Two-Year Data Published from SPIRIT IV, COMPARE: Xience Still Favored Over Taxus

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Long-term results from a pair of large randomized trials show that the clinical superiority of everolimus-eluting stents (EES) over paclitaxel-eluting stents (PES) seen at 1 year is maintained or enhanced at 2 years. In particular, the second-generation devices reduce the incidence of stent thrombosis.

Data from the SPIRIT IV and COMPARE trials, both published online April 20, 2011, ahead of print in the Journal of the American College of Cardiology, were first presented in September 2010 at the annual Transcatheter Cardiovascular Therapeutics symposium in Washington, DC.

Maintaining the SPIRIT

For SPIRIT IV, researchers led by Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), randomized 3,687 patients undergoing PCI for relatively uncomplicated lesions at 66 US sites in a 2:1 ratio to EES (n = 2,458; Xience V, Abbott Vascular, Santa Clara, CA) or PES (n = 1,229; Taxus Express2, Boston Scientific, Natick, MA).

At 1 year there was a 2.7% absolute difference in the primary endpoint of target lesion failure (TLF; composite of cardiac death, target vessel MI, or ischemia-driven TLR) favoring EES over PES (4.0% vs. 6.7%; P = 0.0009).

After 2-year follow-up, available in 97% of patients (n = 3,578), the reduced rate of TLF in the EES group compared with the PES group held steady (3% absolute difference), driven by lower rates of target-vessel MI and ischemia-driven TLR. Cardiac death was numerically lower in EES patients, but the disparity did not reach statistical significance. In addition, the 1-year advantage in the incidence of Academic Research Consortium-defined definite or probable stent thrombosis in favor of EES was maintained, with a 64% reduction at 2 years (table 1).

Table 1. Cumulative Outcomes at 2 Years

 

EES
(n = 2,388)

PES
(n = 1,190)

HR (95% CI)

P Value

Primary Endpoint

6.9%

9.9%

0.70 (0.55-0.89)

0.003

Target-Vessel MI

2.3%

3.5%

0.66 (0.44-0.99)

0.04

Ischemia-Driven TLR

4.5%

6.9%

0.66 (0.50-0.88)

0.004

Cardiac Mortality

0.9%

1.3%

0.73 (0.38-1.40)

0.34

Definite or Probable Stent Thrombosis

0.42%

1.23%

0.36 (0.17-0.79)

0.008


Overall, the differential outcomes between the EES and PES cohorts held steady between years 1 and 2.

In addition, the 2-year TLF advantage for EES vs. PES was consistent across 11 prespecified subgroups, although there was a borderline interaction in patients with or without diabetes (RR 0.93; 95% CI 0.65-1.34 vs. RR 0.61; 95% CI 0.46-0.81; P = 0.08).

According to the authors, the durability of the reduction in clinical restenosis with EES is reassuring given earlier reports from SPIRIT II that showed greater incremental late loss between 6 months and 2 years with EES vs. PES.

They caution, however, that the findings do not necessarily apply to those excluded from the trial, which includes a broad range of ‘real-world’ patients with complex lesions and acute thrombotic syndromes.

COMPARE Adds Generalizability

The issue of generalizability, however, is addressed by the all-comers COMPARE trial. For this study, Pieter C. Smits, MD, PhD, of Maasstad Ziekenhuis (Rotterdam, The Netherlands), and colleagues randomized 1,800 consecutive patients who underwent elective or emergent PCI at their institution between February 2007 and September 2008 to EES (n = 897) or PES (n = 903; Taxus Liberté, Boston Scientific). Most lesions were complex (74% type B2 or C), resulting in a mean stented length of 28 mm in both groups.

At 1 year, the primary endpoint (composite of all-cause death, MI, and TVR) was reduced by 31% in the EES group vs. the PES group.

By 2 years, the initial 3% absolute difference between the EES and PES groups for the primary endpoint had increased to 4.7%. Likewise, the disparity in the rates of the secondary endpoint  (composite of cardiac death, nonfatal MI, and clinically driven TLR) widened. However, as at 1- year follow-up, rates of cardiac death did not differ between the groups. EES patients continued to benefit from a reduction in Academic Research Consortium-defined definite or probable stent thrombosis (table 2).

Table 2. Cumulative Outcomes at 2 Years

 

EES
(n = 897)

PES
(n = 903)

RR (95% CI)

P Value

Primary Endpoint

9.0%

13.7%

0.66 (0.50-0.86)

0.002

Cardiac Death, Nonfatal MI, and Clinically Driven TLR

7.4%

11.3%

0.65 (0.48-0.88)

0.004

Nonfatal MI

3.9%

7.5%

0.52 (0.35-0.77)

< 0.001

Clinically Driven TLR

2.6%

5.9%

0.44 (0.27-0.71)

< 0.001

Cardiac Death

2.2%

1.8%

1.26 (0.66-2.41)

0.49

Definite or Probable Stent Thrombosis

0.9%

3.9%

0.23 (0.11-0.49)

< 0.001

 
Importantly, just as stent thrombosis was less common in the EES group than the PES group in the 1-year analysis (significantly so during the first 30 days), the complication continued to occur less frequently with EES between years 1 and 2 (0.3% vs. 1.4% with PES; P = 0.01). The difference was seen despite lower prevalence of dual antiplatelet therapy in the EES group compared with the PES group over the second year (11.4% vs. 15.2%; P = 0.02).

Similar to the SPIRIT IV findings, the reduction in the primary endpoint achieved by implantation of EES was consistent across 9 demographic and angiographic subgroups except for diabetic patients. For the latter, there was no difference in the primary endpoint between the stents at both 1-year and 2-year follow-up. However, further analysis revealed a higher rate of TVR in diabetic patients receiving PES than in those receiving EES (9.3% vs. 2.0%; P = 0.008).

SPIRIT IV, COMPARE Complementary

In an accompanying editorial, Fernando Alfonso, MD, PhD, and Cristina Fernandez, MD, PhD, of Clinico San Carlos University Hospital (Madrid, Spain), address the similarities and differences between the 2 trials. They note that the COMPARE cohort had worse clinical and angiographic baseline characteristics, but SPIRIT IV included more diabetics (32% vs. 18% in COMPARE).

Attempting to explain why the EES advantage over PES increased between the first and second year of follow-up in COMPARE but not in SPIRIT IV, the authors suggest that “a complex clinical/anatomic scenario [as in COMPARE] may be required to unravel subtle late clinical differences among DES.”

Drs. Alfonso and Fernandez characterize SPIRT IV as primarily an efficacy trial (done under relatively ideal conditions) and COMPARE as a pragmatic trial (performed under “real-world” circumstances). “Although this classification might be too simplistic,” they say, “the combined analysis of both trials would take the best of each worlds since efficacy trials maximize internal validity (true estimation of the association between the intervention and outcome), whereas effectiveness trials emphasize external validity (generalizability of results).”

In an email communication with TCTMD, Dr. Stone agreed that the 2 trials complement each other, adding, “The fact that the results were so consistent and markedly positive strongly favors EES compared to PES.” In particular, he noted, the low rate of stent thrombosis with EES is “a very reassuring finding, suggesting that this stent should be preferred in patients at high risk for stent thrombosis, or in whom prolonged dual antiplatelet therapy is not possible.  

“The last remaining issue is in patients with diabetes,” Dr. Stone continued, “and we’ve shown in a meta-analysis that non-insulin-treated diabetics do benefit with EES compared to PES in terms of lower rates of ischemia-driven TLR. The best device for insulin-treated diabetics is still an open question.”

David E. Kandzari, MD, of Piedmont Heart Institute (Atlanta, GA), agreed, but noted that, because of the similar efficacy of EES and PES among diabetics, many clinicians who regularly use and are comfortable with EES choose the stent for their diabetic patients as well.

Dr. Kandzari said he believes the totality of evidence favoring EES compared with PES has convinced most physicians, and that the shift in practice is reflected in the rapid rise in the US market share for the second-generation stent. At his institution, EES now account for about 75% of clinical practice, he reported.

He predicted, however, that the era of randomized trials designed to show the superiority of 1 DES over another may have come to an end. Event rates with the newer devices are so low that it is nearly impossible to differentiate them clinically. One result of this may be that new stents are adopted more by intuition than by clinical evidence, he concluded.

Note: Dr. Stone is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 


Sources:
1. Stone GW, Rizvi A, Sudhir K, et al. 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;Epub ahead of print.

2. Smits PC, Kedhi E, Royaards K-J, et al. Two-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 LIBERTĖ stent in all-comers: A randomized open label trial) trial. J Am Coll Cardiol. 2011;Epub ahead of print.

3. Alfonso F, Fernandez C. Second-generation drug-eluting stents: Moving the field forward [editorial]. J Am Coll Cardiol. 2011;Epub ahead of print.

 


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Two-Year Data Published from SPIRIT IV, COMPARE: Xience Still Favored Over Taxus

Long term results from a pair of large randomized trials show that the clinical superiority of everolimus eluting stents (EES) over paclitaxel eluting stents (PES) seen at 1 year is maintained or enhanced at 2 years. In particular, the second
Disclosures
  • Dr. Stone reports serving on the scientific advisory boards for and receiving honoraria from Abbott Vascular and Boston Scientific and serving as a consultant for AstraZeneca, Bristol-Myers Squibb/Sanofi, Eli Lilly, Medtronic, and Merck.
  • Funding for COMPARE was provided by unrestricted research grants from Abbott Vascular and Boston Scientific.
  • Dr. Smits reports receiving speakers’ fees from Abbott Vascular.
  • Drs. Alfonso and Fernandez report no relevant conflicts of interest. Dr. Kandzari reports receiving consulting, honoraria, and research grant support from Abbott Vascular, Cordis, and Medtronic.

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