Drug eluting stents, generally coated with either paclitaxel or sirolimus, have revolutionised the practice of interventional cardiology, markedly reducing the incidence of restenosis and the need for repeat procedures. Nevertheless, restenosis still occurs and the slower re-epithelialisation associated with these stents mandates the prolonged use of dual antiplatelet therapy to avoid potentially catastrophic stent thrombosis. Second generation stents have been developed to try and minimise some of these problems with thinner, lower profile struts and more modern drug coatings. One of these is the XIENCE V or PROMUS stent which is coated in the drug everolimus. Early data for this stent has been impressive, with head-to-head studies against the popular paclitaxel eluting stents demonstrating noninferior rates of safety and significantly reduced rates of late lumen loss. These studies however have been criticised due to their angiographic end-points and have not been powered for clinically relevant end-points or to demonstrate superiority for the everolimus stent.
To address these issues, the authors conducted the SPIRIT IV trial recruiting 3687 patients at 66 U.S. sites who were scheduled to undergo elective coronary angioplasty. Patients were randomly assigned to receive either an everolimus or paclitaxel stent in a single-blind fashion and all follow-up was conducted by investigators blinded to the treatment allocation. The primary end point was the 1-year composite rate of target-lesion failure (defined as cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization) with no routine follow-up angiography undertaken to better reflect real-world practice. The results are impressive with clear superiority of the everolimus-eluting stents with respect to the primary end point (4.2% vs. 6.8%; RR, 0.62; 95% CI, 0.46 to 0.82; P=0.001). Everolimus-eluting stents were also superior with respect to the major secondary end point of the 1-year rate of ischemia-driven target-lesion revascularization (P=0.001) and were noninferior with respect to the major secondary end point of the 1-year composite rate of cardiac death or target-vessel myocardial infarction (P<0.001 for noninferiority; P=0.09 for superiority). Interestingly, the 1-year rates of myocardial infarction and stent thrombosis were also lower with everolimus-eluting stents than with paclitaxel-eluting stents (1.9% vs. 3.1%, P=0.02 for myocardial infarction; 0.17% vs. 0.85%, P=0.004 for stent thrombosis). Somewhat disappointingly however, while the reduction in target-lesion failure was consistently seen in 12 prespecified subgroups, there was no benefit seen in patients with diabetes, a group who have particularly aggressive coronary disease and are prone to restenosis.
A cost benefit analysis is pending and whether the reduction in restenosis is beneficial when compared with the increased up-front cost of the stent remains to be seen. Further work also needs to be undertaken to ascertain whether the improvements in outcome stem from the improved stent design or the new drug, although a combination of the two factors seems likely. However, after the disappointing data surrounding the second generation zotarolimus-eluting stent, this is certainly a welcome progression for the field.
In this randomised trial of patients undergoing elective coronary angioplasty, an everolimus-eluting stent was seen to show clear superiority over a paclitaxel-eluting stent at one year-follow up.
• Everolimus-Eluting versus Paclitaxel-Eluting Stents in Coronary Artery Disease. Stone GW, Rizvi A, Newman W, Mastali K, Wang JC, Caputo R, Doostzadeh J, Cao S, Simonton CA, Sudhir K, Lansky AJ, Cutlip DE and Kereiakes DJ. N Engl J Med 2010;362:1663-74.