Stent length has been considered an important predictor of adverse events after percutaneous coronary intervention, even with the first-generation drug-eluting stents (DESs). The introduction of newer-generation DES has further reduced the rates of adverse clinical events such as restenosis, myocardial infarction, and stent thrombosis. The aim of this study was to compare the impact of stent length on the long-term clinical outcomes between first- and newer-generation DESs. The effects of stent length (≥32 vs <32 mm) on the clinical outcomes were evaluated in 8,445 patients who underwent percutaneous coronary intervention using either a first-generation DES (sirolimus- and paclitaxel-eluting stents, n = 6,334) or a newer-generation DES (everolimus- and zotarolimus-eluting stents, n = 2,111) from January 2004 to December 2009. The 3-year adverse outcomes (composite of all-cause death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis) were compared using the inverse probability of treatment-weighted method according to the stent length. After adjustment for differences in the baseline risk factors, a stent length of ≥32 mm was significantly associated with higher cumulative rates of target vessel revascularization and stent thrombosis in the patients treated with a first-generation DES (adjusted hazard ratio 1.875, 95% confidence interval 1.531 to 2.297, p <0.001; adjusted hazard ratio 2.964, 95% confidence interval 1.270 to 6.917, p = 0.012), but it was not associated with the clinical outcomes in patients treated with a newer-generation DES. In conclusion, stent length might not be associated with long-term clinical outcomes in newer-generation DES era, whereas stent length might be associated with long-term clinical outcomes in the first-generation DESs.
Drug-eluting stents (DESs) have significantly reduced the incidence of restenosis and the need for repeat revascularization after percutaneous coronary intervention (PCI) compared with bare-metal stents. Full lesion coverage using a longer stent has been regarded as the preferred strategy of PCI. Very late stent thrombosis has been an issue, and restenosis has still occurred after first-generation DES implantation, especially in patients who underwent PCI in longer segments. Newer-generation DESs have been designed to further enhance the safety and efficacy in patients undergoing PCI. The use of a newer-generation DES resulted in a reduction in the need for repeat revascularization, myocardial infarction (MI), and stent thrombosis compared with the first-generation DES. The impact of the stent length on long-term clinical outcomes is not well established in the newer-generation DES era. We hypothesized that the clinical impact of the stent length in patients who underwent DES implantation might be different according to the DES types: a first-generation DES versus a newer-generation DES. To test this hypothesis, we analyzed the association between stent length and adverse clinical outcomes in patients receiving a newer-generation DES compared with patients receiving a first-generation DES.
Methods
The COACT (CathOlic medical center percutAneous Coronary inTervention) registry is a large, prospective, observational registry of the demographic, clinical, and procedural data, including the clinical outcomes, of “all-comer” patients who underwent PCI with DES implantation at any of the 8 affiliated hospitals of the Catholic University of Korea from January 2004 to December 2009. Of the 9,292 patients enrolled in this registry, the present study included 8,445 patients who were treated with homogeneous DESs. We categorized the patients into 2 groups depending on the type of stents used: a first-generation DES (a sirolimus-eluting stent, including Cypher and Cypher Select [Cordis, Warren, New Jersey], or a paclitaxel-eluting stent [PES], including TAXUS Express and TAXUS Liberte [Boston Scientific, Natick, Massachusetts]) or a newer-generation DES (a zotarolimus-eluting stent [ZES], including Endeavor Resolute [Medtronic, Santa Rosa, California], and an everolimus-eluting stent [EES], including Xience V [Abbott Vascular, Santa Clara, California] and Promus [Boston Scientific]). Stent length was subdivided into 2 groups based on the total stent length of the target vessel: ≥32 and <32 mm. Patients who were treated with heterogeneous DESs and had contraindications to aspirin or clopidogrel treatment were excluded.
The clinical and outcome data were collected by independent research personnel. All the outcomes of interest were confirmed by a source document and were centrally adjudicated by a local events committee of Seoul St. Mary’s Hospital, Seoul, Korea, whose members were unaware of the patients’ statuses. Systemic arterial hypertension was defined as a documented history of high blood pressure or treatment with antihypertensive medications. Dyslipidemia was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria. For validation of the complete follow-up data, information on the censored survival data and the causes of death was obtained on July 31, 2013 from the Office of Statistics Korea, using unique identification numbers. The study complied with the Declaration of Helsinki regarding investigations in humans, and written informed consent was obtained from each patient before enrollment. There was no industry involvement in the design, conduct, or analysis of the study. The study protocol was approved by the institutional review board at each participating hospital.
Coronary interventions were performed according to current standard techniques. The choice of treatment strategy, stent type, predilatation, poststenting adjunctive balloon inflation, and use of intravascular ultrasound or glycoprotein IIb/IIIa inhibitors were at the discretion of the operators. The aim of the procedure was to obtain full lesion coverage using ≥1 stents. All patients received a loading dose of 300 mg of aspirin and 300 to 600 mg of clopidogrel, unless these antiplatelet medications had been previously administered. The postprocedural antiplatelet therapy consisted of 100 mg/day of aspirin, indefinitely, and 75 mg/day of clopidogrel, for at least 1 year. During the procedure, anticoagulation was obtained using unfractionated heparin at a dose of 5,000 IU or 70 to 100 IU/kg of body weight, according to the standard protocols.
The primary end point was the composite of major adverse cardiac events (MACE), defined as all-cause death, nonfatal MI, and target vessel revascularization (TVR). Death was defined as death from any cause. MI was defined as an increase in the creatinine kinase-MB isoenzyme or troponin value to ≥2 times the normal upper limit and either symptoms consistent with acute myocardial ischemia or electrocardiographic changes in at least 2 contiguous leads (pathologic Q waves, persistent ST-segment elevation, or ST-segment depression >0.1 mV); we did not include periprocedural MI. TVR was defined as clinically driven percutaneous revascularization or bypass of any segment of the epicardial coronary artery containing the target lesion. Stent thrombosis was the cumulative event rate of combined definite and probable stent thrombosis, according to the Academic Research Consortium criteria. Definite stent thrombosis was defined as the occurrence of an acute coronary syndrome with either angiographic or pathologic confirmation of thrombosis, and probable stent thrombosis was defined as any unexplained death within 30 days or a target vessel MI without angiographic confirmation of thrombosis or other identified culprit lesions. The patients were required to visit the outpatient clinic at the end of the first month every 3 months after the PCI procedure and when angina-like symptoms reoccurred.
The continuous variables are expressed as mean ± SD and were compared using Student t or the Mann-Whitney U test. The categorical variables were compared using the chi-square or Fisher’s exact test. Survival curves were constructed with Kaplan-Meier estimates and compared using the log-rank test. To reduce the impact of treatment selection bias and the potential confounding factors in an observational study, we performed a rigorous adjustment for differences in the baseline characteristics of patients using the weighted Cox proportional hazards regression models with the inverse probability of treatment weighting. With that technique, the weights for patients whose stent length is <32 mm were the inverse of 1-propensity score, and the weights for patients whose stent length is ≥32 mm were the inverse of the propensity score. The propensity scores were estimated without regard for the outcomes using a multiple logistic regression analysis. Adjusted covariates, including age, gender, body mass index, hypertension, diabetes, smoking, dyslipidemia, chronic kidney disease, stroke, family history of coronary artery disease, acute MI, multivessel disease, bifurcation lesion, stent overlap, stent diameter, left ventricular ejection fraction, hemoglobin, HbA1c, estimated glomerular filtration rate, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein, β blocker, calcium channel blocker, angiotensin-converting enzyme inhibitor, and angiotensin receptor blocker, were used for the generation of propensity scores. Model discrimination was assessed using c-statistics, and model calibration was assessed using Hosmer-Lemeshow statistics. For each clinical group, a separate propensity for a first- versus newer-generation DES was derived. All the analyses were 2-tailed, with clinical significance defined as p values <0.05. SAS software, version 9.2 (SAS Institute Inc, Cary, North Carolina), and the R programming language were used for the statistical analyses.
Results
From January 2004 through December 2009, 8,445 patients underwent PCI with a DES (a sirolimus-eluting stent for 4,076 [48%], a PES for 2,258 [27%], an EES for 1,099 [13%], and a ZES for 1,012 [12%]). Among all the patients, the median stent length was 23 mm (interquartile range 18 to 33). In the receiver operating characteristic curve analysis, the optimal cut-off point to predict TVR was stent length >31 mm, with sensitivity 35% and specificity 71%. The patients were categorized into 2 groups: the first-generation DES group (n = 6,334, 75% of total patients; stent length ≥32 mm [2,151, 34%] and <32 mm [4,183, 66%]) and the newer-generation DES group (n = 2,111, 25.0% of total patients; stent length ≥32 mm [378, 18%] and <32 mm [1,733, 82%]). The baseline and angiographic characteristics of the patients are listed in Tables 1 and 2 , respectively. The patients treated with a stent length of ≥32 mm had a greater risk clinical and procedural profile than those treated with a stent length <32 mm.
| Variable | Stent Length (mm) | p Value | |
|---|---|---|---|
| <32, n = 4,183 (%) | ≥32, n = 2,151 (%) | ||
| Age (yrs) | 62.7 ± 11.0 | 63.8 ± 10.5 | 0.0003 |
| Men | 2,679 (64) | 1,350 (63) | 0.315 |
| Body mass index (kg/m 2 ) | 24.6 ± 3.2 | 24.6 ± 3.1 | 0.742 |
| Hypertension | 2,370 (57) | 1,344 (63) | <0.0001 |
| Diabetes mellitus | 1,575 (38) | 809 (38) | 0.974 |
| Smoker | 1,683 (40) | 833 (39) | 0.245 |
| Dyslipidemia | 364 (9) | 233 (11) | 0.008 |
| Chronic kidney disease | 229 (6) | 147 (7) | 0.030 |
| Stroke | 286 (7) | 186 (9) | 0.009 |
| Acute MI | 1,416 (34) | 690 (32) | 0.156 |
| Ejection fraction <40% | 222 (6%) | 171 (9%) | <0.0001 |
| Estimated glomerular filtration rate (ml/min/1.73 m 2 ) | 67.2 ± 31.8 | 64.8 ± 42.2 | 0.020 |
| High-sensitivity C-reactive protein (mg/dl) | 1.2 ± 2.9 | 1.3 ± 3.0 | 0.231 |
| Hemoglobin A1c (%) | 6.5 ± 1.5 | 6.7 ± 1.5 | 0.005 |
| Total cholesterol (mg/dl) | 178.5 ± 41.2 | 177.7 ± 44.7 | 0.512 |
| Triglyceride (mg/dl) | 144.9 ± 106.7 | 146.3 ± 108.3 | 0.646 |
| High-density lipoprotein (mg/dl) | 41.6 ± 10.8 | 41.2 ± 10.7 | 0.108 |
| Low-density lipoprotein (mg/dl) | 108.0 ± 37.9 | 107.3 ± 40.5 | 0.536 |
| Hemoglobin (g/dl) | 13.3 ± 1.9 | 13.2 ± 1.9 | 0.059 |
| Medication during follow-up | |||
| β Blockers | 2,819 (67) | 1,461 (68) | 0.670 |
| Statins | 3,331 (80) | 1,717 (80) | 0.858 |
| Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers | 3,115 (75) | 1,562 (73) | 0.113 |
| Calcium channel blockers | 878 (21.0) | 475 (22) | 0.315 |
| Type B2/C lesion | 2,777 (66) | 1,990 (93) | <0.0001 |
| Bifurcation | 487 (12) | 273 (13) | 0.221 |
| Overlapping | 55 (1) | 942 (44) | <0.0001 |
| Multivessel disease | 2,101 (50) | 1,382 (64) | <0.0001 |
| Number of stent | 1.0 ± 0.1 | 1.4 ± 0.6 | <0.0001 |
| Stent diameter (mm) | 3.19 ± 0.41 | 3.10 ± 0.34 | <0.0001 |
| Stent length (mm) | 21.0 ± 4.6 | 42.4 ± 12.7 | <0.0001 |
| Variable | Stent Length (mm) | p Value | |
|---|---|---|---|
| <32 (n = 1,733) | ≥32 (n = 378) | ||
| Age (yrs) | 64.0 ± 11.6 | 64.4 ± 11.2 | 0.606 |
| Men | 1,079 (62) | 253 (67) | 0.088 |
| Body mass index (kg/m 2 ) | 24.7 ± 3.4 | 24.3 ± 3.1 | 0.066 |
| Hypertension | 1,008 (58) | 230 (61) | 0.338 |
| Diabetes mellitus | 627 (36) | 146 (39) | 0.371 |
| Smoker | 643 (37) | 144 (38) | 0.718 |
| Dyslipidemia | 137 (8) | 30 (9) | 0.945 |
| Chronic kidney disease | 109 (6) | 21 (6) | 0.591 |
| Stroke | 122 (7) | 42 (11) | 0.007 |
| Acute MI | 524 (30) | 126 (33) | 0.237 |
| Ejection fraction <40% | 97 (6) | 30 (9) | 0.098 |
| Estimated glomerular filtration rate (ml/min/1.73 m 2 ) | 68.6 ± 32.8 | 63.8 ± 27.9 | 0.003 |
| High-sensitivity C-reactive protein (mg/dl) | 1.0 ± 2.6 | 1.3 ± 3.6 | 0.145 |
| Hemoglobin A1c (%) | 6.7 ± 1.5 | 7.0 ± 1.5 | 0.007 |
| Total cholesterol (mg/dl) | 174.9 ± 42.4 | 173.1 ± 43.7 | 0.476 |
| Triglyceride (mg/dl) | 148.7 ± 111.8 | 150.9 ± 151.0 | 0.792 |
| High-density lipoprotein (mg/dl) | 43.0 ± 12.1 | 42.0 ± 11.3 | 0.171 |
| Low-density lipoprotein (mg/dl) | 102.3 ± 37.5 | 101.7 ± 38.4 | 0.799 |
| Hemoglobin, g/dl | 13.3 ± 1.9 | 13.2 ± 1.9 | 0.734 |
| Medication during follow-up | |||
| β Blockers | 1,147 (66) | 272 (72) | 0.030 |
| Statins | 1,483 (86) | 325 (86) | 0.839 |
| Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers | 1,265 (73) | 274 (73) | 0.840 |
| Calcium channel blockers | 483 (28) | 87 (23) | 0.054 |
| Type B2/C lesion | 1,142 (66) | 361 (96) | <0.0001 |
| Bifurcation | 196 (11) | 48 (13) | 0.447 |
| Overlapping | 22 (1) | 336 (89) | <0.0001 |
| Multivessel disease | 915 (53) | 257 (68) | <0.0001 |
| Number of stent | 1.1 ± 0.2 | 2.1 ± 0.3 | <0.0001 |
| Stent diameter (mm) | 3.26 ± 0.47 | 3.14 ± 0.35 | <0.0001 |
| Stent length (mm) | 21.1 ± 5.4 | 49.8 ± 12.4 | <0.0001 |
The median follow-up was 36.9 months (interquartile range 22.3 to 51.2) in the patients. During the overall follow-up, 811 patients (10%) died. A total of 79 patients (1%) had a nonfatal MI, and TVR was performed in 884 patients (11%).
The crude and adjusted hazard ratios (HRs), according to the stent length during the 3 years of follow-up, are presented in Table 3 . The cumulative incidences of MACE, all-cause death, nonfatal MI, and TVR of first-generation DES, according to the length of the stents, are presented in Figure 1 . The cumulative incidences of MACE, all-cause death, nonfatal MI, and TVR of newer-generation DESs, according to the length of the stents, are presented in Figure 2 . In separate DES analysis, there was difference of incidence of TVR according to the stent length: sirolimus-eluting stent, <32 versus ≥32 mm, 7% versus 9%, HR 1.27, 95% confidence interval (CI) 1.01 to 1.59, p = 0.038; PES, 9% versus 12%, HR 1.40, 95% CI 1.08 to 1.83, p = 0.012; EES, 5% versus 6%, HR 1.15, 95% CI 0.63 to 2.10, p = 0.647; ZES, 5% versus 7%, HR 1.59, 95% CI 0.79 to 3.17, p = 0.192, respectively.
| Outcome | Stent Length (mm) | Unadjusted | Multivariate Adjusted | Adjusted by Inverse Probability of Treatment Weights | ||||
|---|---|---|---|---|---|---|---|---|
| <32 (%) | ≥32 (%) | HR (95% CI) | p | HR (95% CI) ∗ | p | HR (95% CI) | p | |
| 1st-generation DES | ||||||||
| All-cause death | 250 (6.0) | 147 (6.8) | 1.194 (0.974–1.464) | 0.088 | 1.067 (0.834–1.366) | 0.604 | 1.088 (0.841–1.408) | 0.522 |
| Nonfatal MI | 29 (0.7) | 14 (0.7) | 0.977 (0.516–1.849) | 0.943 | 1.159 (0.562–2.392) | 0.689 | 1.169 (0.546–2.503) | 0.688 |
| TVR | 209 (5.0) | 150 (7.0) | 1.487 (1.206–1.834) | <0.001 | 1.427 (1.144–1.779) | 0.002 | 1.875 (1.531–2.297) | <0.001 |
| MACE | 456 (10.9) | 288 (13.4) | 1.295 (1.117–1.500) | <0.001 | 1.177 (0.984–1.408) | 0.075 | 1.171 (0.972–1.412) | 0.097 |
| Stent thrombosis | 13 (0.3) | 15 (0.7) | 2.308 (1.098–4.851) | 0.027 | 3.210 (1.366–7.545) | 0.008 | 2.964 (1.270–6.917) | 0.012 |
| Newer-generation DES | ||||||||
| All-cause death | 99 (5.7) | 27 (7.1) | 1.278 (0.835–1.956) | 0.259 | 1.911 (0.767–4.765) | 0.165 | 1.673 (0.690–4.057) | 0.255 |
| Nonfatal MI | 10 (0.6) | 4 (1.1) | 1.873 (0.588–5.974) | 0.289 | 0.820 (0.034–19.941) | 0.903 | 1.107 (0.058–21.267) | 0.946 |
| TVR | 62 (3.6) | 15 (4.0) | 1.129 (0.642–1.984) | 0.674 | 1.683 (0.599–4.731) | 0.324 | 2.105 (0.753–5.884) | 0.156 |
| MACE | 165 (9.5) | 41 (10.9) | 1.164 (0.827–1.639) | 0.383 | 1.661 (0.844–3.269) | 0.142 | 1.791 (0.915–3.509) | 0.089 |
| Stent thrombosis | 4 (0.2) | 1 (0.3) | 1.172 (0.131–10.488) | 0.887 | 0.783 (0.004–159.317) | 0.928 | 0.647 (0.003–141.648) | 0.874 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
