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.

Regression of Electrocardiographic Signs of Left Ventricular Hypertrophy by Combined Treatment With Thiazide Diuretic and Angiotensin-II Receptor Blocker.

BACKGROUND: In hypertensive patients, left ventricular hypertrophy (LVH) may persist despite satisfactory blood pressure (BP) control. The efficacy of thiazide diuretics in Western countries has been reported, but whether this applies to hypertensive Japanese patients is uncertain. METHODS AND RESULTS: We randomly assigned 94 patients whose BP was poorly controlled with usual doses of angiotensin-II receptor blockers (ARB), to losartan/hydrochlorothiazide (HCTZ) fixed-dose combination vs. maximum doses of ARB. After 6 months follow-up, decrease in BP, regression of electrocardiographic LVH, and changes in laboratory measurements were examined. Although a similar decrease in BP was observed in both groups, the decrease in LV Sokolow-Lyon voltage, from 34.4±9.2 to 29.4±8.8 mm in the losartan/HCTZ vs. from 29.9±10.2 to 29.1±8.4 mm in the ARB group (P=0.0003), and the decrease in serum B-type natriuretic peptide (BNP) level, from 30.1±28.5 to 26.8±28.0 pg/ml vs. from 23.7±14.8 to 29.8±29.3 pg/ml (P=0.045) were greater in the losartan/HCTZ group. By single variable logistic regression analysis, ∆BNP (P=0.012) and treatment with losartan/HCTZ (P<0.0001) correlated with the regression of LVH. By multiple variable logistic regression analysis, both ∆BNP (P=0.035) and treatment with losartan/HCTZ (P=0.0003) remained significant. No major adverse effects were observed. CONCLUSIONS: Greater regression of LVH was safely achieved with losartan/HCTZ in patients whose BP was poorly controlled with an ARB.

Comparison of everolimus-eluting and sirolimus-eluting coronary stents: 1-year outcomes from the Randomized Evaluation of Sirolimus-eluting Versus Everolimus-eluting stent Trial (RESET).

BACKGROUND: Several recent randomized trials comparing everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) reported similar outcomes. However, only 1 trial was powered for a clinical end point, and no trial was powered for evaluating target-lesion revascularization. METHODS AND RESULTS: Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial is a prospective multicenter randomized open-label trial comparing EES with SES in Japan. The trial was powered for evaluating noninferiority of EES relative to SES in terms of target-lesion revascularization. From February and July 2010, 3197 patients were randomly assigned to receive either EES (1597 patients) or SES (1600 patients). At 1 year, the primary efficacy end point of target-lesion revascularization occurred in 65 patients (4.3%) in the EES group and in 76 patients (5.0%) in the SES group, demonstrating noninferiority of EES to SES (P(noninferiority)<0.0001, and P(superiority)=0.34). Cumulative incidence of definite stent thrombosis was low and similar between the 2 groups (0.32% versus 0.38%, P=0.77). An angiographic substudy enrolling 571 patients (EES, 285 patients and SES, 286 patients) demonstrated noninferiority of EES relative to SES regarding the primary angiographic end point of in-segment late loss (0.06±0.37 mm versus 0.02±0.46 mm, P(noninferiority)<0.0001, and P(superiority)=0.24) at 278±63 days after index stent implantation. CONCLUSIONS: One-year clinical and angiographic outcome after EES implantation was noninferior to and not different from that after SES implantation in a stable coronary artery disease population with relatively less complex coronary anatomy. One-year clinical outcome after both EES and SES use was excellent with a low rate of target-lesion revascularization and a very low rate of stent thrombosis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035450.

Correlation between serum concentrations of B-type natriuretic peptide and albumin in patients with chronic congestive heart failure.

While B-type natriuretic peptide (BNP) and hypoalbuminemia are both predictors of major adverse cardiac events (MACE) in patients with congestive heart failure (CHF), whether these markers are correlated is not known. We retrospectively analyzed data collected in 85 patients presenting with CHF, a left ventricular (LV) ejection fraction (EF) < 50%, and non-ischemic heart disease, followed for a mean of 38 months. Statistical analysis was performed to 1) examine the relationship between a) baseline BNP or albumin concentrations and b) baseline clinical characteristics, 2) identify the correlates of changes in (Δ) BNP concentrations, and Δ albumin concentrations, and 3) ascertain the prognostic value of each variable. Log transformed BNP was correlated with New York Heart Association functional class, total protein and LVEF, while albumin was correlated with a history of diabetes mellitus and total protein. Δ BNP and Δ albumin concentrations between baseline and follow-up were correlated (P < 0.0001). The follow-up BNP and albumin concentrations were independent predictors of MACE.BNP and albumin were correlated with different baseline clinical characteristics. The long-term changes in the two markers were inversely correlated and both were independent predictors of CHF.

Correlates of NT-proBNP concentration in patients with essential hypertension in absence of congestive heart failure.

BACKGROUND: N-terminal proBNP (NT-proBNP) is widely used as a diagnostic biomarker and for the risk stratification of patients with heart failure (HF). Its role in the evaluation of patients with essential hypertension (EHT) is less clear. We examined the relationship between NT-proBNP concentrations and various clinical characteristics in hypertensive patients without HF. METHODS: This study included 186 consecutive patients with EHT and no history of HF, ischemic heart disease, or atrial fibrillation. Single and multiple variable regression analyses were performed in search of clinical correlates of NT-proBNP concentrations. RESULTS: In patients with EHT, median serum concentration of NT-proBNP was 73 pg/ml, and interquartile range (IQR) was 40-128 pg/ml. NT-proBNP was significantly higher (P<0.001) in women (87 pg/ml; IQR 55-137 pg/ml) than in men (52 pg/ml; IQR 24-115 pg/ml). Age (r=0.371, P<0.001), precordial QRS voltage (r=0.223, P<0.001), hemoglobin (Hgb) concentration, (r=-0.208, P=0.023) and estimated glomerular filtration rate (r=-0.139, P=0.044) were correlated with log-transformed NT-proBNP by multiple variable analysis. In men, age (r=0.453, P<0.001) and QRS voltage (r=0.283, P=0.004), and in women age (r=0.299, P=0.006), QRS voltage (r=0.212, P=0.019), Hgb (r=-0.182, P=0.049), and estimated glomerular filtration rate (r=-0.272, P=0.009) were correlated with serum concentrations of NT-proBNP. CONCLUSIONS: Age, gender, Hgb, left ventricular hypertrophy and renal function were correlated with NT-proBNP in patients with EHT.

Mortality impact of post-discharge myocardial infarction size after percutaneous coronary intervention: a patient-level pooled analysis from the 4 large-scale Japanese studies.

It is unknown whether there is a threshold of creatine kinase (CK) or CK-MB affecting the subsequent mortality for post-discharge myocardial infarction (PDMI) after percutaneous coronary intervention. Current study sought to evaluate the impact of PDMI. The study population included 30,051 patients with successful coronary stenting and discharged alive in the pooled patient-level database of 4 Japanese studies (j-Cypher registry, CREDO-Kyoto PCI/CABG registry cohort-2, RESET, and NEXT). During 4.4 ± 1.4 year follow-up, 915 patients experienced PDMI (cumulative 5-year incidence of 3.6%). Among 466 patients with available peak CK ratio (peak CK/upper limit of normal), peak CK ratio (< 3) was present in 21% of patients, while peak CK ratios (≥ 3 and < 5), (≥ 5 and < 10), (≥ 10 and < 30), and (≥ 30) were present in 17, 25, 30, and 7.3% of patients, respectively. The excess mortality risk of patients with relative to those without PDMI for subsequent mortality was significant (adjusted HR 5.12, 95% CI 4.52-5.80, P < 0.001) by the Cox model with PDMI incorporated as the time-updated covariate. However, the mortality risk of patients in the smallest peak CK ratio category (< 3) was insignificant (HR 0.85, 95% CI 0.43-1.71, P = 0.65). In conclusion, despite significant overall mortality risk of PDMI, the mortality risk of small PDMI was similar to that of no PDMI, suggesting the presence of some threshold about infarct size influencing mortality.Trial registrations The Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial (RESET); NCT01035450 and NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial (NEXT); NCT01303640. J-Cypher and CREDO-Kyoto PCI/CABG registry cohort 2 were not registered into clinical trial database.

The deeper the pouch is, the longer the radiofrequency duration and higher the radiofrequency energy needed-Cavotricuspid isthmus ablation using intracardiac echocardiography.

BACKGROUND: The aim of this study was to explore whether the pouch depth influenced the radiofrequency (RF) duration and total delivered RF energy for cavotricuspid isthmus (CTI) ablation and define the cutoff value for a deep pouch-specified ablation strategy. METHODS: This study included 94 atrial fibrillation (AF) patients (56 males, age 68 ± 8.0 years). With intracardiac echocardiography, the isthmus length and pouch depth were precisely measured. After a standard AF ablation, all patients underwent the CTI ablation along the lateral isthmus. If bidirectional block could not be achieved, the ablation catheter was deflected more than 90 degrees to ablate inside the pouch (knuckle-curve ablation). RESULTS: Seventy-two patients (76.6%) had a sub-Eustachian pouch. Bidirectional block could be achieved in all patients. By a univariate logistic regression analysis, only the pouch depth was significantly correlated with the RF duration (P = .005) and RF energy (P = .006). A multivariate logistic regression analysis also revealed the pouch depth was the sole factor that influenced the RF duration (P = .001) and RF energy (P = .001). Among the 72 patients, 21 patients needed a knuckle-curve ablation. Using a receiver operating characteristic curve, the optimal cutoff value of the pouch depth for a knuckle-curve ablation was 3.7 mm with a sensitivity of 90% and specificity of 69%. CONCLUSIONS: The sub-Eustachian pouch depth was the sole factor that influenced the RF duration and energy in the CTI ablation. If the pouch was deeper than 3.7 mm, a deep pouch-specified ablation strategy would be needed.

Ultrastructural aspects of vacuolar degeneration of cardiomyocytes in human endomyocardial biopsies.

Vacuolar degeneration of cardiomyocytes is a histological finding commonly encountered during routine light microscopic examination of human endomyocardial biopsy specimens. The vacuoles appear as intracellular clear areas lacking myofibers. By itself, this finding has little diagnostic value, but may have important clinical implications when the vacuolar contents are of etiological significance (e.g., accumulation of abnormal metabolites), and the clinical importance is increased when the disease is treatable. Thanks to its great resolving power, electron microscopy can often reveal the contents of the vacuoles and lead to a correct diagnosis. It can be used to differentially diagnose lysosomal storage diseases such as Fabry, Danon, and Pompe disease, doxorubicin cardiomyopathy, mitochondrial cardiomyopathy, autophagic degeneration, and accumulation of subcellular organelles (mitochondria, lipofuscin, glycogen granules, endoplasmic reticulum, etc.) as a nonspecific finding in failing cardiomyocytes. Nonetheless, undiagnosed cases certainly remain. It is strongly recommended that small pieces of tissue samples be fixed for electron microscopy at every endomyocardial biopsy procedure, and electron microscopic examination should be performed when a marked vacuolar degeneration is found.

Prognostic significance of changes in cystatin C during treatment of acute cardiac decompensation.

BACKGROUND: The long-term prognostic significance of in-hospital worsening renal function (WRF) during treatment of acute cardiac decompensation (ACD) remains controversial. METHODS: We analyzed data from 100 patients (mean age=75 years; 53% men) presenting with ACD, in whom the serum cystatin C (Cys-C) concentration was measured upon admission to the hospital and 4 days later. We examined the relationship between changes in Cys-C and primary study endpoint of risk of death and re-hospitalization for management of ACD, up to 180 days, searched for predictors by multiple variable analysis and calculated the hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: A median (25th to 75th percentile) increase in Cys-C from 1.29 (0.88-1.66)mg/l on day 1 to 1.31 (1.00-1.84)mg/l on day 4, observed in 66% of all patients, was associated with a significant decrease (p=0.040) in the 180-day incidence of primary study endpoint. By multiple variable regression analysis, an increase in Cys-C was an independent predictor of death and re-hospitalization for management of ACD (HR 0.415; 95% CI 0.193-0.885; p=0.023). CONCLUSIONS: An increase in serum Cys-C concentration after hospitalization for management of ACD was associated with a decreased, long-term incidence of primary study endpoint.

Prognostic Value of Rising Serum Albumin During Hospitalization in Patients With Acute Heart Failure.

Hypoalbuminemia is an important predictor of a poor long-term prognosis in acute heart failure (AHF). However, changes in serum albumin levels in AHF have not been described to date. Therefore, we investigated the changes in serum albumin levels in patients hospitalized for AHF. This observational study included 115 consecutive patients admitted with AHF. Serum albumin was measured on days 1, 2, 4, and 7 of their hospitalization, and the changes in its levels were assessed. Cox multivariate analysis was used to compare the long-term mortality and readmission rate between 2 groups defined according to whether their serum albumin changes showed a rising pattern (serum albumin level increased from day 2 to day 7) or not. The mean serum albumin levels were 3.51 mg/dl on day 1, 3.21 mg/dl on day 2, 3.23 mg/dl on day 4, and 3.35 mg/dl on day 7 (p <0.001 by multivariate analysis of variance). The rising pattern group including 66 patients (60.6%) was independently associated with a lower mortality and readmission rate (hazard ratios 0.450 and 0.522; p = 0.01 and 0.02, respectively). Furthermore, based on multiple linear regression analysis, the changes in hemoglobin and C-reactive protein levels during days 1 to 7 were independently correlated with the changes in serum albumin levels over the same period. In conclusion, a rising pattern of serum albumin change in a patient with AHF was correlated with a good long-term prognosis. Furthermore, the change in serum albumin levels was also associated with changes in cachectic factors.

Left ventricular end-diastolic pressure and ejection fraction correlate independently with high-sensitivity cardiac troponin-T concentrations in stable heart failure.

BACKGROUND: Cardiac troponin is widely accepted as a biomarker of myocyte injury in patients with myocardial ischemia. Patients with congestive heart failure are also associated with elevated cardiac troponin and it is a very sensitive prognostic marker. However, the mechanisms of troponin elevation in patients with heart failure are not fully understood. Decompensated state itself is suggested as a factor contributing to elevated cardiac troponin-T. However comparison between invasive hemodynamic parameters and cardiac troponin-T is insufficient. METHODS: Data were collected from 167 patients in stable, chronic HF, without acute coronary syndrome, recent revascularization, mitral stenoses, hemodialysis, or clinically significant right HF. We evaluated the correlations and 95% confidence intervals (CI) between invasive hemodynamic measurements and serum high-sensitivity (hs) concentrations of cTnT. RESULTS: The serum cTnT concentration was equal to or more than the detection threshold (0.003ng/ml) in all patients. The serum cTnT concentration was equal to or more than the cut-off value of 0.014ng/ml in 46% of patients. By multiple variable analysis, left ventricular (LV) end-diastolic pressure (EDP; adjusted coefficient=0.014; 95% CI 0.0003-0.029; P=0.046) was positively correlated, while hemoglobin (adjusted coefficient=-0.079; 95% CI -0.140 to -0.018; P=0.012), estimated glomerular filtration rate (adjusted coefficient=-0.008; 95% CI -0.013 to -0.003; P=0.004), and LV ejection fraction (EF; adjusted coefficient=-0.011; 95% CI -0.018 to -0.003; P=0.004) were negatively correlated with hs-cTnT concentrations. CONCLUSION: In patients with stable chronic HF, LVEDP and LVEF correlate with the serum concentrations of hs-cTnT, independently of other correlates of elevated plasma concentrations of hs-cTnT.

Ventricular Tachycardia Rotating a Scar of a Total Right Ventricular Exclusion.

We describe a 15-year-old postoperative girl who underwent surgical 3-dimensional mapping and ablation of hemodynamically unstable ventricular tachycardia (VT) with an on-pump beating heart surgical technique. She had previously received a tricuspid valve closure, entire right ventricular free wall resection, and finally Fontan operation with an extracardiac conduit to treat a severe Ebstein's anomaly. Activation mapping revealed a VT rotating around a large right ventricular free wall incisional scar with a narrow conduction channel between the scar and a tricuspid annulus (TA). A linear radiofrequency ablation connecting the scar and the TA terminated the VT.

Final 3-Year Outcome of a Randomized Trial Comparing Second-Generation Drug-Eluting Stents Using Either Biodegradable Polymer or Durable Polymer: NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial.

BACKGROUND: There is a paucity of data reporting the clinical outcomes of biodegradable polymer biolimus-eluting stent (BP-BES) compared with durable polymer everolimus-eluting stent (DP-EES) beyond 1 year after stent implantation when the polymer is fully degraded. METHODS AND RESULTS: The NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial (NEXT) is a prospective, multicenter, randomized, open-label, noninferiority trial comparing BP-BES with DP-EES in patients scheduled for percutaneous coronary intervention using drug-eluting stent (DES) without any exclusion criteria among 98 participating centers in Japan. The trial was designed to evaluate noninferiority of BP-BES relative to DP-EES in terms of any target-lesion revascularization at 1 year and death or myocardial infarction at 3 years. Between May and October 2011, 3235 patients were randomly assigned to receive either BP-BES (1617 patients) or DP-EES (1618 patients). Complete 3-year follow-up was achieved in 97.6% of patients. At 3 years, the primary safety end point of death or myocardial infarction occurred in 159 patients (9.9%) in the BP-BES group and in 166 patients (10.3%) in the DP-EES group, demonstrating noninferiority of BP-BES relative to DP-EES (P noninferiority<0.0001 and P superiority=0.7). Cumulative incidence of target-lesion revascularization was not significantly different between the 2 groups (7.4% versus 7.1%; P=0.8). By a landmark analysis at 1 year, the cumulative incidences of death or myocardial infarction and target-lesion revascularization were also not significantly different between the 2 groups (4.6% versus 5.2%; P=0.46 and 3.3% versus 2.7%; P=0.39, respectively). CONCLUSIONS: Safety and efficacy outcomes of BP-BES were non inferior to those of DP-EES 3 years after stent implantation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01303640.

Clinical efficacy of thrombus aspiration on 5-year clinical outcomes in patients with ST-segment elevation acute myocardial infarction undergoing percutaneous coronary intervention.

BACKGROUND: Adjunctive thrombus aspiration (TA) during primary percutaneous coronary intervention (PCI) was reported to promote better coronary and myocardial reperfusion. However, long-term mortality benefit of TA remains controversial. The objective of this study is to investigate the clinical impact of TA on long-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. METHODS AND RESULTS: The CREDO-Kyoto AMI Registry is a large-scale cohort study of acute myocardial infarction patients undergoing coronary revascularization in 2005-2007 at 26 hospitals in Japan. Among 5429 patients enrolled in the registry, the current study population consisted of 3536 patients who arrived at the hospital within 12 hours after the symptom onset and underwent primary PCI. Clinical outcomes were compared between the 2 patient groups with or without TA. During primary PCI procedures, 2239 out of 3536 (63%) patients underwent TA (TA group). The cumulative 5-year incidence of all-cause death was significantly lower in the TA group than in the non-TA group (18.5% versus 23.9%, log-rank P<0.001). After adjusting for confounders, however, the risk for all-cause death in the TA group was not significantly lower than that in the non-TA group (hazard ratio: 0.90, 95% CI: 0.76 to 1.06, P=0.21). The adjusted risks for cardiac death, myocardial infarction, stroke, and target-lesion revascularization were also not significantly different between the 2 groups. CONCLUSIONS: Adjunctive TA during primary PCI was not associated with better 5-year mortality in STEMI patients.

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.

Evolution in practice patterns and long-term outcomes of coronary revascularization from bare-metal stent era to drug-eluting stent era in Japan.

Treatment of coronary artery disease has significantly changed over the past decade including an introduction of drug-eluting stents and a more stringent adherence to evidence-based medications. However, the impact of these advanced treatment methods on the practice patterns and long-term outcomes in patients undergoing coronary revascularization in the real world has not been yet fully evaluated. The present study population consisted of the 2 groups of patients who underwent their first coronary revascularization in the Coronary REvascularization Demonstrating Outcome Study in Kyoto Registry Cohort-1 (bare-metal stent era: January 2000 to December 2002, n = 8,986) and Cohort-2 (drug-eluting stent era: January 2005 to December 2007, n = 10,339). Compared with Cohort-1, the proportion of patients treated with percutaneous coronary intervention significantly increased in Cohort-2 (73% vs 81%, p <0.001), particularly for 3-vessel disease (50% vs 61%, p <0.001) and left main disease (18% vs 36%, p <0.001). Evidence-based medications were more frequently used in Cohort-2. The cumulative 2-year incidence of and the adjusted risk for all-cause death were not significantly different between Cohort-1 and Cohort-2 (6.2% vs 6.4%, p = 0.69, and hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.81 to 1.03, p = 0.15). Adjusted risks for both myocardial infarction and repeated coronary revascularization were significantly reduced in Cohort-2 compared with Cohort-1 (HR 0.80, 95% CI 0.67 to 0.96, p = 0.02, and HR 0.73, 95% CI 0.69 to 0.77, p <0.001, respectively). In conclusion, despite changes in treatment methods over time, the long-term mortality of patients undergoing coronary revascularization in the real-world clinical practice has not been changed, although there was a significant reduction of myocardial infarction and repeated coronary revascularization.

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.

Anticoagulant and antiplatelet therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.

The prevalence, intensity, safety, and efficacy of oral anticoagulation (OAC) in addition to dual antiplatelet therapy (DAPT) in "real-world" patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not yet been fully evaluated. In the Coronary REvascularization Demonstrating Outcome Study in Kyoto registry cohort-2, a total of 1,057 patients with AF (8.3%) were identified among 12,716 patients undergoing first PCI. Cumulative 5-year incidence of stroke was higher in patients with AF than in no-AF patients (12.8% vs 5.8%, p <0.0001). Although most patients with AF had CHADS2 score ≥2 (75.2%), only 506 patients (47.9%) received OAC with warfarin at hospital discharge. Cumulative 5-year incidence of stroke in the OAC group was not different from that in the no-OAC group (13.8% vs 11.8%, p = 0.49). Time in therapeutic range (TTR) was only 52.6% with an international normalized ratio of 1.6 to 2.6, and only 154 of 409 patients (37.7%) with international normalized ratio data had TTR ≥65%. Cumulative 5-year incidence of stroke in patients with TTR ≥65% was markedly lower than that in patients with TTR <65% (6.9% vs 15.1%, p = 0.01). In a 4-month landmark analysis in the OAC group, there was a trend for higher cumulative incidences of stroke and major bleeding in the on-DAPT (n = 286) than in the off-DAPT (n = 173) groups (15.1% vs 6.7%, p = 0.052 and 14.7% vs 8.7%, p = 0.10, respectively). In conclusion, OAC was underused and its intensity was mostly suboptimal in real-world patients with AF undergoing PCI, which lead to inadequate stroke prevention. Long-term DAPT in patients receiving OAC did not reduce stroke incidence.