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Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions - SPIRIT III
Description:
The goal of the trial was to evaluate treatment with an everolimus-eluting stent compared with a paclitaxel-eluting stent among patients undergoing elective percutaneous coronary intervention (PCI) for de novo coronary lesions.
Hypothesis:
The everolimus-eluting stent will be similar or superior to the paclitaxel-eluting stent in reducing angiographic in-segment late loss.
Study Design
- Randomized
- Parallel
Patients Enrolled: 1,002
Mean Follow Up: 8 months, 2 years, and 5 years
Mean Patient Age: 63 years
Female: 31%
Patient Populations:
- One or two de novo coronary lesions with a 2.5-3.75 mm reference diameter and lesion length <28 mm in up to two coronary arteries (one lesion maximum per vessel)
Exclusions:
- Planned (or prior) PCI in the target or nontarget vessel within 9 months after the index procedure
- Prior coronary brachytherapy
- Recent MI
- Left ventricular dysfunction (ejection fraction <30%)
- Organ transplantation
- Chemotherapy for malignancy, known immunologic or autoimmune disease, or prescribed immunosuppressive medication
- Need for chronic anticoagulation
- Contraindications to any of the study medications or components of drug-eluting stents
- Need for elective surgery within 9 months after the procedure that would require discontinuation of antiplatelet medications
- Abnormal platelet count (<100,000 or >700,000) or abnormal white blood cell count (<3,000)
- Renal insufficiency (creatinine >2.5 mg/dl)
- Liver disease
- Recent major bleed, hemorrhagic diathesis, or objection to blood transfusion
- Stroke or transient ischemic attack within 6 months
- Comorbid condition with life expectancy <1 year
- Pregnancy, lactation, or planned pregnancy
- Participation in another investigational study
- Ostial, left main, or bifurcation lesion
- Excessive proximal vessel tortuosity or calcification
- Presence of thrombus
- Bypass graft lesion
- Total occlusion
- Lesion diameter stenosis
- Presence of moderate lesions within the target vessel that could require PCI within 9 months
Primary Endpoints:
- In-segment late loss at 8-month angiographic follow-up assessed by noninferiority and superiority
Secondary Endpoints:
- TVF at 9 months, defined as cardiac death, MI, or TVR
- MACE at 9 months and 1 year, defined as cardiac death, MI, or TLR
- Stent thrombosis
- Binary restenosis
- IVUS data (neointimal hyperplasia, percent volume obstruction, incomplete stent apposition)
Drug/Procedures Used:
Patients were randomized 2:1 to an everolimus-eluting stent (n = 669) or a paclitaxel-eluting stent (n = 333). A subset of patients underwent repeat angiographic follow-up at 8 months (n = 564). Among the repeat angiographic cohort, a proportion of patients also underwent intravascular ultrasound (IVUS).
Concomitant Medications:
Periprocedure, patients received at least 300 mg each of aspirin and clopidogrel. Patients were anticoagulated with unfractionated heparin or bivalirudin according to the standard of care, and they could be treated with a glycoprotein IIb/IIIa inhibitor per operator discretion. Post-procedure, patients were treated with aspirin indefinitely (at least 80 mg daily) and clopidogrel (75 mg daily) for at least 6 months.
Principal Findings:
Lesion location was the left anterior descending in 42% of patients. The reference vessel diameter was 2.8 mm, the lesion length was 15 mm, and the mean number of stents per patient was 1.3, in both groups. The total stent length per lesion was 23 mm in the everolimus group and 22 mm in the paclitaxel group (p = 0.02).
The primary endpoint of in-segment late lumen loss at 8 months was smaller in the everolimus group than the paclitaxel group (0.14 mm vs. 0.28 mm, p < 0.001 for noninferiority and p = 0.004 for superiority). In-segment binary restenosis occurred in 4.7% of the everolimus group and 8.9% of the paclitaxel group (p = 0.07).
On IVUS, neointimal hyperplasia volume was 10.1 mm3 in the everolimus group and 20.9 mm3 in the paclitaxel group (p = 0.04). There was no difference in 8-month incomplete apposition (25.6% for everolimus vs. 16.3% for paclitaxel, p = 0.27) or late acquired apposition (1.1% vs. 2.3%, p = 0.54).
There was no difference in the major secondary endpoint of target vessel failure (cardiac death, myocardial infarction [MI], or target vessel revascularization [TVR]) at 9 months (7.2% of the everolimus group and 9.0% of the paclitaxel group; p < 0.001 for noninferiority and p = 0.31 for superiority).
At 1 year, the individual outcomes of cardiac death occurred in 0.5% and 0.3% (p = 0.72), MI in 2.8% and 4.1% (p = 0.33), and TVR in 6.1% and 7.5% (p = 0.41), respectively, for everolimus versus paclitaxel. Stent thrombosis occurred in 0.8% of the everolimus group and 0.6% of the paclitaxel group (p > 0.99).
At 2 years, the individual outcomes of cardiac death occurred in 1.1% and 1.3% (p = 0.75), MI in 3.3% and 5.9% (p = 0.08), target lesion revascularization (TLR) occurred in 6.1% and 11.3% (p = 0.006), and target vessel failure (TVF) occurred in 11.3% and 16.4% (p = 0.04), respectively for everolimus versus paclitaxel. Major adverse cardiac events (MACE) (defined as cardiac death, MI, or TLR) occurred in 7.7% and 13.8% (p = 0.005), respectively for everolimus versus paclitaxel. Cumulative stent thrombosis at 2 years occurred in 1.0% and 1.7% (p = 0.35), whereas very late thromboses (>1-2 years) occurred in 0.2% and 1.0% (p = 0.10), respectively for everolimus and paclitaxel.
At 5 years, TVF occurred in 19.3% for everolimus versus 24.5% for paclitaxel (p = 0.05), ischemia-driven TLR: 8.6% versus 12.1% (p = 0.06), respectively, and all-cause mortality: 5.9% vs. 10.1% (p = 0.02), late stent thrombosis: 0.5% versus 1.0% (p = 0.36), respectively.
Interpretation:
Among patients undergoing elective PCI for de novo lesions, treatment with the everolimus-eluting stent was associated with a reduction in late lumen loss compared with the paclitaxel-eluting stent at 8-month angiographic follow-up.
TVF at 9 months was noninferior for the everolimus stent compared with the paclitaxel stent, although this difference was significant (favoring everolimus) at 2 and 5 years. Clinical follow-up to 2 years revealed the incidence of the individual outcomes of death (significant by 5 years), MI, and stent thrombosis to be numerically similar (although favoring everolimus) between the groups.
Attention should be drawn to the numerous exclusion criteria of the present study since the first-generation drug-eluting stents were quickly adopted into widespread and untested patient populations.
The present study complements the SPIRIT II data (also with 2-year follow-up), which showed a reduction in late lumen loss with the everolimus stent compared with paclitaxel stent in a low-risk, elective PCI population.
References:
Stone GW, Midei M, Newman W, et al. Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease: a randomized trial. JAMA 2008;299:1903-13.
Stone GW, Midei M, Newman W, et al., on behalf of the SPIRIT III Investigators. Randomized comparison of everolimus-eluting and paclitaxel-eluting stents. Two-year clinical follow-up from the Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) III trial. Circulation 2009;119:680-6.
Gada H, Kirtane AJ, Newman W, et al. Five-Year Results of a Randomized Comparison of XIENCE V Everolimus-Eluting and TAXIS Paclitaxel-Eluting Stents: Final Results From the SPIRIT III Trial. JACC Cardiovasc Interv 2013;Nov 13:[Epub ahead of print].
Keywords: Paclitaxel, Complement System Proteins, Myocardial Infarction, Follow-Up Studies, Thrombosis, Drug-Eluting Stents, Attention, Immunosuppressive Agents, Sirolimus, Hyperplasia, Percutaneous Coronary Intervention
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