Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System IV - SPIRIT IV: 2-Year Follow-Up

Description:

The SPIRIT I, II, and III trials have demonstrated the safety and efficacy of the everolimus-eluting stent (EES) for the treatment of coronary artery disease (CAD). The current trial sought to compare clinical endpoints between the EES and paclitaxel-eluting stent (PES), Taxus Express.

Hypothesis:

EES would be superior compared with PES in the reduction of target lesion failure (TLF) through 1 year.

Study Design

  • Stratified

Patients Enrolled: 3,687
Mean Follow Up: 1 year, then 2 years
Mean Patient Age: 63.3 years
Female: 32

Patient Populations:

  • Reference vessel diameter 2.5-3.75 mm
  • Lesion length ≤28 mm
  • Maximum of three lesions with a maximum of two per epicardial vessel

Exclusions:

  • Left main or ostial LAD/left circumflex lesion
  • In or distal to a bypass graft conduit
  • Bifurcation lesion with sidebranch diameter ≥2 mm and ostial diameter stenosis >50% or requiring predilatatation
  • Total occlusion, thrombus, restenosis, excessive tortuosity, angulation, or heavy calcification
  • Prior coronary brachytherapy
  • High probability of additional PCI within 9 months

Primary Endpoints:

  • TLF at 1 year (cardiac death, target vessel MI, ischemia-driven TLR)

Secondary Endpoints:

  • Ischemia-driven TLR at 1 and 2 years
  • Cardiac death or target vessel MI at 1 and 2 years

Drug/Procedures Used:

After initial angiography, patients meeting enrollment criteria were randomized to EES or PES in a 2:1 fashion. Predilatation was mandatory for all lesions.

Concomitant Medications:

All patients received ≥300 mg of aspirin and ≥300 mg of clopidogrel (unless on chronic treatment) prior to randomization. Following percutaneous coronary intervention (PCI), aspirin ≥80 mg daily was continued for at least 5 years, and clopidogrel 75 mg daily for at least 1 year, unless they were at high risk for bleeding.

Principal Findings:

A total of 3,687 patients were enrolled, 2,458 to EES and 1,229 to PES. Baseline characteristics were fairly similar between the two groups. About 32% were diabetics, including 9% who were insulin-dependent. About 21% had prior myocardial infarction (MI), and 28% presented with unstable angina. The lesion was located in the left anterior descending artery (LAD) in about 40% of the patients, and in the right coronary artery in about 35%; multivessel disease was noted in about 25% of the patients. The mean reference vessel diameter was 2.75 mm, and the mean lesion length was 14.7 mm. The mean stented length per lesion was about 22 mm.

The primary endpoint of TLF (cardiac death, target vessel MI, ischemia-driven target lesion revascularization [TLR]) was significantly lower in the EES arm compared with the PES arm (4.2% vs. 6.8%, hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.46-0.82, p = 0.001 for superiority). This was driven primarily by a significant reduction in ischemia-driven TLR (2.5% vs. 4.6%, HR 0.55, 95% CI 0.38-0.78, p = 0.001). Cardiac death or target vessel MI were similar between the two arms (2.2% vs. 3.2%, p = 0.09). All-cause mortality was similar (1.0% vs. 1.3%, p = 0.61), but EES was associated with a significant reduction in MI (1.9% vs. 3.1%, p = 0.02). EES was also associated with a significant reduction in stent thrombosis (Academic Research Consortium [ARC] or probable) at 1 year, as compared with PES (0.2% vs. 0.8%, p = 0.004). The greatest impact of TLF reduction was noted in patients without diabetes mellitus (DM) (p < 0.05).

Two-year follow-up data were available for 3,578 patients (97%). At 730 days, about 96% of patients were on aspirin, and 71% were on clopidogrel. The primary endpoint of TLF at 2 years was still significantly lower in the EES arm (6.9% vs. 9.9%, HR 0.70, 95% CI 0.55-0.89, p = 0.003). Similarly, ischemia-driven TLR (4.5% vs. 6.9%, p = 0.004) and MI (2.5% vs. 3.9%, p = 0.02) were lower in the EES arm at 2 years. Definite stent thrombosis, based on protocol definition, was also lower at 2 years (0.33% vs. 0.99%, p = 0.02), including late stent thrombosis beyond 1 year (0.09% vs. 0.17%). Similarly, ARC-defined definite or probable stent thrombosis at 2 years was also lower (0.42% vs. 1.23%, p = 0.008), including late stent thrombosis beyond 1 year (0.13% vs. 0.17%). At 2 years, the greatest impact of TLF reduction was once again noted in nondiabetic patients (5.9% vs. 9.7%, p = 0.0005).

Interpretation:

The results of this trial indicate that revascularization of CAD with an EES is superior to PES in reducing TLF, MI, and stent thrombosis at 1 year. Earlier studies had demonstrated a greater reduction in late lumen loss with EES. The current trial demonstrates that low late lumen loss can be achieved with EES without a concomitant increase in stent thrombosis. Reduction in clinical endpoints in the diabetic strata was not noted.

Two-year results demonstrate consistently better outcomes with EES compared with PES, including TLF, MI, and stent thrombosis. Similar results were noted in the 2-year results of the COMPARE trial. Longer-term follow-up and comparison of second-generation DES to third-generation DES/bioabsorbable stents are eagerly awaited.

References:

Stone GW, Rizvi A, Sudhir K, et al., on behalf of the SPIRIT IV Investigators. Randomized Comparison of Everolimus- and Paclitaxel-Eluting Stents: 2-Year Follow-Up From the SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) IV Trial. J Am Coll Cardiol 2011;Apr 20:[Epub ahead of print].

Stone GW, Rizvi A, Newman W, et al. Everolimus-eluting versus paclitaxel-eluting stents in coronary artery disease. N Engl J Med 2010;362:1663-1674.

Presented by Dr. Gregg Stone at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2009), San Francisco, CA, September 23, 2009.

Presented by Dr. Gregg Stone at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2010), Washington, DC, September 23, 2010.

 

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Myocardial Infarction, Insulin, Follow-Up Studies, Platelet Aggregation Inhibitors, Drug-Eluting Stents, Human Rights, Immunosuppressive Agents, Ticlopidine, Sirolimus, Purinergic P2Y Receptor Antagonists, Paclitaxel, Thrombosis, Confidence Intervals, Diabetes Mellitus


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