Influence of Sex on Long-Term Outcomes After Implantation of Bare-Metal Stent: A Multicenter Report From the Coronary Revascularization Demonstrating Outcome Study-Kyoto (CREDO-Kyoto) Registry Cohort-1.

BACKGROUND: Female sex was reported to be associated with lower risk for midterm restenosis and repeat revascularization after bare-metal stent implantation. However, the influence of sex on very long-term outcomes after bare-metal stent implantation has not been yet reported. METHODS AND RESULTS: Among the 9877 patients in the multicenter Coronary Revascularization Demonstrating Outcome study in Kyoto (CREDO-Kyoto) registry cohort-1, bare-metal stent implantation was performed in 5313 patients (men, n=3742 and women, n=1571). Follow-up was completed in 4515 patients (85.0%) at 10 years (duration, 10.3 ± 3.1 [0.0-14.1] years). The cumulative incidence of target-lesion revascularization (TLR) was 27% at 1 year and 34% at 10 years (0.8%/y beyond 1 year). Non-target-lesion revascularization (non-TLR) was the dominant coronary revascularization beyond 1 year (13% at 1 year and 31% at 10 years [2.0%/y beyond 1 year]). Cumulative incidence of stent thrombosis was low (1.2% at 1 year and 1.9% at 10 years). Women were older and had greater prevalence of cardiovascular risk factors than men. The cumulative 10-year incidences of and adjusted risk for TLR were significantly higher in men than in women (36% versus 30%, P<0.001; adjusted hazard ratio, 1.29; 95% confidence interval, 1.15-1.46; P<0.001). The higher risk of men relative to women for TLR was consistent regardless of age (<75 years and ≥ 75 years). Men in comparison with women were also associated with significantly higher adjusted risks for all-cause death, myocardial infarction, stroke, coronary artery bypass grafting, TLR, and non-TLR. CONCLUSIONS: TLR and stent thrombosis continued to occur without attenuation up to 10 years after bare-metal stent implantation. Men in comparison with women were associated with higher adjusted 10-year risks for all-cause death, myocardial infarction, stroke, coronary artery bypass grafting, TLR, and non-TLR.

Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 levels are elevated in acute coronary syndrome: a novel marker for early diagnosis.

BACKGROUND: Markers of cardiac injury, including troponin-T (TnT), are used to diagnose acute coronary syndrome (ACS); however, markers for plaque instability may be more useful for diagnosing ACS at the earliest stage. Lectin-like oxidized LDL receptor-1 (LOX-1) appears to play crucial roles in the pathogenesis of atherosclerotic plaque rupture and ACS onset. LOX-1 is released in part as soluble LOX-1 (sLOX-1) by proteolytic cleavage. METHODS AND RESULTS: We examined serum sLOX-1 levels in 521 patients, consisting of 427 consecutive patients undergoing coronary angiography, including 80 ACS patients, 173 symptomatic coronary heart disease patients, 122 patients with significant coronary stenosis without ischemia, and 52 patients without apparent coronary atherosclerosis plus 34 patients with noncardiac acute illness and 60 patients with noncardiac chronic illness. Time-dependent changes in sLOX-1 and TnT levels were analyzed in an additional 40 ACS patients. Serum sLOX-1 levels were significantly higher in ACS than the other groups and were associated with ACS as shown by multivariable logistic regression analyses. Given a cutoff value of 1.0 ng/mL, sLOX-1 can discriminate ACS from other groups with 81% and 75% of sensitivity and specificity, respectively. sLOX-1 can also discriminate ACS without ST elevation or abnormal Q waves and ACS without TnT elevation from non-ACS with 91% and 83% of sensitivity, respectively. Peak values of sLOX-1 in ACS were observed earlier than those of TnT. CONCLUSIONS: sLOX-1 appears to be a useful marker for early diagnosis of ACS.

Antiplatelet therapy discontinuation and the risk of serious cardiovascular events after coronary stenting: observations from the CREDO-Kyoto Registry Cohort-2.

Relation of antiplatelet therapy (APT) discontinuation with the risk of serious cardiovascular events has not been fully addressed yet. This study is aimed to evaluate the risk of ischemic event after APT discontinuation based on long-term APT status of large cohort. In the CREDO-Kyoto Registry Cohort-2 enrolling 15939 consecutive patients undergoing first coronary revascularization, 10470 patients underwent percutaneous coronary intervention either with bare-metal stents (BMS) only (N=5392) or sirolimus-eluting stents (SES) only (N=5078). Proportions of patients taking dual-APT were 67.3% versus 33.4% at 1-year, and 48.7% versus 24.3% at 5-year in the SES and BMS strata, respectively. We evaluated daily APT status (dual-, single- and no-APT) and linked the adverse events to the APT status just 1-day before the events. No-APT as compared with dual- or single-APT was associated with significantly higher risk for stent thrombosis (ST) beyond 1-month after SES implantation (cumulative incidence rates beyond 1-month: 1.23 versus 0.15/0.29, P<0.001/P<0.001), while higher risk of no-APT for ST was evident only until 6-month after BMS implantation (incidence rates between 1- and 6-month: 8.43 versus 0.71/1.20, P<0.001/P<0.001, and cumulative incidence rates beyond 6-month: 0.31 versus 0.11/0.08, P=0.16/P=0.08). No-APT as compared with dual- or single-APT was also associated with significantly higher risk for spontaneous myocardial infarction (MI) and stroke regardless of the types of stents implanted. Single-APT as compared with dual-APT was not associated with higher risk for serious adverse events, except for the marginally higher risk for ST in the SES stratum. In conclusion, discontinuation of both aspirin and thienopyridines was associated with increased risk for serious cardiovascular events including ST, spontaneous MI and stroke beyond 1-month after coronary stenting.

Late adverse events after implantation of sirolimus-eluting stent and bare-metal stent: long-term (5-7 years) follow-up of the Coronary Revascularization Demonstrating Outcome study-Kyoto registry Cohort-2.

BACKGROUND: Late adverse events such as very late stent thrombosis (VLST) or late target-lesion revascularization (TLR) after first-generation sirolimus-eluting stents (SES) implantation have not been yet fully characterized at long term in comparison with those after bare-metal stent (BMS) implantation. METHODS AND RESULTS: Among 13 058 consecutive patients undergoing first percutaneous coronary intervention in the Coronary REvascularization Demonstrating Outcome study-Kyoto registry Cohort-2, 5078 patients were treated with SES only, and 5392 patients were treated with BMS only. During 7-year follow-up, VLST and late TLR beyond 1 year after SES implantation occurred constantly and without attenuation at 0.24% per year and at 2.0% per year, respectively. Cumulative 7-year incidence of VLST was significantly higher in the SES group than that in the BMS group (1.43% versus 0.68%, P<0.0001). However, there was no excess of all-cause death beyond 1 year in the SES group as compared with that in the BMS group (20.8% versus 19.6%, P=0.91). Cumulative incidences of late TLR (both overall and clinically driven) were also significantly higher in the SES group than in the BMS group (12.0% versus 4.1%, P<0.0001 and 8.5% versus 2.6%, P<0.0001, respectively), leading to late catch-up of the SES group to the BMS group regarding TLR through the entire 7-year follow-up (18.8% versus 25.2%, and 10.6% versus 10.2%, respectively). Clinical presentation as acute coronary syndrome was more common at the time of late SES TLR compared with early SES TLR (21.2% and 10.0%). CONCLUSIONS: Late catch-up phenomenon regarding stent thrombosis and TLR was significantly more pronounced with SES than that with BMS. This limitation should remain the target for improvements of DES technology.

What causes international variations in length of stay: a comparative analysis for two inpatient conditions in Japanese and Canadian hospitals.

Hospital average length of stay varies considerably between countries. However, there is limited patient-level research identifying or discounting possible reasons for these differences. This study compares the length of stay of patients in Japan, where it is the longest in the OECD, and Canada, where length of stay is closer to the OECD mean. Administrative patient-level data, including age, gender, co-morbidities, intervention, discharge plan, outcome and length of stay were collected from two Japanese and two Ontario, Canada hospitals for two diagnoses: colorectal cancer surgery and acute myocardial infarction. Analyses examined linkages between patient characteristics, hospitals and countries and length of stay. When controlling for patient demographic characteristics, the incidence of co-morbidities and discharge plan practices, Japanese length of stay tended to be significantly longer than that in Canada for both diagnoses. Mortality rates were not significantly different; however, the readmission rate (28 days or less) for acute myocardial infarction was higher in the Canadian hospitals. The findings indicate that non-clinical factors contribute to sustained international differences in length of stay. These factors may include professional or cultural norms, differing payment schemes and access to long-term care facilities. The study also introduces a protocol that can be used for international patient-level comparisons that can enable effective policy and management learning.

Long-term safety and efficacy of sirolimus-eluting stents versus bare-metal stents in real world clinical practice in Japan.

Long-term safety and efficacy of drug-eluting stents remains controversial. The CREDO-Kyoto registry cohort-2 is a physician-initiated non-company sponsored multi-center registry enrolling consecutive patients undergoing first coronary revascularization in 26 centers in Japan. We compared 3-year outcome between patients treated with sirolimus-eluting stent (SES) only (5092 patients) and bare-metal stent (BMS) only (5405 patients). SES-use as compared with BMS-use was associated with significantly lower adjusted risk for all-cause death [hazard ratio (HR) [95% confidence interval (CI)] 0.72 (0.59-0.87), P = 0.0007], which was mainly driven by the reduction in non-cardiac death [HR (95% CI) 0.64 (0.48-0.85), P = 0.002]. The risk of cardiac death [HR (95% CI) 0.82 (0.63-1.07), P = 0.15], myocardial infarction [HR (95% CI) 0.73 (0.51-1.03), P = 0.07] and definite stent thrombosis [HR (95% CI) 0.62 (0.35-1.09), P = 0.1] was not different between the two groups. Despite longer duration of thienopyridine administration, SES-use was associated with significantly lower risk for bleeding [HR (95% CI) 0.75 (0.6-0.95), P = 0.02] and similar risk for stroke [HR (95% CI) 1.0 (0.75-1.34), P = 1.0]. The risk for target-lesion revascularization (TLR) was markedly lower in the SES group [HR (95% CI) 0.42 (0.36-0.48), P < 0.0001]. The direction and magnitude of the effect of SES relative to BMS in patients presenting acute myocardial infarction (AMI) were similar to those in patients presenting otherwise. In conclusion, SES-use as compared with BMS-use was associated with marked reduction of TLR without any increases in death, myocardial infarction, stent thrombosis, stroke and bleeding in real world clinical practice regardless of clinical presentation including AMI.

Association of the use of proton pump inhibitors with adverse cardiovascular and bleeding outcomes after percutaneous coronary intervention in the Japanese real world clinical practice.

Previous studies have shown inconsistent results regarding the effects of concomitant use of clopidogrel and proton pump inhibitors (PPI) on cardiovascular outcomes. We sought to evaluate the clinical impact of PPI-use in patients treated with thienopyridines after percutaneous coronary intervention (PCI) in a large Japanese observational database. Among 12446 patients discharged alive on thienopyridines (ticlopidine 90.4% and clopidogrel 9.6%), 3223 patients were treated with PPIs and 9223 patients without PPI at the time of hospital discharge. The PPI group included more patients with co-morbidities than the non-PPI group. The adjusted hazard ratio (HR) of PPI-use for a composite of cardiovascular death, myocardial infarction, and stroke was 1.26 (95% confidence interval (CI) 1.09-1.47, p = 0.002). The adjusted HR of PPI-use for bleeding was 1.26 (95% CI 1.05-1.52, p = 0.013). Cardiovascular and bleeding outcomes were not different among the three groups receiving three different types of PPI. The negative effect of PPI on cardiovascular outcome was consistently seen in both drug-eluting stent (DES) [HR 1.31 (95% CI 1.07-1.6, p = 0.0097)] and non-DES strata [HR 1.25 (95% CI: 0.99-1.57, p = 0.057)] (Interaction p = 0.79) despite the fact that the duration of thienopyridine administration was significantly longer in patients receiving DES. In conclusion, cardiovascular outcomes after PCI were significantly worse in patients with PPI than in patients without PPI in the Japanese real clinical practice. However, the observed poorer cardiovascular outcome in patients receiving PPI was most likely to be related to residual confounding and seemed not causally related to attenuation of antiplatelet effect of thienopyridine through interaction with PPI.

Gender differences in patients with coronary artery disease in Japan: the Japanese Coronary Artery Disease Study (the JCAD study).

BACKGROUND: Gender differences among patients with coronary artery disease vary from study to study. In one of the largest studies, the Japanese Coronary Artery Disease (JCAD) Study, gender differences in patients were investigated. METHODS AND RESULTS: Consecutive patients diagnosed with stenosis 75% or more in at least one branch of the coronary arteries were enrolled in the study. The endpoint is a composite of all-cause death and cardiovascular events. Data were collected over the internet. Out of 15,628 patients screened, 13,812 of them met the inclusion criteria and were followed up for a mean period of 2.7 years. The event rate was 62.8 per 1,000 patients-year, all-cause death 17.3 and total cardiac events 47.4. The incident rate of unstable angina was higher in females (27.1) than males (21.8) (P=0.0363). The incidence of all-cause death was lower in females than males (16.9 and 17.8, respectively; P=0.0148). Other than gender, hypertension and number of vessel disease contribute to the event of unstable angina, and age, family history, obesity, impaired fasting glycemia, hyperlipidemia, congestive heart failure and number of vessel disease contribute to the all-cause death. CONCLUSIONS: Gender is an independent contributing factor of unstable angina and of all-cause death.

Chlamydia pneumoniae seropositivity predicts the risk of restenosis after percutaneous transluminal coronary angioplasty.

This study was done to evaluate whether anti-Chlamydia pneumoniae seropositivity can be a predictor of restenosis after coronary intervention. Recent studies indicate that latent infection with C. pneumoniae is associated with and could possibly cause atherosclerosis. However, it is unknown whether chronic infection with this microorganism is involved in the mechanism of restenosis after percutaneous transluminal coronary angioplasty. We prospectively studied 78 consecutive patients (90 target lesions) with symptomatic coronary artery disease who underwent successful coronary intervention to a de novo lesion (conventional balloon angioplasty to 31 lesions and stent implantation to 59 lesions). At angioplasty, blood samples were collected to measure the serum level of anti-C. pneumoniae IgG to examine whether seropositive patients were prone to restenosis and whether the seropositivity could predict the risk of restenosis determined by follow-up coronary angiography performed within 6 months after the angioplasty. Restenosis, defined as more than 50% stenosis with an increase of 15% or more in the degree of stenosis from that measured on cineangiograms after angioplasty, developed in 36 of 62 seropositive patients and in 4 of 16 seronegative patients (58% vs 25%, P = 0.025). Lesions in the seropositive patients had a greater mean loss index (mean +/- SD 0.75 +/- 0.45 vs 0.35 +/- 0.41, P < 0.001), which was defined as late loss (luminal diameter reduction at follow-up angiography) divided by acute gain (luminal diameter gain by angioplasty), in late loss (1.07 +/- 0.64mm vs 0.65 +/- 0.79mm, P = 0.019), in percentage of diameter stenosis (57% +/- 20% vs 41% +/- 21%, P = 0.003) and a lesser mean in minimal luminal diameter (1.18 +/- 0.58 mm vs 1.67 +/- 0.63 mm, P = 0.002) at follow-up angiography. In a multivariate logistic regression model, anti-C. pneumoniae IgG seropositivity was a strong independent predictor of restenosis compared to the other risk factors (odds ratio = 6.2, P = 0.01). C. pneumoniae could play an important role in the mechanism of restenosis and evaluation of the IgG seropositivity, and may help to identify patients at high risk for restenosis.