Methods

Consecutive Japanese patients who underwent PCI at Juntendo University Hospital (Tokyo, Japan) from January 2004 to October 2011 were considered for this retrospective analysis. Patients with an implanted DES were included in this analysis, whereas those with no stents or bare metal stents (BMSs) were excluded because antiplatelet therapy was changed from dual to single in 3 or 6 months in these patients. During this study period, DAPT was continued for all patients with an implanted DES to prevent stent thrombosis until a bleeding event would occur in our hospital. All patients took DAPT for >2 years unless a bleeding event would occur. Therefore, it was important to be able to predict bleeding events in such patients. The hospital’s internal review board approved this study. Informed consent was obtained from all patients.

Baseline data included age, gender, body mass index, blood pressure (BP), and total cholesterol. Low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, fasting blood glucose at the time of PCI, smoking status, family history of coronary artery disease, medication use, revascularization procedure-related factors, and co-morbidities were prospectively collected from each patient. Blood samples were collected in the early morning after an overnight fast. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥9 0 mm Hg, or treatment with antihypertensive medications. Dyslipidemia was defined as low-density lipoprotein cholesterol >140 mg/dl, high-density lipoprotein cholesterol <40 mg/dl, triglycerides >150 mg/dl, or treatment with lipid-lowering drugs. Diabetes mellitus was defined as a fasting plasma glucose level ≥126 mg/dl or treatment with oral hypoglycemic drugs or insulin injections. A current smoker was defined as one who smoked at the time of PCI or had quit smoking within 1 year before PCI. In all patients, indications for PCI were based on objective evidence of myocardial ischemia (positive stress test), ischemic symptoms, or signs associated with significant angiographic stenosis.

The HAS-BLED score was determined by adding 1 point for each of the following: hypertension, abnormal renal/liver function (1 point for each), stroke, bleeding history or predisposition, labile international normalized ratio, elderly (>65 years), and drugs/alcohol concomitantly (1 point for each one). The patients were then classified into 2 groups based on the HAS-BLED score (high ≥3, low 0 to 2) because several previous studies showed that a score ≥3 was associated with bleeding events in patients with AF.

The follow-up period ended on December 31, 2011. Survival data and data on bleeding events were collected by serial contact with the patients or their families, and they were assessed from the medical records of patients who had died or of those who were followed up at our hospital. Information about the circumstances and date of death were obtained from the families of patients who died at home, and details of events or the cause of death were supplied by other hospitals or clinics where the patients had been admitted. All data were collected by blinded investigators. Major bleeding was defined as type 3 or more of the definition of the Bleeding Academic Consortium.

The results are expressed as mean ± SD or median (interquartile range) for continuous variables and percentages for categorical variables. Baseline data were compared using the unpaired t test or the Mann-Whitney U test for continuous variables and the chi-square test or Fisher’s exact test for categorical variables. Event-free survival curves were drawn using the Kaplan-Meier method, and the log-rank test was used to compare 2 event-free survival curves. To determine factors associated with outcomes, univariate Cox regression analysis was performed first, and the covariate factors with a significant or borderline significant association (p <0.10) with outcomes (except those 7 included in the HAS-BLED score) were then included in multivariate Cox regression analysis. A p value <0.05 was considered significant, unless otherwise indicated. All data were analyzed using JMP 10.0 MDSU statistical software (SAS Institute, Cary, North Carolina).