A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice - COMPARE

Description:

The current trial sought to compare outcomes between the everolimus-eluting stent (EES) (Xience V) and paclitaxel-eluting stent (PES) (Taxus Liberte) in a real-world situation.

Contribution to the Literature: The COMPARE trial showed that EES is superior to PES at 5 years for MI, TVR, stent thrombosis, and MACE when used in a real-world setting.

Study Design

Patients Enrolled: 1,800
Mean Follow Up: 1 year, 2 years, and 5 years
Female: 30%

Patient Populations:

  • Patient is suitable candidate for PCI
  • Life expectancy >5 years

Exclusions:

  • No dual antiplatelet therapy for 1 year
  • Cardiogenic shock at presentation
  • Planned major surgery within 1 month
  • Participation in another trial

Primary Endpoints:

  • All-cause mortality, nonfatal MI, and TVR at 1 year

Secondary Endpoints:

  • Cardiac death, nonfatal MI, and ischemia-driven TLR at 1 year, and then annually up to 5 years 
  • All-cause mortality, nonfatal MI, and TVR at 2-5 years
  • Incidence of stent thrombosis annually during 5 years

Drug/Procedures Used:

Patients meeting enrollment criteria were randomized to receive either EES or PES in a 1:1 fashion.

Concomitant Medications:

Glycoprotein IIb/IIIa inhibitors (32%); aspirin 300 mg once, then 100 mg daily for life; clopidogrel 300 or 600 mg once, then 75 mg daily for 12 months

Principal Findings:

A total of 1,800 patients were randomized, 903 to PES and 897 to EES. Baseline characteristics were fairly similar between the two arms. About 25% of patients presented with acute myocardial infarction (MI), and 23% with non-ST-elevation MI. Multivessel disease was noted in 27% of the patients, and 18% were diabetic. Left main stenting was conducted in 2% of the patients. The mean stent length per lesion was 28 mm, and the mean number of lesions was 1.65 per patient.

The primary endpoint of major adverse cardiac events (MACE) at 1 year (all-cause mortality, nonfatal MI, and target vessel revascularization [TVR]) was significantly lower in the EES arm compared with PES (6.2% vs. 9.1%, hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.50-0.95, p = 0.023). Similarly, the incidence of death, MI, and target lesion revascularization (TLR) at 1 year was significantly lower in the EES arm compared with PES (4.9% vs. 8.2%, HR 0.60, 95% CI 0.42-0.86, p = 0.005).

In addition, the incidence of nonfatal MI (2.8% vs. 5.4%, p = 0.007) and TVR (2.4% vs. 6.0%, p = 0.0001) was significantly lower in the EES arm. The incidence of stent thrombosis at 1 year was also significantly lower in the EES arm (0.7% vs. 2.6%, HR 0.26, 95% CI 0.11-0.64, p = 0.002). This was mainly due to a reduction in early stent thrombosis (p = 0.002), rather than late stent thrombosis (p = 0.25).

Follow-up at 2 years was available for 1,795 patients. Only 15.2% and 11.4% of patients were on dual antiplatelet therapy beyond 1 year of index procedure, respectively (p = 0.02). The primary endpoint of MACE at 2 years was still significantly lower in the EES arm compared with PES (9.0% vs. 13.7%, HR 0.66, 95% CI 0.50-0.86, p = 0.0016). The incidences of MI (3.9% vs. 7.5%, p < 0.0001), TVR (3.2% vs. 8.0%, p < 0.0001), and stent thrombosis (0.9% vs. 3.9%, p < 0.0001), including late stent thrombosis (0.3% vs. 1.4%, p = 0.01), at 2 years were significantly lower in the EES arm, although only about 13% of the patients were on dual antiplatelet therapy beyond 1 year.

Follow-up at 5 years was completed in 1,791 (99.5%) patients. MACE for EES vs. PES, respectively, was 8.4% vs. 25.1% (p = 0.0005). MI occurred in 7.0% vs. 11.5% (p = 0.001). TVR occurred in 7.4% vs. 11.4% (p = 0.003). Mortality was 9.0% vs. 10.3% (p = 0.36). Definite/probable stent thrombosis occurred in 3.1% vs. 5.9% (p = 0.005). Differences between the two groups were lower after the first year, and minimal after the third year.

Interpretation:

The results of this trial indicate that EES is superior to PES (Taxus Liberte) in the reduction in clinical endpoints including MACE, nonfatal MI, and stent thrombosis at 5 years, when utilized in a real-world situation. These results are similar to those of the recently presented SPIRIT IV trial. 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, as compared with PES.

Two-year results show persistently better outcomes with EES compared with PES, including MACE, MI, and stent thrombosis. Beyond 1 year, when most patients were not on dual antiplatelet therapy, there was still a significant reduction in stent thrombosis with EES, as compared with PES. These findings are very important, and suggest that second-generation drug-eluting stents (DES) seem to have been successful in at least partially overcoming one of the biggest bete noire's of the first-generation stents: late stent thrombosis. Further long-term follow-up, and the performance of these second-generation DES, as compared with third-generation/bioabsorbable stents, is eagerly awaited.

References:

Smits PC, Vlachojannis GJ, McFadden EP, et al. Final 5-Year Follow-Up of a Randomized Controlled Trial of Everolimus- and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice: The COMPARE Trial (A Trial of Everolimus-Eluting Stents and Paclitaxel Stents for Coronary Revascularization in Daily Practice). JACC Cardiovasc Interv 2015;8:1157-65.

Smits PC, Kedhi E, Royaards KJ, et al. 2-Year Follow-Up of a Randomized Controlled Trial of Everolimus- and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice: The COMPARE (Comparison of the everolimus eluting XIENCE-V stent with the paclitaxel eluting TAXUS LIBERTE stent in all-comers: a randomized open label trial) Trial. J Am Coll Cardiol 2011;Apr 20:[Epub ahead of print].

Kedhi E, Joesoef KS, McFadden E, et al. Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial. Lancet 2010;375:201-9.

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

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

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Interventions and Coronary Artery Disease

Keywords: Paclitaxel, Coronary Artery Disease, Myocardial Infarction, Thrombosis, Drug-Eluting Stents, Percutaneous Coronary Intervention, Life Expectancy, Sirolimus, Diabetes Mellitus, Stents


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