Randomized comparison of everolimus-eluting and paclitaxel-eluting stents: two-year clinical follow-up from the Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) III trial.

BACKGROUND: In the prospective randomized Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) III trial, an everolimus-eluting stent (EES) compared with a widely used paclitaxel-eluting stent (PES) resulted in a statistically significant reduction in angiographic in-segment late loss at 8 months and noninferior rates of target vessel failure (cardiac death, myocardial infarction, or target vessel revascularization) at 1 year. The safety and efficacy of EES after 1 year have not been reported. METHODS AND RESULTS: A total of 1002 patients with up to 2 de novo native coronary artery lesions (reference vessel diameter, 2.5 to 3.75 mm; lesion length < or =28 mm) were randomized 2:1 to EES versus PES. Antiplatelet therapy consisted of aspirin indefinitely and a thienopyridine for > or =6 months. Between 1 and 2 years, patients treated with EES compared with PES tended to have fewer episodes of protocol-defined stent thrombosis (0.2% versus 1.0%; P=0.10) and myocardial infarctions (0.5% versus 1.7%; P=0.12), with similar rates of cardiac death (0.3% versus 0.3%; P=1.0) and target vessel revascularization (2.9% versus 3.0%; P=1.0). As a result, at the completion of the 2-year follow-up, treatment with EES compared with PES resulted in a significant 32% reduction in target vessel failure (10.7% versus 15.4%; hazard ratio, 0.68; 95% confidence interval, 0.48 to 0.98; P=0.04) and a 45% reduction in major adverse cardiac events (cardiac death, myocardial infarction, or target lesion revascularization; 7.3% versus 12.8%; hazard ratio, 0.55; 95% confidence interval, 0.36 to 0.83; P=0.004). Among the 360 patients who discontinued clopidogrel or ticlopidine after 6 months, stent thrombosis subsequently developed in 0.4% of EES patients versus 2.6% of PES patients (P=0.10). CONCLUSIONS: Patients treated with EES rather than PES experienced significantly improved event-free survival at a 2-year follow-up in the SPIRIT III trial, with continued divergence of the hazard curves for target vessel failure and major adverse cardiac events between 1 and 2 years evident. The encouraging trends toward fewer stent thrombosis episodes after 6 months in EES-treated patients who discontinued a thienopyridine and after 1 year in all patients treated with EES rather than PES deserve further study.

Gender-based evaluation of the XIENCE V everolimus-eluting coronary stent system: clinical and angiographic results from the SPIRIT III randomized trial.

OBJECTIVES: We evaluated the role of gender on clinical and angiographic results of the everolimus-eluting stent in the SPIRIT III trial. BACKGROUND: The SPIRIT III trial demonstrated superior efficacy of the XIENCE V everolimus-eluting stent compared with the TAXUS paclitaxel-eluting stent. Whether these results are applicable to women is unknown. METHODS: A total of 1,002 patients with coronary artery lesions of 28 mm or less long in 2.5-3.75 mm diameter vessels were prospectively randomized to receive percutaneous coronary intervention with either XIENCE V stent or TAXUS stent placement. Post hoc gender subset analysis was performed. RESULTS: A total of 669 patients (200 women) received the XIENCE V stent, and 332 patients (114 women) were assigned to the TAXUS stent. Women were older and had more hypertension and diabetes than men. At 1 year, rates of MACE (11.1% vs. 5.7%, P = 0.004), TVF (13.7% vs. 7.5%, P = 0.003), TVR (10.8% vs. 4.6%, P = 0.0007), and TLR (7.2% vs. 2.7%, P = 0.002) were higher in women compared with men. The difference in 1 year MACE and TVF rates between men and women remained after adjusting for baseline covariates. Although the angiographic characteristics at baseline were similar among the female cohort, women assigned to XIENCE V had lower in-stent late loss (0.19 vs. 0.42 mm, P = 0.01) compared with women treated with the TAXUS stent. Although 30-day clinical outcomes were similar for women treated with XIENCE V and TAXUS stents, at 1 year, women with XIENCE V stents had significantly lower MACE (8.2% vs. 16.1 %, P = 0.04) and TVR (3.1% vs. 8.9%, P = 0.03) compared with those treated with TAXUS stents. Stent thrombosis rates were similar between women receiving either XIENCE V or TAXUS stents. CONCLUSIONS: Women in the SPIRIT III trial had inherently higher MACE and TVF rates than men. However, the angiographic and clinical benefits of using XIENCE V stents are generalizable to women.

Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease: a randomized trial.

CONTEXT: A thin, cobalt-chromium stent eluting the antiproliferative agent everolimus from a nonadhesive, durable fluoropolymer has shown promise in preliminary studies in improving clinical and angiographic outcomes in patients with coronary artery disease. OBJECTIVE: To evaluate the safety and efficacy of an everolimus-eluting stent compared with a widely used paclitaxel-eluting stent. DESIGN, SETTING, AND PATIENTS: The SPIRIT III trial, a prospective, randomized, single-blind, controlled trial enrolling patients at 65 academic and community-based US institutions between June 22, 2005, and March 15, 2006. Patients were 1002 men and women undergoing percutaneous coronary intervention in lesions 28 mm or less in length and with reference vessel diameter between 2.5 and 3.75 mm. Angiographic follow-up was prespecified at 8 months in 564 patients and completed in 436 patients. Clinical follow-up was performed at 1, 6, 9, and 12 months. INTERVENTIONS: Patients were randomized 2:1 to receive the everolimus-eluting stent (n = 669) or the paclitaxel-eluting stent (n = 333). MAIN OUTCOME MEASURES: The primary end point was noninferiority or superiority of angiographic in-segment late loss. The major secondary end point was noninferiority assessment of target vessel failure events (cardiac death, myocardial infarction, or target vessel revascularization) at 9 months. An additional secondary end point was evaluation of major adverse cardiac events (cardiac death, myocardial infarction, or target lesion revascularization) at 9 and 12 months. RESULTS: Angiographic in-segment late loss was significantly less in the everolimus-eluting stent group compared with the paclitaxel group (mean, 0.14 [SD, 0.41] mm vs 0.28 [SD, 0.48] mm; difference, -0.14 [95% CI, -0.23 to -0.05]; P < or = .004). The everolimus stent was noninferior to the paclitaxel stent for target vessel failure at 9 months (7.2% vs 9.0%, respectively; difference, -1.9% [95% CI, -5.6% to 1.8%]; relative risk, 0.79 [95% CI, 0.51 to 1.23]; P < .001). The everolimus stent compared with the paclitaxel stent resulted in significant reductions in composite major adverse cardiac events both at 9 months (4.6% vs 8.1%; relative risk, 0.56 [95% CI, 0.34 to 0.94]; P = .03) and at 1 year (6.0% vs 10.3%; relative risk, 0.58 [95% CI, 0.37 to 0.90]; P = .02), due to fewer myocardial infarctions and target lesion revascularization procedures. CONCLUSIONS: In this large-scale, prospective randomized trial, an everolimus-eluting stent compared with a paclitaxel-eluting stent resulted in reduced angiographic late loss, noninferior rates of target vessel failure, and fewer major adverse cardiac events during 1 year of follow-up. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00180479.

A method to estimate the mean lifetime survival increase of statin therapy.

AIM: To propose a method for estimating the lifetime advantage of statins. METHODS: Kaplan-Meier survival curves from published 4S and LIPID studies with 5.8- and 6.1-year follow-up were digitized. Gompertz distributions were fit up to the end of the trials, and then extrapolated out to the end of the patients' predicted lifetimes for each study. RESULTS: The method results in a 9.9 (95% CI: 8.7-11.9) and 2.8 (95% CI: 2.3-3.3) years' increases for the statin groups for 4S and LIPID studies, respectively. CONCLUSION: Previous analysis of the same data was limited by the trials' relatively short run time. As such, we propose a method for correctly estimating the true effect of statin therapy in terms of total lifetime extension.

An experimental method for the percutaneous induction of a posterolateral infarct and functional ischemic mitral regurgitation.

BACKGROUND AND AIM OF THE STUDY: Appropriate experimental models are needed to study the mechanisms underlying left ventricular (LV) remodeling and functional ischemic mitral regurgitation (IMR). Herein is described an original percutaneous method for inducing a well-defined posterolateral infarct and significant IMR. METHODS: Under videofluoroscopic guidance, the second (OM2) and third (OM3) obtuse marginal branches of the circumflex artery of six sheep were selectively and sequentially injected with 100% ethyl alcohol. Transthoracic echocardiography (TTE) was performed before and after alcohol injection, and weekly until sacrifice at 8 +/- 1.3 weeks. The LV endsystolic (LVESD) and end-diastolic (LVEDD) dimensions, interpapillary distance (M1-M2), mitral annulus diameter (MA), and degree of IMR and ischemic tricuspid regurgitation (ITR) were measured. RESULTS: One animal died from irreversible ventricular fibrillation. In the remaining sheep, a well-defined posterolateral infarct of 22% of the heart mass resulted, followed by 2.8 + IMR and 2.1+ ITR. The mean weight gain was 16%, and all sheep showed signs of heart failure. All echocardiographic parameters were increased: systolic MA by 29%, diastolic MA by 18%, LVEDD by 33%, LVESD by 62%, M1-M2 diastolic by 32%, M1-M2 systolic by 21%, and tethering and tenting distances by 32% and 108%, respectively. CONCLUSION: The percutaneous selective injection of 100% ethyl alcohol in OM2 and OM3 resulted in a well-defined posterolateral infarct and significant IMR and ITR. Because it was a percutaneous procedure, this novel, simple and reproducible method did not require a thoracotomy. This model should facilitate the further study of LV remodeling and IMR.

5-year results of a randomized comparison of XIENCE V everolimus-eluting and TAXUS paclitaxel-eluting stents: final results from the SPIRIT III trial (clinical evaluation of the XIENCE V everolimus eluting coronary stent system in the treatment of patients with de novo native coronary artery lesions).

OBJECTIVES: This study sought to evaluate the long-term safety and efficacy of everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in patients with obstructive coronary artery disease. BACKGROUND: The use of EES compared to PES has been shown to result in improved clinical outcomes in patients undergoing PCI. However, there have been concerns regarding the durability of these benefits over longer-term follow-up. METHODS: SPIRIT III was a prospective, multicenter trial in which 1,002 patients were randomized 2:1 to EES versus PES. Endpoints included ischemia-driven target vessel failure (TVF) (death, myocardial infarction (MI), or ischemia-driven target vessel revascularization [TVR]), the pre-specified primary endpoint), target lesion failure (TLF) (cardiac death, target-vessel MI, or ischemia-driven target lesion revascularization [TLR]), major adverse cardiac events (MACE) (cardiac death, MI, or ischemia-driven TLR), their individual components and stent thrombosis. RESULTS: Five-year follow-up was available in 91.9% of patients. Treatment with EES versus PES resulted in lower 5-year Kaplan-Meier rates of TVF (19.3% vs. 24.5%, p = 0.05), TLF (12.7% vs. 19.0%, p = 0.008), and MACE (13.2% vs. 20.7%, p = 0.007). EES also resulted in reduced rates of all-cause death (5.9% vs. 10.1%, p = 0.02), with nonsignificantly different rates of MI, stent thrombosis, and TLR, and no evidence of late catch-up of TLR over time. CONCLUSIONS: At 5 years after treatment, EES compared to PES resulted in durable benefits in composite safety and efficacy measures as well as all-cause mortality. Additionally, the absolute difference in TLR between devices remained stable over time without deterioration of effect during late follow-up.

Clinical and angiographic outcomes of elderly patients treated with everolimus-eluting versus paclitaxel-eluting stents: three-year results from the SPIRIT III randomised trial.

AIMS: Age is an important determinant of outcomes in patients treated with percutaneous coronary intervention (PCI). This report from the randomised multicentre SPIRIT III trial compares the outcomes in elderly and younger patients treated with everolimus-eluting stent (EES) versus paclitaxel-eluting stent (PES). METHODS AND RESULTS: A total of 1,002 patients with stable or unstable angina or inducible ischaemia undergoing PCI were randomised in a 2:1 ratio to receive EES or PES. Outcomes were examined across the randomised groups as a function of age and stent type. Patients ≥65 years of age (elderly) treated with EES vs. PES had lower in-segment late lumen loss (0.11±0.32 mm vs. 0.38±0.55 mm, respectively, p=0.0002) and lower rates of binary in-segment restenosis (3.4% vs. 15.5%, p = 0.004) at eight months, along with a 48% lower incidence of 3-year target vessel failure (TVF=cardiac death, myocardial infarction and ischaemia-driven target vessel revascularisation [TVR]; 10.8% vs. 20.8%, p=0.009), mainly due to a lower incidence of TVR (5.4% vs. 9.2%, p=0.20). Among EES patients, elderly compared to younger patients had comparable rates of binary in-segment restenosis (3.4% vs. 5.6%, p=0.44) at eight months but paradoxically lower rates of TVF (10.8% vs. 17.1%, p=0.03) at three years. Among PES patients, elderly compared to younger patients had a higher rate of binary in-segment restenosis (15.5% vs. 3.4%, p=0.01) at eight months and no difference in the rate of 3-year TVF (20.8% vs. 19.4%, p=0.77) .There was a significant interaction between stent assignment, age ≥65 years and 8-month angiographic in-segment late loss (p=0.001). CONCLUSIONS: Implantation of both EES and PES appeared to be safe in elderly patients, however EES compared to PES was more effective due to enhanced 3-year MACE- and TVF-free outcomes. Further research should clarify age-specific mechanisms of neointimal response after treatment with drug-eluting stents.

Comparison of everolimus-eluting and paclitaxel-eluting coronary stents in patients with two treated vessels: 2-year results from the SPIRIT III randomised trial.

AIMS: To examine the two year clinical outcomes in dual-vessel disease from the SPIRIT III trial comparing the XIENCE V(r) everolimus-eluting stent (EES) to the TAXUS Express2(tm) paclitaxel-eluting stent (PES). METHODS AND RESULTS: From a total of 1,002 randomised subjects, 103 and 51 patients in the EES and PES groups respectively underwent stenting of two lesions in two vessels (one lesion per epicardial vessel). Two-year event rates were lower in one compared to two-vessel treated patients regardless of stent type. For EES vs. PES, major adverse cardiac events (MACE=cardiac death, MI or TLR) was clinically reduced 35.0% in the single vessel patients (6.5% vs. 9.6%, p=0.09) and was significantly reduced 64% in dual vessel patients (11.9% vs. 30.1%, p=0.006). There was no significant interaction between stent type (EES vs. PES) and the number of stented vessels (two vs. single) for either 2-year TVF and MACE (interaction p values were 0.69 and 0.16, respectively). CONCLUSIONS: In the SPIRIT III randomised trial, patients with both single and dual vessel treatment with EES showed improved clinical outcomes at two years compared to those treated with PES. Follow-up to five years is ongoing.

Side branch occlusion with everolimus-eluting and paclitaxel-eluting stents: three-year results from the SPIRIT III randomised trial.

AIMS AND METHODS: The rates of side branch occlusion and subsequent periprocedural MI during everolimus-eluting stent (EES) and paclitaxel-eluting stent (PES) placement were examined in the randomised SPIRIT III trial. Periprocedural myocardial infarction (MI) following drug-eluting stent placement is associated with long-term adverse outcomes. Occlusion of side branches may be an important factor contributing to periprocedural MIs. Consecutive procedural angiograms of patients randomly assigned to EES (n=669) or PES (n=333) were analysed by an independent angiographic core laboratory. Side branch occlusion was defined as Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 or 1. Clinical outcomes through three years were compared by stent type and presence of side branch occlusion. CONCLUSIONS: A total of 2,048 side branches were evaluated (EES N=1,345 side branches in 688 stented lesions, PES N=703 side branches in 346 stented lesions). Patients with compared to those without transient or final side branch occlusion had significantly higher non-Q-wave MI (NQMI) rates in-hospital (9.0% vs. 0.5%, p<0.0001). By multivariable analysis side branch occlusion was an independent predictor of NQMI (OR 4.45; 95% CI [1.82, 10.85]). Transient or final side branch occlusion occurred less frequently in patients receiving EES compared to PES (2.8% vs. 5.2%, p=0.009), contributing to the numerically lower rates of in-hospital NQMI with EES arm compared to PES (0.7% vs. 2.3%, p=0.05). Patients treated with EES rather than PES were less likely to develop side branch occlusion during stent placement, contributing to lower rates of periprocedural MI with EES compared to PES.