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A new-generation zotarolimus-eluting stent (ZES) continues to show strong safety and efficacy outcomes similar to those of a second-generation everolimus-eluting stent (EES) at 4 years in ‘real world’ coronary artery disease (CAD) patients, according to a study published online February 12, 2014, ahead of print in the Journal of the American College of Cardiology. Moreover, target lesion revascularization (TLR) accounts for less than half of all revascularizations after the index intervention, suggesting that ongoing medical management is as important as initial stent choice, the authors say.

Four-year results from the RESOLUTE All Comers trial were originally presented at EuroPCR in Paris, France, in May 2013.

The original multicenter trial randomized 2,292 patients with symptomatic stable CAD or ACS to the Resolute ZES (n = 1,140; Medtronic, Santa Rosa, CA) or the Xience V EES (n = 1,152; Abbott Vascular, Santa Clara, CA). At 13 months, the ZES was noninferior to the EES, with similar rates of the primary endpoint of TVF (cardiac mortality, target-vessel MI, and clinically indicated TLR; 8.2% vs 8.3%; P for noninferiority < 0.001).

Resolute has the same design as the Endeavor stent, except that instead of a phosphorylcholine polymer, it uses a tripolymer coating to extend drug release, thus minimizing neointimal hyperplasia and potentially reducing inflammatory response. 

Final Follow-up 

In the current paper, investigators led by Stephan Windecker, MD, of Bern University Hospital (Bern, Switzerland), report 4-year outcomes for 1,122 (98.4%) ZES patients and 1,124 (97.6%) EES patients. Baseline clinical and angiographic characteristics were well balanced between the groups.

No differences were seen between ZES and EES patients in rates of TLF (primary endpoint), TVF or its components, any revascularization, or ARC-defined definite or probable stent thrombosis (table 1).

Table 1. Outcomes at 4 Years

^a All-cause death, any MI, and any revascularization.

Landmark analysis showed that very late stent thrombosis was uncommon, although the incidence rose slightly between years 1 and 4. No differences in adherence to dual antiplatelet therapy were observed between the groups throughout 4 years.

At 4 years, all cases of TLR occurred in 8.6% of patients. Clinical and angiographic factors predicting such procedures were:

• Younger age: OR 0.98; P = 0.003
• Insulin-treated diabetes: OR 1.97; P = 0.004
• Higher Syntax score: OR 1.03; P < 0.001
• Saphenous vein graft treatment: OR 2.28; P = 0.024
• Ostial lesion treatment: OR 2.17; P = 0.003
• In-stent restenosis treatment: OR 2.44; P < 0.001

Predictors for any revascularization largely overlapped those for TLR, except that diabetes replaced insulin-treated diabetes and previous PCI and STEMI, smaller reference vessel diameter, and treatment of the LAD and RCA were added.

Noting that TLR events represented much less than half of all repeat revascularizations, the authors conclude that “optimization of secondary prevention and medical management appear as important as the initial choice between different types of new-generation DES.”

Moreover, Dr. Windecker and colleagues observe that the predictors of future events for the newer DES are similar to those for earlier-generation devices suggests that the efficacy of the former are limited by the same clinical and angiographic characteristics.

“The newer DES continue to show remarkable safety and efficacy, with no obvious differences between [ZES and EES] for any of the study endpoints,” Dimitrios Karmpaliotis, MD, PhD, of Columbia University Medical Center (New York, NY), told TCTMD in a telephone interview.

Complexity of Study Population Underscored

An important aspect of the trial, he pointed out, is that stents were used off-label in about 60% of cases. While pivotal trials evaluating new devices are highly selective, this all-comers study consists of a more complex population—although it does not fully match the complexity of patients stented today, he noted. Moreover, stenting of some subsets of lesions, such as vein grafts, ostial lesions, and in-stent restenoses, as well as of patients, such as diabetics, remains challenging, he added.

By extending follow-up through 4 years, Dr. Karmpaliotis said, the investigators were keeping an eye out for very late stent thrombosis, which turned out to be rare. Another motive for taking a longer view, he observed, is that in earlier trials follow-up angiography was performed at 8 months to 1 year based on the assumption that that was the period of highest vulnerability to in-stent restenosis. “But we learned the hard way that in-stent restenosis is a continuous process—it can occur after a year,” he commented. “So they wanted to look at that as well.”

Stents Are Not the End of Treatment

One revealing finding is that more than half of the events that occurred over 4 years were not related to stent implantation, Dr. Karmpaliotis observed. “That tells us that stents are pretty good but that coronary atherosclerosis is a progressive disease and we need to continue to be very aggressive with medical management,” he noted.

Another implication of the excellent results, Dr. Karmpaliotis said, is that the newer-generation DES “set the bar quite high for any new technologies. It is now very difficult to make any dramatic breakthroughs in stent [design].”

Study Details 

Dual antiplatelet therapy with daily clopidogrel (75 mg) and aspirin (≥ 75 mg) was prescribed for at least 6 months with aspirin use to continue indefinitely. 

 

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Source:
Taniwaki M, Stefanini GG, Silber S, et al. Four year clinical outcomes and predictors of repeat revascularization in patients treated with new generation drug-eluting stents in the RESOLUTE All Comers randomized trial. J Am Coll Cardiol. 2014;Epub ahead of print.

 

 

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