Long-Term Data from DES Clinical Studies Published

June 1, 2011—Long-term follow-up data from three major clinical trials investigating drug-eluting stents have been published. In Catheterization and Cardiovascular Interventions, Scot Garg, MD, et al reported the 4-year clinical outcomes of the SPIRIT II study (2011;77:1012–1017). In the Journal of the American College of Cardiology: Cardiovascular Interventions, Gregg W. Stone, MD, et al published the final 5-year analysis from the Boston Scientific's TAXUS clinical trial program (2011;4:530–542). Also, in the Journal of the American College of Cardiology: Cardiovascular Interventions, David E. Kandzari, MD, et al published 5-year follow-up of the ENDEAVOR III randomized controlled trial (2011;4:543–550).

SPIRIT II
According to the SPIRIT II investigators, SPIRIT II randomized 300 patients to treatment with the Xience V everolimus-eluting stent (EES, Abbott Vascular, Santa Clara, CA), or the Taxus paclitaxel-eluting stent (Boston Scientific Corporation, Natick, MA). At 4-year clinical follow-up, which was available in 256 (85.3%) patients, treatment with the Xience device versus Taxus led to a trend for lower rates of ischemia-driven major adverse cardiovascular events, a composite of cardiac death, myocardial infarction (MI), and ischemia-driven target lesion revascularization (TLR) (7.7% vs 16.4%; P = .056). Also, the Xience V compared with the Taxus resulted in a trend toward lower rates of cardiac death and numerically lower rates of MI, ischemia-driven TLR, and stent thrombosis. Overall, this study reports numerically fewer clinical events in patients treated with Xience V at 4-year follow-up, which is consistent with results from earlier follow-up, the investigators concluded.

TAXUS
As detailed in the Journal of the American College of Cardiology: Cardiovascular Interventions, the completed 5-year databases from the prospective, randomized, double-blind TAXUS I, II, IV, and V trials were pooled for a patient-level analysis.

According to the TAXUS investigators, these studies sought to evaluate the clinical outcomes of the slow-release Taxus paclitaxel-eluting stent (PES) versus an otherwise identical bare-metal stent (BMS). The investigators noted that previous studies were not individually powered to generate reliable estimates of low-frequency safety endpoints or to characterize the long-term safety and efficacy profile of PES.

The TAXUS investigators reported that the study population comprised 2,797 randomized patients (1,400 PES and 1,397 BMS). At the end of the 5-year study period, PES compared with BMS significantly reduced the rate of ischemia-driven TLR (12.3% vs 21%; P < .0001), with consistent reductions across high-risk subgroups and in patients with and without routine angiographic follow-up. There were no significant differences between the stent types in the 1-year or cumulative 5-year rates of death or MI. However, the rate of cardiac death or MI between 1 and 5 years was increased with PES (6.7% vs 4.5%; P = .01), as was stent thrombosis (protocol definition: 0.9% vs 0.2%; P = .007; Academic Research Consortium definition: 1.4% vs 0.9%; P = .18).

The investigators concluded that in this pooled patient-level analysis from the prospective, randomized, double-blind TAXUS trials, PES compared with BMS resulted in a durable 47% reduction in the 5-year rate of ischemia-driven TLR in simple and complex lesions, with nonsignificant differences in the cumulative 5-year rates of death or MI. Between 1 and 5 years, however, the rates of cardiac death or MI and protocol-defined stent thrombosis were increased with PES.

ENDEAVOR III
As detailed in the Journal of the American College of Cardiology: Cardiovascular Interventions, ENDEAVOR III sought to compare late safety and efficacy outcomes following percutaneous coronary revascularization with the Endeavor zotarolimus-eluting coronary stent system (ZES) (Medtronic, Inc., Minneapolis, MN) versus the Cypher sirolimus-eluting coronary stent system (SES) (Cordis Corporation, Bridgewater, NJ) in de novo native coronary artery lesions.

The investigators stated that the background of the study is that despite higher late lumen loss and binary restenosis with ZES compared with SES, it is uncertain whether differences in early angiographic measures translate into more disparate late clinical events.

In the study, clinical outcomes were prospectively evaluated through 5 years in the ENDEAVOR III that randomized 436 patients of relatively low anatomic and clinical risk to treatment with ZES (n = 323) or SES (n = 113) and evaluated a primary endpoint of 8-month angiographic late lumen loss.

The investigators reported for that for ZES versus SES at 5 years (completeness of follow-up: 95.2%), prespecified endpoints of all-cause mortality (5.2% vs 13%; P = .02), MI (1% vs 4.6%; P = .03), and the composite event rates of cardiac death/MI (1.3% vs 6.5%; P = .009), and major adverse cardiac events (14% vs 22.2%; P = .05) were significantly lower among patients treated with ZES. Also, comparing ZES versus SES, rates of target lesion (8.1% vs 6.5%; P = .68) and target vessel revascularization were similar between treatment groups. Stent thrombosis was infrequent and similar in both groups (0.7% vs 0.9%; P = 1). Between 9 months and 5 years, progression of major adverse cardiac events was significantly more common with SES than with ZES (16.7% vs 7.8%; P = .015).

The investigators concluded that despite initially higher angiographic late lumen loss, rates of clinical restenosis beyond the protocol-specified angiographic follow-up period remained stable with ZES compared with the rates for SES, resulting in similar late-term efficacy. Over 5 years, significant differences in death, MI, and composite endpoints favored treatment with ZES, the investigators stated.