Association of Second-Generation Drug-Eluting Stent Length With 2-Year Adverse Clinical Outcomes Among Japanese Patients With Ischemic Heart Disease.

Introduction

During the bare-metal or first-generation drug-eluting stent (DES) era, longer stent length was linked with higher incidence of subsequent stent-related complications, such as stent restenosis and stent thrombosis, after percutaneous coronary intervention (PCI).[1,2] However, data exploring this association during the second-generation DES era remain scarce.[3,4] This cohort study investigated the association between total stent length (TSL) of second-generation DES and 2-year clinically driven events, including bleeding events, after index PCI in a contemporary Japanese registry.

Methods

A total of 2399 patients within the Keio Interhospital Cardiovascular Studies (KiCS) PCI Registry who received second-generation DES implantation during PCI and were discharged alive between January 2009 and December 2012 were included in the analysis. The study population was divided and compared among 3 groups according to TSL: short (<32 mm), intermediate (32-50 mm), and long (>50 mm). This study was conducted according to the principles expressed in the Declaration of Helsinki[5] and was approved by the institutional review board of each hospital. All participants provided written informed consent. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies.

The primary outcome was defined as 2-year major adverse cardiovascular and cerebrovascular events (MACCE) after hospital discharge, including all-cause death, nonfatal acute coronary syndrome, hospitalization for heart failure, and nonfatal stroke. The primary safety outcome was bleeding events for 2 years after hospital discharge. Bleeding events were defined as any bleeding event resulting in hospitalization.

Events were estimated in a time-to-event manner using the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HRs) and 95% CIs of TSL for 2-year MACCE were estimated using Cox proportional hazards regression models. Statistical significance was defined as 2-tailed P < .05. All statistical analyses were performed in Stata version 13.1 (StataCorp).

Results

Overall, the median (interquartile range [IQR]) age was 69 (61-76) years and 1870 of 2391 total participants (78.2%) were male. The median (IQR) TSL was 24 (18-38) mm, ranging from 8 to 132 mm (Figure). Median (IQR) TSL in patients with multivessel PCI was significantly longer than in those with single-vessel PCI (44 [33-59] mm vs 24 [18-35] mm; P < .001). At 2 years, long TSL was associated with higher incidence of MACCE and hospitalization for heart failure compared with intermediate or short TSL (MACCE: 45 of 323 patients [13.9%] vs 48 of 427 patients [11.2%] vs 153 of 1649 patients [9.3%]; P = .03; hospitalization for heart failure: 21 of 323 [6.5%] vs 20 of 427 [4.7%] vs 60 of 1649 [3.6%]; P = .047). Similarly, the incidence of bleeding was higher in the long TSL group than that in the intermediate or short TSL groups (15 of 323 [4.6%] vs 8 of 427 [1.9%] vs 34 of 1649 [2.1%]; P = .01) (Table and Figure). After multivariable Cox regression analysis, the HRs of long TSL for 2-year MACCE (HR, 2.30; 95% CI, 1.21-4.38) and bleeding (HR, 2.31; 95% CI, 1.25-4.27; P = .008) were higher than that of short TSL (reference group).

Figure.

Total Stent Length and Cumulative Incidence of Study Outcomes

MACCE indicates major adverse cardiovascular or cerebrovascular event; TSL, total stent length.

Table.

Primary and Safety End Points

End point	Total stent length, No. (%)			P value
	Short, <32 mm (n = 1649)	Intermediate, 32-50 mm (n = 427)	Long, >50 mm (n = 323)
Primary end point
MACCE	153 (9.3)	48 (11.2)	45 (13.9)	.03
All-cause death	51 (3.1)	18 (4.2)	13 (4.0)	.42
CV death	16 (1.0)	6 (1.4)	5 (1.5)	.55
ACS	48 (2.9)	11 (2.6)	6 (1.9)	.57
Hospitalization for heart failure	60 (3.6)	20 (4.7)	21 (6.5)	.047
Stroke	24 (1.5)	6 (1.4)	9 (2.8)	.20
Safety end point
Bleeding	34 (2.1)	8 (1.9)	15 (4.6)	.01

Abbreviations: ACS, acute coronary syndrome; CV, cardiovascular; MACCE, major adverse cardiovascular and cerebrovascular event.

Discussion

In this study, we demonstrated the association of long TSL with increased risk of 2-year MACCE, heart failure hospitalization, and bleeding events after second-generation DES implantation for both sexes, elaborating the findings from the Women in Innovation and Drug-Eluting Stents all-woman pooled database study, in which data were collected from randomized clinical trials.[3] Long TSL (>50 mm) may inadvertently affect normal cardiac function through minimal ischemia because of side-branch obstruction and stent-related microvascular dysfunction, leading to higher incidence of heart failure hospitalization. Giustino et al[6] also found that stent length greater than 60 mm was an independent correlate of thrombotic events after PCI. Furthermore, longer duration of dual antiplatelet therapy for preventing thrombosis in those with long TSL may be associated with the higher incidence of bleeding.

This study has limitations, including an observational research design that potentially would not account for unmeasured confounding factors. We adjusted for known associated factors based on currently clinically available risk scores such as the Dual Antiplatelet Therapy Study score and the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy score. Although a causal relationship cannot be verified through our observational study design, our findings were rigorously adjusted for possible confounders and suggest the continuing importance of minimizing TSL during PCI and of carefully monitoring for heart failure and bleeding after PCI in patients with long TSL.