| Death (%) | 0 | 0 |
| MI (%) | 1 | 1 |
| TLR (%) | 0 | 1 |
QCA results at 4-month follow-up were also good, with low rates of late loss at the stented site and in all of the segments (Table 3). IVUS analysis found no incidence of late acquired incomplete apposition and an increase in external elastic membrane volume at 4 months (Table 4).
Table 3. ENDEAVOR I: QCA Results
| Measure | In-stent | In-segment |
|---|---|---|
| Reference vessel diameter (mm) |
|
2.96 ± 0.47 |
| Lesion length (mm) |
|
10.9 ± 3.1 |
| MLD (postprocedure) (mm) | 2.84 ± 0.35 | 2.52 ± 0.42 |
| MLD (4 months) (mm) | 2.52 ± 0.43 | 2.31 ± 0.44 |
| Late loss (mm) | 0.33 ± 0.35 | 0.20 ± 0.40 |
| Measure | Post Mean |
4-Month Follow-up Mean |
|---|---|---|
| EEM volume (mm) | 300 | 321 |
| Stent volume (mm) | 142 | 149 |
| Neointimal volume (mm) | -- | 6.1 |
| Percent volume obstruction (%) | NA | 4.5 |
| Late acquired incomplete apposition | -- | 0 |
Investigators concluded that:
The ABT-578 and PC-coated Driver cobalt alloy stent phase 1 study has shown excellent acute device results.
The stent had minimal intimal proliferation with negligible edge effects and low rates of TLR and target vessel revascularization.
This is a very important step toward the incorporation of a new drug-eluting stent into this very exclusive club. We need to take into account that this was not a randomized study and it was done in very simple lesions. Nevertheless, these preliminary results are very promising, and the real proof will come from the pending ENDEAVOR II trial, which will randomize patients to either the bare-metal Driver stent or the ABT-578-coated Endeavor stent.
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