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Over the long term, a second-generation everolimus-eluting stent (EES) provides superior efficacy and safety compared with a first-generation paclitaxel-eluting stent (PES), according to a meta-analysis of complete data from 3 randomized SPIRIT trials published in the September 2013 issue of JACC: Cardiovascular Interventions.

Exceptions to this pattern are diabetic patients and those with lesions in vessels other than the LAD, where EES and PES show similar rates of target lesion failure (TLF).

Investigators led by George D. Dangas, MD, PhD, of Mount Sinai Medical Center (New York, NY), pooled 3-year patient-level data from the SPIRIT II, III, and IV trials involving 4,989 patients with de novo lesions randomized to the Xience V everolimus-eluting stent (EES; Abbott Vascular, Santa Clara, CA; n = 3,350) or the Taxus paclitaxel-eluting stent (PES; Boston Scientific, Boston, MA; n = 1,639).

Long-term Advantage for EES

Procedural outcomes did not differ between the groups. At 3 years, EES reduced multiple clinical endpoints, including all-cause mortality, MI, ischemia-driven TLR, MACE (cardiac death, MI, or ischemia-driven TLR), ischemia-driven TLR, TLF (cardiac death, target-vessel MI, or ischemia-driven TLR ), and Academic Research Consortium (ARC)-defined stent thrombosis (table 1). 

Table 1. Clinical Outcomes at 3 Years

 
Protocol-defined rates of stent thrombosis were lower with EES vs. PES both within 1 year (0.4% vs. 0.8%; P = 0.04) and between years 1 and 3 (0.5% vs. 1.1%; P = 0.02).

On multivariable analysis, randomization to EES vs. PES was an independent predictor of all individual and composite endpoints. Moreover, the superiority of EES over PES for TLF was consistent across most subgroups. The only interactions with stent type were for diabetic status (P = 0.02) and vessel type (P = 0.03), with TLF rates similar between EES and PES specifically among insulin-dependent diabetics and patients with non-LAD lesions.

“[T]he benefits of EES relative to PES were not only sustained but also continued to increase in magnitude over 3-year follow-up,” the authors observe. Reductions in all-cause death and MI with EES support “the contention that new-generation devices can indeed affect pathobiological processes that may afford improved outcomes in ‘hard endpoints’ over time,” they add.

Reduced Late Stent Thrombosis Key?

The investigators suggest that the mortality benefit of EES may be due in part to a lower rate of very late stent thrombosis. Possible reasons for the second-generation stent’s advantage include:

• Thinner struts
• The fact that everolimus is completely eluted within 90 days, whereas paclitaxel is retained locally in the polymer for a prolonged time
• Potentially greater cytotoxicity of paclitaxel
• Presence of a thromboresistant fluoropolymer
• Greater conformability and thus lower risk of strut fracture with the cobalt chromium EES platform compared with the thicker, stainless steel PES platform

In a telephone interview with TCTMD, Dr. Dangas praised the SPIRIT trials program, noting that the current meta-analysis is able to draw on data from trials that had relatively consistent methodologies and advanced stepwise from a small, highly selected cohort to a large, all-comers population. Pooling these data make it possible to show a mortality advantage for EES even though the individual trials were underpowered for such a hard endpoint, he observed.

While welcoming confirmation of the superiority of EES in the trials’ aggregate population over 3 years of follow-up, David E. Kandzari, MD, of the Piedmont Heart Institute (Atlanta, GA), told TCTMD in a telephone interview that at this point the results are hardly surprising.

End of an Era of DES Comparisons

“Reports like this represent the end of an era of comparisons of newer-generation DES against PES,” he said. “Their real interest lies in looking at the trajectory of outcomes within EES-treated patients over time rather than in comparison with PES.”

The data are also helpful to clinicians not so much in guiding stent choice as in providing a benchmark to share with patients regarding the longer-term outcomes of second-generation DES. “For example, we can now tell patients that the chance of undergoing repeat revascularization over 3 years is on the order of 6%,” he noted.

With regard to the performance of EES in diabetic patients, Dr. Kandzari observed that their diminished efficacy relative to PES has been seen throughout the SPIRIT trials. “Still, a tie is not a win [for PES],” he said, and the totality of evidence favors use of EES in this subgroup.

Dr. Dangas agreed but said the finding nonetheless has important implications for research. Mechanisms of restenosis and progressive atherosclerosis may be different in diabetes. Given the results of the FREEDOM trial, which found that PCI yields higher rates of death and MI in this subgroup compared with CABG, diabetic patients may require special care. Dedicated trials are needed to better understand the performance of various stents in this population, Dr. Dangas added.

Now that PES have largely been phased out of clinical practice, Dr. Kandzari concluded, EES or other second- or third-generation DES will take over as the standard by which to judge new stent designs.

Study Details

Baseline clinical and angiographic characteristics were well matched between the stent groups. There were trends toward fewer unstable angina patients and more ACC/AHA class C lesions in the EES group.

Stent thrombosis was prospectively protocol-defined as ACS with angiographic thrombus within or adjacent to a stent, or in the absence of angiography, any unexplained death or acute MI in the target lesion distribution within 30 days.

Note: Dr. Dangas and principal investigator Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 

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Source:
Dangas GD, Serruys PW, Kereiakes DJ, et al. Meta-analysis of everolimus-eluting versus paclitaxel-eluting stents in coronary artery disease: Final 3-year results of the SPIRIT clinical trials program (Clinical Evaluation of the Everolimus Eluting Coronary Stent System in the Treatment of Patients with De Novo Native Coronary Artery Lesions). J Am Coll Cardiol Intv. 2013;6:914-922.

 

 

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