Follow-Up Data Published for SIRTAX, COMPARE, and SPIRIT IV DES Trials

June 21, 2011—Follow-up data from three major drug-eluting stent (DES) trials have been published.

In Circulation, Lorenz Räber, MD, published 5-year clinical and angiographic outcomes of the randomized SIRTAX (Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization) LATE trial (2011;123:2819-2828).

The Journal of the American College of Cardiology published results from two DES studies that were first presented in September 2010 at the Transcatheter Cardiovascular Therapeutics scientific symposium Washington, DC. Pieter C. Smits, MD, et al published 2-year follow-up of from the COMPARE trial (2011;58:11–18). Gregg W. Stone, MD, et al published 2-year follow-up from the SPIRIT IV trial (2011;58:19–25).

SIRTAX LATE

As part of the SIRTAX LATE study, the investigators analyzed clinical and angiographic outcomes of sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) at 5 years to address the need for long-term comparative data of first-generation DES.

As detailed in Circulation, the study randomly assigned 1,012 patients to SES or PES. Repeat angiography was completed in 444 of 1,012 patients (43.8%) at 5 years. Major adverse cardiac events occurred in 19.7% of SES-treated patients and in 21.4% of PES-treated patients (hazard ratio, 0.89; 95% confidence interval [CI], 0.68–1.17; P = .39) at 5 years.

The investigators found that there were no differences between SES and PES in terms of cardiac death (5.8% vs 5.7%; P = .35), myocardial infarction (MI) (6.6% vs 6.9%; P = .51), and target lesion revascularization (TLR) (13.1% vs 15.1%; P = .29). Between 1 and 5 years, the annual TLR rate was 2% (95% CI, 1.4%–2.6%) for SES and 1.4% (95% CI, 0.9%–2%) for PES.

Among patients undergoing paired angiography at 8 months and 5 years, delayed lumen loss amounted to 0.37 ± 0.73 mm for SES and 0.29 ± 0.59 mm for PES (P = .32). The overall rate of definite stent thrombosis was 4.6% for SES and 4.1% for PES (P = .74), and very late definite stent thrombosis occurred at an annual rate of 0.65% (95% CI, 0.4%–0.9%).

The SIRTAX LATE investigators concluded that long-term follow-up of first-generation DES shows no significant differences in clinical and angiographic outcomes between SES and PES. The continuous increase in late lumen loss in conjunction with the ongoing risk of very late stent thrombosis suggests that vascular healing remains incomplete up to 5 years after implantation of first-generation DES, stated the investigators in Circulation.

COMPARE

According to the COMPARE investigators, the purpose of the study was to compare the safety and efficacy of the Xience V everolimus-eluting stent (Abbott Vascular, Santa Clara, CA) with the Taxus Liberté PES (Boston Scientific Corporation, Natick, MA) at 2-year follow-up. At 1-year follow-up, the randomized open-label trial demonstrated a superior clinical outcome for Xience V over Taxus Liberté trial in an all-comers patient population. The investigators sought to determine whether this superiority was maintained after dual-antiplatelet therapy was discontinued after 12 months.

In the study, patients undergoing percutaneous coronary intervention with limited exclusion criteria were randomly allocated to Xience V or Taxus Liberté. The 2-year prespecified endpoints are composites of safety and efficacy and stent thrombosis.

The COMPARE investigators reported that follow-up was completed in 1,795 of 1,800 patients (99.7%). The groups had similar baseline characteristics. At 2 years, significantly fewer Xience V patients took dual-antiplatelet therapy (11.4% vs 15.4%; P = .02). The primary composite of all death, nonfatal MI, and target vessel revascularization (TVR) occurred in 9% of Xience V patients and 13.7% of Taxus Liberté patients (relative risk [RR]: 0.66; 95% CI, 0.5–0.86) driven by a lower rate of MI (3.9% vs 7.5%; RR: 0.52; 95% CI, 0.35–0.77) and TVR (3.2% vs 8%; RR: 0.41; 95% CI, 0.27–0.62), in parallel with a lower rate of definite or probable stent thrombosis (0.9% vs 3.9%; RR: 0.23; 95% CI, 0.11–0.49). Differences significantly increased between 1- and 2-year follow-up for the primary composite endpoint (P = .04), TVR (P = .02), and definite or probable stent thrombosis (P = .02).

The substantial clinical benefit of the Xience V over the Taxus Liberté with regard to measures of both safety and efficacy is maintained at 2 years in real-life practice with an increasing benefit in terms of safety and efficacy between 1 year and 2 years, the investigators concluded.

SPIRIT IV

The SPIRIT IV clinical evaluation comparing the Xience V device and PES sought to determine whether the differences in outcomes present at 1 year were sustained with longer-term follow-up. The investigators concluded that the benefits of Xience V compared with those of PES present at 1 year were sustained at 2 years in this a large-scale, prospective, multicenter, randomized trial.

In the 1-year SPIRIT IV results, the patients undergoing percutaneous coronary intervention who were randomized to Xience V compared with PES experienced lower rates of target lesion failure (cardiac death, target vessel MI, or ischemia-driven TLR), with significant reductions in the individual rates of MI, TLR, and stent thrombosis.

The SPIRIT IV investigators prospectively randomized 3,687 patients with up to three noncomplex previously untreated native coronary artery lesions to Xience V versus PES at 66 United States sites. Follow-up through 2 years is complete in 3,578 patents (97%).

Treatment with the Xience V everolimus-eluting stent compared with PES reduced the 2-year rates of target lesion failure (6.9% vs 9.9%; P = .003), all MI (2.5% vs 3.9%; P = .02), Q-wave MI (0.1% vs 0.8%; P = .002), stent thrombosis (0.4% vs 1.2%; P = .008), and ischemia-driven TLR (4.5% vs 6.9%; P = .004), with nonsignificantly different rates of all-cause and cardiac mortality. Between 1 year and 2 years, there were no significant differences in adverse event rates between the two types of stents, reported the SPIRIT IV investigators in the Journal of the American College of Cardiology.