Women treated with the XIENCE V have improved 1-year clinical outcomes compared to women treated with TAXUS; whether benefits in women are sustained at 3 years is unknown. Three-year follow-up of the SPIRIT III trial revealed improved clinical outcomes of the XIENCE V everolimus-eluting stent compared to the TAXUS paclitaxel-eluting stent. One thousand two patients with coronary artery lesions ≤28 mm in length in 2.5- to 3.75-mm diameter vessels were prospectively randomized to receive XIENCE V or TAXUS stents. A post hoc gender subset analysis was performed. Six hundred sixty-nine patients (30% women) received XIENCE V and 332 patients (34% women) received TAXUS. In the overall population, women had higher 3-year rates of major adverse cardiac events (16.0% vs 10.0%, p = 0.01) and target lesion revascularization (10.2% vs 5.3%, p = 0.008) compared to men. In women, those with XIENCE V continued to have lower major adverse cardiac event rates than those with TAXUS at 2 years (9.5% vs 18.3%, p = 0.03) and 3 years (12.2% vs 22.6%, p = 0.03). Although 1-year target vessel failure rates were similar, at 2- and 3-year follow-up women treated with XIENCE V had approximately 40% relative decreases in target vessel failure rates compared to those treated with TAXUS (12.7% vs 22.0%, p = 0.05; 16.0% vs 26.4%, p = 0.03, respectively). Stent thrombosis and bleeding complication rates were similar between treatment arms in the gender subgroups through 3 years. In conclusion, women in the SPIRIT III trial have sustained clinical benefits from XIENCE V implantation compared to TAXUS without increases in long-term complications.
Women develop coronary artery disease nearly a decade later in life than men, and some studies have shown increased rates of restenosis and revascularization after percutaneous coronary interventions in women. Thus, it is unclear whether coronary artery disease progression and responses to therapies are similar between men and women. Recent studies have shown improved outcomes in women treated with drug-eluting stents (DESs) ; however, few have looked at the long-term efficacy of DES implantation in women. Furthermore, given concerns regarding late and very late stent thrombosis, long-term safety of DESs in women deserves attention. The Clinical Trial of the XIENCE V® Everolimus Eluting Coronary Stent System (SPIRIT III) demonstrated the long-term superiority of the XIENCE V everolimus-eluting stent compared to the TAXUS paclitaxel-eluting stent (see 2009 TCT conference presentation) without the late catch-up effect seen with previous stents (see 2009 TCT conference presentation). We previously reported that the benefits of the XIENCE V stent were applicable to women. However, whether the benefits of XIENCE V implantation over TAXUS stent implantation are sustained in women beyond the first year of follow-up is unknown. This report describes the gender-based clinical outcomes of the SPIRIT III trial up to 3 years of follow-up.
Methods
The SPIRIT III study design, major inclusion and exclusion criteria, end points, definitions, and results have been previously described in detail. In brief, 1,002 patients with 1 de novo coronary artery lesion or 2 de novo coronary artery lesions ≤28 mm in length with reference vessels 2.5 to 3.75 mm, as determined by visual estimation, were prospectively randomized in a single-blind fashion to an everolimus-eluting stent (XIENCE V; Abbott Vascular, Santa Clara, California) or a paclitaxel-eluting stent (TAXUS EXPRESS ; Boston Scientific, Natick, Massachusetts). One patient randomized to the paclitaxel-eluting stent group did not sign an informed consent and therefore was not included in analyses. During randomization, patients were stratified by presence of diabetes, planned 2-vessel treatment, and study site. All baseline and follow-up angiograms were analyzed at an independent core angiographic laboratory by technicians blinded to treatment assignments and clinical outcomes. The SPIRIT III trial was approved by the institutional review board at each participating center, and consecutive eligible patients signed written informed consent.
Clinical follow-up was scheduled for 1 month, 6, 8, and 9 months, and then yearly for 5 years. The primary end point was in-segment late loss at 8-month angiographic follow-up. The coprimary end point was ischemia-driven target vessel failure (TVF) at 9-month follow-up adjudicated by an independent clinical events committee. Other adjudicated clinical end points included cardiac death, myocardial infarction (MI), or ischemia-driven target lesion revascularization (TLR) and major adverse cardiac events (MACEs).
All analyses were performed with an intent-to-treat population in this study. Patients lost to follow-up, in whom no event had occurred before the follow-up windows, were not included in the denominator for calculations of binary end points. Categorical variables were compared by Fisher’s exact test. Continuous variables are presented as mean ± SD and were compared by t test. Time-to-event hazard curves also were constructed using the Kaplan–Meier method and compared by log-rank test. All p values calculated were 2-sided. A p value ≤0.05 was considered statistically significant. All statistical analyses were performed using SAS 9.1.3 (SAS Institute, Cary, North Carolina).
Results
Of the 1,001 randomized patients, 669 were assigned to the everolimus-eluting stent (30% women) and 332 were assigned to the paclitaxel-eluting stent (34% women). A patient flow chart based on gender distribution and loss to follow-up is presented in Figure 1 . Baseline clinical and angiographic characteristics according to gender and treatment have been described in detail previously. Briefly, although overall women were older, had higher rates of hypertension, diabetes, and insulin-requiring diabetes, they had lower rates of previous MI and previous cardiac interventions. Furthermore, woman had smaller vessel diameters and lower percent diameter stenosis than men. Number of stents per patient (1.3 ± 0.6 vs 1.3 ± 0.5, p = 0.08) and stent length per lesion (1.60 ± 0.56 vs 1.61 ± 0.45 mm, p = 0.084) were similar between men and women; however, maximum stent diameter per lesion was significantly larger in men than in women (3.06 ± 0.38 vs 2.94 ± 0.36 mm, p <0.0001). Stent treatment groups according to gender were well matched clinically and angiographically ( Table 1 ).
| Variables | Men | Women | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|
| XIENCE V (n = 469) | TAXUS (n = 218) | p Value ⁎ | XIENCE V (n = 200) | TAXUS (n = 114) | p Value | Men (n = 687) | Women (n = 314) | p Value | |
| Demographic features | |||||||||
| Age (years) | 61.92 ± 10.26 | 61.59 ± 9.82 | 0.68 | 66.28 ± 10.56 | 65.12 ± 10.66 | 0.35 | 61.82 ± 10.11 | 65.86 ± 10.60 | <0.0001 |
| Body mass index (kg/m 2 ) | 30.17 ± 5.45 | 30.31 ± 5.35 | 0.76 | 31.34 ± 6.80 | 31.14 ± 6.90 | 0.81 | 30.21 ± 5.42 | 31.27 ± 6.83 | 0.02 |
| Hypertension | 73.3% | 71.4% | 0.64 | 83.0% | 78.9% | 0.37 | 72.7% | 81.5% | 0.003 |
| Hypercholesterolemia | 75.3% | 69.9% | 0.16 | 71.7% | 74.5% | 0.69 | 73.6% | 72.7% | 0.82 |
| All diabetes mellitus | 26.9% | 23.1% | 0.35 | 36.0% | 36.8% | 0.90 | 25.7% | 36.3% | 0.0007 |
| Requiring insulin | 5.3% | 4.2% | 0.58 | 13.5% | 7.9% | 0.15 | 5.0% | 11.5% | 0.0004 |
| Current smoker | 23.7% | 24.5% | 0.85 | 22.6% | 18.8% | 0.47 | 24.0% | 21.2% | 0.37 |
| Previous myocardial infarction | 21.8% | 22.3% | 0.92 | 15.7% | 9.8% | 0.17 | 21.9% | 13.6% | 0.002 |
| Unstable angina | 18.1% | 24.5% | 0.06 | 20.2% | 26.1% | 0.25 | 20.1% | 22.4% | 0.45 |
| Previous cardiac intervention | 35.0% | 32.1% | 0.49 | 26.0% | 24.6% | 0.89 | 34.1% | 25.5% | 0.007 |
| Target lesion characteristics | |||||||||
| Number of lesions | 550 | 254 | 222 | 129 | 804 | 351 | |||
| Coronary artery lesion location | |||||||||
| Left anterior descending | 38.6% | 39.9% | 0.76 | 47.7% | 48.8% | 0.91 | 39.0% | 48.1% | 0.004 |
| Left circumflex | 29.7% | 30.0% | 0.93 | 22.5% | 24.8% | 0.69 | 29.8% | 23.4% | 0.03 |
| Right | 31.5% | 29.6% | 0.62 | 29.7% | 26.4% | 0.54 | 30.9% | 28.5% | 0.44 |
| Left main | 0.2% | 0.4% | 0.53 | 0.0% | 0.0% | — | 0.3% | 0.0% | 1.00 |
| Quantitative coronary angiography | |||||||||
| Reference vessel diameter (mm) | 2.80 ± 0.46 | 2.83 ± 0.46 | 0.31 | 2.69 ± 0.42 | 2.62 ± 0.42 | 0.14 | 2.81 ± 0.46 | 2.67 ± 0.42 | <0.0001 |
| Minimum luminal diameter (mm) | 0.81 ± 0.41 | 0.82 ± 0.40 | 0.79 | 0.85 ± 0.41 | 0.85 ± 0.42 | 0.97 | 0.81 ± 0.41 | 0.85 ± 0.41 | 0.17 |
| Diameter stenosis (%) | 70.68 ± 13.31 | 70.45 ± 13.57 | 0.83 | 68.21 ± 13.27 | 67.47 ± 13.57 | 0.62 | 70.61 ± 13.39 | 67.93 ± 13.36 | 0.002 |
| Lesion length (mm) | 14.92 ± 5.54 | 14.85 ± 5.96 | 0.87 | 14.15 ± 5.68 | 14.51 ± 5.16 | 0.55 | 14.90 ± 5.67 | 14.28 ± 5.49 | 0.08 |
⁎ From post hoc analysis unadjusted for multiple comparison and for descriptive purpose only.
Clinical outcomes at 1-, 2-, and 3-year follow-ups are presented in Table 2 . Overall, women had higher MACE and TLR rates than men throughout the 3-year follow-up period. Although 1-year TVF rates were higher in women compared to men overall, by 3 years TVF was equivalent between men and women. Women treated with TAXUS stents had significantly higher 3-year MACE (p = 0.04) and TVF (p = 0.05) rates than men treated with TAXUS stents, whereas women and men treated with XIENCE V stents had similar 3-year MACE (p = 0.19) and TVF (p = 0.46) rates. Three-year outcomes did not differ between men and women with 1- or 2-vessel disease.
| Variables | Men | Women | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|
| XIENCE V (n = 469) | TAXUS (n = 218) | p Value ⁎ | XIENCE V (n = 200) | TAXUS (n = 114) | p Value ⁎ | Men (n = 687) | Women (n = 314) | p Value ⁎ | |
| 1 year | |||||||||
| Major adverse cardiac events † | 5.0% | 7.2% | 0.28 | 8.2% | 16.1% | 0.04 | 5.7% | 11.0% | 0.005 |
| Target vessel failure † | 7.4% | 8.2% | 0.75 | 11.2% | 17.9% | 0.12 | 7.7% | 13.6% | 0.005 |
| Myocardial infarction ‡ | 2.6% | 2.4% | 1.00 | 3.1% | 7.1% | 0.15 | 2.6% | 4.5% | 0.12 |
| Target lesion revascularization ‡ | 2.2% | 3.9% | 0.30 | 6.1% | 8.9% | 0.37 | 2.7% | 7.1% | 0.003 |
| Cardiac death ‡ | 0.9% | 1.4% | 0.68 | 0.5% | 0.0% | 1.00 | 1.1% | 0.3% | 0.45 |
| Target vessel revascularization, nontarget lesion ‡ | 3.1% | 2.4% | 0.80 | 3.6% | 8.9% | 0.07 | 2.9% | 5.5% | 0.05 |
| Revascularization ‡ § | 4.8% | 4.8% | 1.00 | 9.2% | 13.4% | 0.26 | 4.8% | 10.7% | 0.0009 |
| Bleeding complications ‡ | 2.0% | 3.4% | 0.28 | 6.2% | 9.0% | 0.37 | 2.4% | 7.2% | 0.001 |
| 2 years | |||||||||
| Major adverse cardiac events † | 7.4% | 12.0% | 0.07 | 9.5% | 18.3% | 0.03 | 8.8% | 12.8% | 0.06 |
| Target vessel failure † | 11.2% | 14.5% | 0.24 | 12.7% | 22.0% | 0.05 | 12.2% | 16.1% | 0.10 |
| Myocardial infarction ‡ | 3.3% | 4.5% | 0.50 | 3.2% | 8.3% | 0.10% | 3.7% | 5.0% | 0.38 |
| Target lesion revascularization ‡ | 4.0% | 6.5% | 0.23 | 6.9% | 10.1% | 0.38 | 4.8% | 8.1% | 0.05 |
| Cardiac death ‡ | 1.1% | 2.0% | 0.47 | 1.1% | 0.9% | 1.00 | 1.4% | 1.0% | 0.76 |
| Target vessel revascularization, nontarget lesion ‡ | 5.6% | 5.0% | 0.85 | 4.2% | 11.0% | 0.03 | 5.4% | 6.7% | 0.46 |
| Revascularization ‡ § | 8.7% | 9.5% | 0.77 | 10.1% | 16.5% | 0.14 | 9.0% | 12.4% | 0.10 |
| Bleeding complications ‡ | 2.9% | 5.1% | 0.18 | 6.5% | 10.3% | 0.26 | 3.6% | 7.8% | 0.008 |
| 3 years | |||||||||
| Major adverse cardiac events † | 8.6% | 13.1% | 0.09 | 12.2% | 22.6% | 0.03 | 10.0% | 16.0% | 0.01 |
| Target vessel failure † | 13.6% | 16.6% | 0.33 | 16.0% | 26.4% | 0.03 | 14.5% | 19.7% | 0.06 |
| Myocardial infarction ‡ | 3.9% | 5.0% | 0.53 | 3.7% | 9.4% | 0.07 | 4.2% | 5.8% | 0.32 |
| Target lesion revascularization ‡ | 4.5% | 7.0% | 0.19 | 8.5% | 13.2% | 0.23 | 5.3% | 10.2% | 0.008 |
| Cardiac death ‡ | 1.6% | 2.5% | 0.53 | 1.6% | 0.9% | 1.00 | 1.9% | 1.4% | 0.79 |
| Target vessel revascularization, nontarget lesion ‡ | 7.3% | 6.5% | 0.87 | 5.3% | 13.2% | 0.03 | 7.0% | 8.2% | 0.59 |
| Revascularization ‡ § | 10.4% | 11.6% | 0.68 | 12.8% | 20.8% | 0.09 | 10.8% | 15.6% | 0.04 |
| Bleeding complications ‡ | 3.0% | 5.1% | 0.25 | 7.6% | 10.5% | 0.39 | 3.7% | 8.6% | 0.002 |
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