Tomohisa Tada

Incidence and predictors of restenosis after coronary stenting in 10 004 patients with surveillance angiography

Objective Systematic investigation of restenosis after percutaneous coronary intervention (PCI) with bare metal stents (BMS) or first or second generation drug eluting stents (DES) in large scale, broadly inclusive patient populations undergoing follow-up angiography represents a gap in our scientific knowledge. We investigated the incidence of angiographically proven restenosis and its predictors in patients undergoing PCI with stents. Methods All patients undergoing successful implantation of coronary stents for de novo lesions from 1998 to 2009 and follow-up angiography at 6–8 months at two centres in Munich, Germany were eligible for inclusion. Patients with cardiogenic shock, dialysis dependent renal insufficiency or previous cardiac transplantation were excluded. Data were prospectively collected. The incidence of restenosis, defined as diameter stenosis ≥50% in the in-segment area at follow-up angiography, and its predictors were evaluated. Results A total of 12 094 patients met inclusion criteria. Angiographic follow-up was available for 10 004 patients (77.5%) with 15 004 treated lesions. Binary restenosis was detected in 2643 (26.4%) patients. Use of first generation DES versus BMS (OR 0.35, 95% CI 0.31 to 0.39) and second generation DES versus first generation DES (OR 0.67, 95% CI 0.58 to 0.77) were independent predictors of lower rates of restenosis. At multivariate analysis, smaller vessel size (OR 1.59, 95% CI 1.52 to 1.68, for each 0.5 mm decrease), total stented length (OR 1.27, 95% CI 1.21 to 1.33, for each 10 mm increase), complex lesion morphology (OR 1.35, 95% 1.21 to 1.51), presence of diabetes mellitus (OR 1.32, 95% 1.19 to 1.46), and history of bypass surgery (OR 1.38, 95% CI 1.20 to 1.58) were independently associated with restenosis and were similar across the spectrum of stent devices. Conclusions In this large cohort of patients with angiographic surveillance we demonstrated the impact of device development on antirestenotic efficacy, with sequentially improved efficacy from BMS to first generation DES to second generation DES. Predictors of restenosis were small vessel size, increased stented length, complex lesion morphology, diabetes mellitus, and prior bypass surgery.

Clinical impact of extended dual antiplatelet therapy after percutaneous coronary interventions in the drug-eluting stent era: a meta-analysis of randomized trials

AIMS The aim of this study was to evaluate benefits and risks of extending dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in the drug-eluting stent era. METHODS AND RESULTS We searched electronic databases (Medline, EMBASE, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, chapters in books, and proceedings of advisory panels for the US Food and Drug Administration, for randomized controlled trials investigating the clinical impact of extending DAPT duration in patients undergoing PCI. The primary endpoint was all-cause death. The secondary endpoints were myocardial infarction (MI), stent thrombosis (ST), cerebrovascular accidents (CVAs), and thrombolysis in myocardial infarction (TIMI) major bleeding. We included four trials that randomized 8231 patients (50.2%, extended DAPT duration vs. 49.8%, control duration). A total of 8158 patients (99.1%) were available for final analyses. The median DAPT duration was 16.8 vs. 6.2 months for the extended DAPT and control groups, respectively. At follow-up (median 16.8 months) extending DAPT duration did not reduce all-cause death [odds ratio (95% confidence interval) = 1.15 (0.85-1.54), P = 0.36], MI [0.95 (0.66-1.36), P = 0.77], ST [0.88 (0.43-1.81), P = 0.73], or CVAs [1.51 (0.92-2.47), P = 0.10]. Conversely, extended DAPT duration clearly increased the risk of TIMI major bleeding [2.64 (1.31-5.30), P = 0.006]. CONCLUSIONS The extension of DAPT duration after percutaneous coronary interventions may increase the risk of bleeding without reducing ischaemic events. These results need corroboration from large ongoing trials.

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.

Tissue Characterization After Drug-Eluting Stent Implantation Using Optical Coherence Tomography

Objective—To validate optical coherence tomography (OCT) imaging for assessment of vascular healing in a preclinical animal model and human autopsy cases and to translate the findings to the assessment of vascular healing after drug-eluting stent implantation in clinical practice. Approach and Results—Drug-eluting and bare metal stents were imaged 28 and 42 days after implantation in atherosclerotic rabbits using OCT and simultaneously evaluated by histology. After coregistration with histology, gray-scale signal intensity (GSI) was measured for identified mature or immature neointimal tissue. Autopsy specimens were imaged with OCT and GSI values correlated with histology. Finally, prospective OCT imaging and GSI measurements were acquired in 10 patients undergoing follow-up 6 months after stenting with drug-eluting stents. Histopathologic and OCT morphometric analysis of implanted stents showed excellent correlation. Neointimal growth and vessel healing at 28 days in the animal model best correlated with human stented arteries at 6 months. In animal and human autopsy specimens, mature neointimal tissue consistently showed higher GSI values. Receiver operating characteristic curve analysis displayed high sensitivity and specificity for detection of mature neointima in animal (96% and 79%, respectively) and human autopsy (89% and 71%, respectively) data. In patients undergoing OCT follow-up 6 months after drug-eluting stent implantation, prospective GSI analysis revealed that a minimum of 27.7% of areas above stent struts represented mature neointima. Conclusions—Novel GSI analysis of OCT imaging data allows distinction between mature and immature neointimal tissue in animal models, autopsy specimens, and patients undergoing invasive surveillance in simple atherosclerotic lesions.

Duration of Dual Antiplatelet Therapy and Long-Term Clinical Outcome After Coronary Drug-Eluting Stent Implantation Landmark Analyses From the CREDO-Kyoto PCI/CABG Registry Cohort-2

Background— Optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation has not been yet fully elucidated. Methods and Results— We assessed the influence of prolonged thienopyridine therapy on clinical outcomes with landmark analysis at 4 and 13 months after DES implantation. Among 6802 patients with at least 1 DES implantation in the CREDO-Kyoto Registry Cohort-2, 6309 patients (on thienopyridine, 5438 patients; off thienopyridine, 871 patients) and 5901 patients (on thienopyridine, 4098 patients; off thienopyridine, 1803 patients) were eligible for the 4- and 13-month landmark analyses, respectively. The majority of patients had stable coronary artery disease (73%) and received sirolimus-eluting stents (93%), and approximately 90% of thienopyridine was ticlopidine. Patients taking thienopyridine had more complex comorbidities and more complex lesion and procedural characteristics as compared with patients not taking thienopyridine. After adjusting for confounders, thienopyridine use was not associated with decreased risk for death/myocardial infarction/stroke (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.89–1.43, P=0.32 in the 4-month landmark analysis; HR, 1.14; 95% CI, 0.90–1.45, P=0.29 in the 13-month landmark analysis, respectively), whereas the risk for GUSTO moderate/severe bleeding tended to be higher in patients taking thienopyridine (HR, 1.51; 95% CI, 1.00–2.23, P=0.049 in the 4-month landmark analysis; HR, 1.44; 95% CI, 0.99–2.09, P=0.057 in the 13-month landmark analysis, respectively). Conclusions— Prolonged thienopyridine therapy beyond 4 and 13 months appeared not to be associated with reduction in ischemic events but to be associated with a trend toward increased bleeding. Optimal duration of DAPT after DES implantation might be shorter than the currently recommended 1-year interval.

Comparison of Three-Year Clinical Outcomes After Sirolimus-Eluting Stent Implantation Among Insulin-Treated Diabetic, Non–Insulin-Treated Diabetic, and Non-Diabetic Patients from j-Cypher Registry

The purpose of the present study was to evaluate the 3-year clinical outcomes after percutaneous coronary intervention with sirolimus-eluting stents in patients with insulin-treated diabetes mellitus (DM-insulin) and those with non-insulin-treated DM (DM-non-insulin) compared to patients without DM. Of 10,778 consecutive patients treated exclusively with sirolimus-eluting stents in the j-Cypher registry, we identified 996 patients with DM-insulin, 3,404 with DM-non-insulin, and 6,378 without DM. Compared to the non-DM group, the adjusted risk of a serious cardiovascular event (composite of all-cause death, myocardial infarction, and stroke) was significantly greater in the DM-insulin group (hazard ratio 1.12, 95% confidence interval [CI] 1.03 to 1.23; p = 0.01), but not in the DM-non-insulin group (hazard ratio 1.02, 95% CI 0.96 to 1.09; p = 0.47). The adjusted risk of target lesion revascularization was significantly greater in both the DM-insulin group (odds ratio 1.52, 95% CI 1.19 to 1.92; p = 0.0006) and the DM-non-insulin group (odds ratio 1.24, 95% CI 1.05 to 1.45; p = 0.009). In conclusion, a diabetes-associated excess risk of target lesion revascularization was found, regardless of insulin use in this large, real-world study of Japanese patients with sirolimus-eluting stent implantation. However, regarding serious cardiovascular events, an excess risk was seen only in the DM-insulin group. The risk of serious cardiovascular events was similar between the DM-non-insulin and non-DM groups.

Comparative efficacy of 2 zotarolimus-eluting stent generations: Resolute versus endeavor stents in patients with coronary artery disease

BACKGROUND The Resolute zotarolimus-eluting stent (R-ZES) utilizes the same metallic platform and anti-restenotic drug as the Endeavor zotarolimus-eluting stent (E-ZES) but is coated with a more biocompatible polymer with enhanced drug-release kinetics. The aim of this study was to compare the long-term clinical outcomes of 2 zotarolimus-eluting stent generations. METHODS In two randomized trials with broad inclusion criteria (ISAR-TEST 2 and ISAR-TEST 5), 1,000 patients were treated with R-ZES and 339 patients treated with E-ZES. In both trials follow-up angiography was scheduled at 6 to 8 months. The efficacy endpoint of interest was target lesion revascularization and the safety endpoints were the combined incidence of cardiac death or myocardial infarction related to target vessel as well as the incidence of definite stent thrombosis at 2-year follow-up. RESULTS The incidence of target lesion revascularization at 2 years was 12.0% in the R-ZES group and 16.0% in the E-ZES (HR 0.72 [95% CI: 0.52-1.00], P = .052). The incidence of cardiac death or myocardial infarction was 5.5% vs. 4.8% (HR 1.15, [95% CI: 0.66-2.02], P = .62) and of definite stent thrombosis was 0.4% vs. 0.6% (HR 0.68, [95% CI: 0.12-3.72], P = .66), respectively. All measures of angiographic restenosis were in favor of the R-ZES; in-stent late lumen loss was 0.29 ± 0.56 with the R-ZES versus 0.58 ± 0.55 with the E-ZES (P < .0001). CONCLUSIONS Comparison of the 2 Food and Drug Administration-approved zotarolimus-eluting stents suggested that the R-ZES as compared to the E-ZES displayed overall superior antirestenotic efficacy. Both devices were associated with a similar low risk of adverse safety events through 2 years.

Uric acid and prognosis in angiography-proven coronary artery disease.

The optimal uric acid (UA) level associated with the lowest mortality and the strength of association between UA and mortality in various subgroups of patients with coronary artery disease (CAD) are unknown.

Bleeding after percutaneous coronary intervention in women and men matched for age, body mass index, and type of antithrombotic therapy.

BACKGROUND Factors underlying the increased risk of bleeding after percutaneous coronary intervention (PCI) in women compared with men remain incompletely understood. METHODS The study included 3,351 women and 3,351 men matched for age, body mass index, and type of antithrombotic therapy. Bleeding within the 30 days after PCI was defined using the Bleeding Academic Research Consortium criteria. The main outcome was 1-year mortality. RESULTS Bleeding occurred in 518 women and 354 men (15.5% vs 10.6%, odds ratio [OR] 1.55, 95% CI 1.34-1.79, P < .001). Severe (Bleeding Academic Research Consortium class ≥2) bleeds (9.4% vs 6.5%, P < .001) and access site bleeds (10.1% vs 5.4%, P < .001) were more common in women. After adjustment, female sex remained an independent correlate of any bleeding (adjusted OR 1.61 [1.35-1.92], P < .001) and access site (adjusted OR 2.00 [1.59-2.50], P < .001) but not of nonaccess site (adjusted OR 1.18 [0.91-1.54], P = .205) bleeding. There were 248 deaths: 32 deaths among men with bleeding versus 107 deaths among men with no bleeding (9.1% vs 3.6%, OR 2.68 [1.78-4.05], P < .001) and 40 deaths among women with bleeding vs 69 deaths among women with no bleeding (7.8% vs 2.5%, OR 3.35 [2.24-5.01], P < .001). No difference in mortality was observed among women and men who bled (P = .487). Bleeding was independently associated 1-year mortality (adjusted hazard ratio 2.18 [1.68-2.84], P < .001) with no bleeding-by-sex interaction (P = .439). CONCLUSIONS Despite matching for age, body mass index, and type of antithrombotic therapy, bleeding risk after PCI remained significantly higher in women than in men. Bleeding was associated with increased risk of 1-year mortality with no bleeding-by-sex interaction.

Optical Coherence Tomography Findings in Patients With Coronary Stent Thrombosis A Report of the PRESTIGE Consortium (Prevention of Late Stent Thrombosis by an Interdisciplinary Global European Effort)

Background: Stent thrombosis (ST) is a serious complication following coronary stenting. Intravascular optical coherence tomography (OCT) may provide insights into mechanistic processes leading to ST. We performed a prospective, multicenter study to evaluate OCT findings in patients with ST. Methods: Consecutive patients presenting with ST were prospectively enrolled in a registry by using a centralized telephone registration system. After angiographic confirmation of ST, OCT imaging of the culprit vessel was performed with frequency domain OCT. Clinical data were collected according to a standardized protocol. OCT acquisitions were analyzed at a core laboratory. Dominant and contributing findings were adjudicated by an imaging adjudication committee. Results: Two hundred thirty-one patients presenting with ST underwent OCT imaging; 14 (6.1%) had image quality precluding further analysis. Of the remaining patients, 62 (28.6%) and 155 (71.4%) presented with early and late/very late ST, respectively. The underlying stent type was a new-generation drug-eluting stent in 50.3%. Mean reference vessel diameter was 2.9±0.6 mm and mean reference vessel area was 6.8±2.6 mm2. Stent underexpansion (stent expansion index <0.8) was observed in 44.4% of patients. The predicted average probability (95% confidence interval) that any frame had uncovered (or thrombus-covered) struts was 99.3% (96.1–99.9), 96.6% (92.4–98.5), 34.3% (15.0–60.7), and 9.6% (6.2–14.5) and malapposed struts was 21.8% (8.4–45.6), 8.5% (4.6–15.3), 6.7% (2.5–16.3), and 2.0% (1.2–3.3) for acute, subacute, late, and very late ST, respectively. The most common dominant finding adjudicated for acute ST was uncovered struts (66.7% of cases); for subacute ST, the most common dominant finding was uncovered struts (61.7%) and underexpansion (25.5%); for late ST, the most common dominant finding was uncovered struts (33.3%) and severe restenosis (19.1%); and for very late ST, the most common dominant finding was neoatherosclerosis (31.3%) and uncovered struts (20.2%). In patients presenting very late ST, uncovered stent struts were a common dominant finding in drug-eluting stents, and neoatherosclerosis was a common dominant finding in bare metal stents. Conclusions: In patients with ST, uncovered and malapposed struts were frequently observed with the incidence of both decreasing with longer time intervals between stent implantation and presentation. The most frequent dominant observation varied according to time intervals from index stenting: uncovered struts and underexpansion in acute/subacute ST and neoatherosclerosis and uncovered struts in late/very late ST.