Yoshihisa Nakagawa

Three-year follow-up after implantation of metallic coronary-artery stents

BACKGROUND Coronary-artery stents are known to reduce rates of restenosis after coronary angioplasty, but it is uncertain how long this benefit is maintained. METHODS We evaluated clinical and angiographic follow-up information for up to three years after the implantation of Palmaz-Schatz metallic coronary-artery stents in 143 patients with 147 lesions of native coronary arteries. RESULTS The rate of survival free of myocardial infarction, bypass surgery, and repeated coronary angioplasty for stented lesions was 74.6 percent at three years. After 14 months, revascularization of the stented lesion was necessary in only three patients (2.1 percent). In contrast, coronary angioplasty for a new lesion was required in 11 patients (7.7 percent). Follow-up coronary angiography of 137 lesions at six months, 114 lesions at one year, and 72 lesions at three years revealed a decrease in minimal luminal diameter from 2.54 +/- 0.44 mm immediately after stent implantation to 1.87 +/- 0.56 mm at six months, but no further decrease in diameter at one year (in patients with paired angiograms, 1.95 +/- 0.49 mm at both six months and one year). Significant late improvement in luminal diameter was observed at three years (in patients with paired angiograms, 1.94 +/- 0.48 mm at six months and 2.09 +/- 0.48 mm at three years; P < 0.001). CONCLUSIONS Clinical and angiographic outcomes up to three years after coronary-artery stenting were favorable, with a low rate of revascularization of the stented lesions. Late improvement in luminal diameter appears to occur between six months and three years.

Antiplatelet Therapy and Stent Thrombosis After Sirolimus-Eluting Stent Implantation

Background— The influences of antiplatelet therapy discontinuation on the risk of stent thrombosis and long-term clinical outcomes after drug-eluting stent implantation have not yet been addressed adequately. Methods and Results— In an observational study in Japan, 2-year outcomes were assessed in 10 778 patients undergoing sirolimus-eluting stent implantation. Data on status of antiplatelet therapy during follow-up were collected prospectively. Incidences of definite stent thrombosis were 0.34% at 30 days, 0.54% at 1 year, and 0.77% at 2 years. Thienopyridine use was maintained in 97%, 62%, and 50% of patients at 30 days, 1 year, and 2 years, respectively. Patients who discontinued both thienopyridine and aspirin had a significantly higher rate of stent thrombosis than those who continued both in the intervals of 31 to 180 days, 181 to 365 days, and 366 to 548 days after stent implantation (1.76% versus 0.1%, P<0.001; 0.72% versus 0.07%, P=0.02; and 2.1% versus 0.14%, P=0.004, respectively). When discontinuation of aspirin was taken into account, patients who discontinued thienopyridine only did not have an excess of stent thrombosis in any of the time intervals studied. Adjusted rates of death or myocardial infarction at 24 months were 4.1% for patients taking thienopyridine and 4.1% for patients not taking thienopyridine (P=0.99) in the 6-month landmark analysis. Conclusions— Discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine therapy only, was associated with an increased risk of stent thrombosis. Landmark analysis did not suggest an apparent clinical benefit of thienopyridine use beyond 6 months after sirolimus-eluting stent implantation.

Long-Term Clinical and Angiographic Follow-Up After Coronary Stent Placement in Native Coronary Arteries

Background—Although coronary stents have been proved effective in reducing clinical cardiac events for up to 3 to 5 years, longer term clinical and angiographic outcomes have not yet been fully clarified. Methods and Results—To evaluate longer term (7 to 11 years) outcome, clinical and angiographic follow-up information was analyzed in 405 patients with successful stenting in native coronary arteries. Primary or secondary stabilization, which was defined as freedom from death, coronary artery bypass grafting, and target lesion-percutaneous coronary intervention (TL-PCI) during the 14 months after the initial procedure or after the last TL-PCI, was achieved in 373 patients (92%) overall. Only 7 patients (1.7%) underwent TL-PCI more than twice. After the initial 14-month period, freedom from TL-PCI reached a plateau at 84.9% to 80.7% over 1 to 8 years. However, quantitative angiographic analysis in 179 lesions revealed a triphasic luminal response characterized by an early restenosis phase until 6 months, an intermediate-term regression phase from 6 months to 3 years, and a late renarrowing phase beyond 4 years. Minimal luminal diameter in 131 patients with complete serial data were 2.62±0.4 mm immediately after stenting, 2.0±0.49 mm at 6 months, 2.19±0.49 mm at 3 years, and 1.85±0.56 mm beyond 4 years (P <0.0001). Conclusions—The efficacy and safety of coronary stenting seemed to be clinically sustained at 7 to 11 years of follow-up. However, late luminal renarrowing beyond 4 years was common, which demonstrates the need for further follow-up.

Biodegradable Polymer Biolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent : A Randomized, Controlled, Noninferiority Trial

OBJECTIVES NEXT (NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial) was designed for evaluating the noninferiority of a biolimus-eluting stent (BES) relative to an everolimus-eluting stent (EES) in terms of target lesion revascularization (TLR) at 1 year. BACKGROUND Efficacy and safety data comparing biodegradable polymer BES with durable polymer cobalt-chromium EES are currently limited. METHODS The NEXT trial is a prospective, multicenter, randomized, open-label, noninferiority trial comparing BES with EES. Between May and October 2011, 3,235 patients were randomly assigned to receive either BES (n = 1,617) or EES (n = 1,618). RESULTS At 1 year, the primary efficacy endpoint of TLR occurred in 67 patients (4.2%) in the BES group, and in 66 patients (4.2%) in the EES group, demonstrating noninferiority of BES relative to EES (p for noninferiority <0.0001, and p for superiority = 0.93). Cumulative incidence of definite stent thrombosis was low and similar between the 2 groups (0.25% vs. 0.06%, p = 0.18). An angiographic substudy enrolling 528 patients (BES: n = 263, and EES: n = 265) demonstrated noninferiority of BES relative to EES regarding the primary angiographic endpoint of in-segment late loss (0.03 ± 0.39 mm vs. 0.06 ± 0.45 mm, p for noninferiority <0.0001, and p for superiority = 0.52) at 266 ± 43 days after stent implantation. CONCLUSIONS One-year clinical and angiographic outcome after BES implantation was noninferior to and not different from that after EES implantation in a mostly stable coronary artery disease population. One-year clinical outcome after both BES and EES use was excellent, with a low rate of TLR and extremely low rate of stent thrombosis.

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: . Unique identifier: [NCT01035450][1]. # Clinical Perspective {#article-title-27} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01035450&atom=%2Fcirculationaha%2F126%2F10%2F1225.atomBackground— 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 (Pnoninferiority<0.0001, and Psuperiority=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, Pnoninferiority<0.0001, and Psuperiority=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.

Statistical analysis of clinical risk factors for coronary artery spasm: Identification of the most important determinant

Coronary artery spasm plays an important role in acute ischemic events, and it has a close relationship with coronary atherosclerosis. Thus we attempted to determine the most significant risk factor for coronary artery spasm. Among 3000 consecutive patients who underwent coronary cineangiography with ergonovine maleate testing, 330 with typical angina pectoris (group 1) and 294 with old myocardial infarction (group 2) were studied. We divided each group into three or four subgroups according to the presence of fixed organic stenosis (FOS+) or a positive reaction to ergonovine maleate (coronary artery spasm [CAS]+). We examined the relationship between coronary artery spasm and eight coronary risk factors: age, sex, hypertension, diabetes mellitus, smoking, and serum cholesterol, uric acid, and high-density lipoprotein cholesterol levels. The proportion of smokers in the subgroups with CAS(+) was significantly higher than in the subgroups with CAS(-)(p less than 0.01). There was no correlation between smoking and fixed organic stenosis. According to the results of multiple regression analysis, there was a positive correlation between smoking and CAS(+) and between serum high-density lipoprotein cholesterol levels and CAS(+)(p less than 0.01). Thus we concluded that smoking is the most significant risk factor in discriminating between patients with and without coronary artery spasm.

Thrombectomy with AngioJet catheter in native coronary arteries for patients with acute or recent myocardial infarction

The AngioJet thrombectomy catheter removes thrombi by rheolytic fragmentation and suction. The purpose of this study was to identify the efficacy and safety of this new device. Myocardial infarction (MI) is associated with intracoronary thrombus. Intracoronary thrombus has been identified as a risk factor of unfavorable outcome after percutaneous transluminal coronary angioplasty. To what extent the AngioJet is applicable or effective for acute or recent MI in native coronary artery is not clear. Thrombectomy with the AngioJet was attempted in 31 patients with 31 native coronary arteries selected from 304 patients with acute or recent MI. Follow-up angiography was performed at 3 to 6 months. Procedure success was achieved in 29 patients (94%). Adjunctive balloon angioplasty was performed after AngioJet thrombectomy in 30 patients (97%), and in only 1 patient (3%) AngioJet thrombectomy was the sole procedure. Subsequent stenting after balloon angioplasty was attempted successfully in 12 patients (40%) without thrombotic complications. Thrombolysis In Myocardial Infarction trial flow grading increased from 0.70 +/- 0.97 before to 2.61 +/- 0.88 after AngioJet thrombectomy (p <0.0001), to 2.84 +/- 0.64 after adjunctive procedures (p = 0.070). At follow-up angiography restenosis rate was 21% but Thrombolysis In Myocardial Infarction flow 3 was present in all patients. The restenosis rate of stented patients was 8%. There were no major events during in-hospital and follow-up. The AngioJet can be used safely and successfully to remove thrombus from the native coronary artery of patients with MI. Thrombus removal makes subsequent stenting safe and uncomplicated. The restenosis rate was considered to be acceptable.

Pathological analyses of long-term intracoronary Palmaz-Schatz stenting; Is its efficacy permanent?

BACKGROUND Angiographic regression of luminal narrowing occurs 6 months to 3 years poststenting. However, after 4 years lesions progressed gradually and late restenosis was observed in 28% of 179 Palmaz-Schatz-stented lesions during the past 10 years. Elucidating its pathogenesis is pivotal to developing preventive strategies. METHODS AND RESULTS Histopathological and immunohistochemical studies were performed in 19 stented coronary arteries obtained from 19 patients autopsied after noncardiac death 2-7 years poststenting. The quality/severity of chronic inflammatory cells (T lymphocytes, macrophages and multinucleated giant cells) infiltration around the stent struts that is observed even in the absence of restenosis depended on the time elapsed from stenting: a) 2 years postprocedure, in spite of angiographic regression during the first year and pathologically expressed as maturation of the neointimal scar, there was chronic inflammatory response evidence: neovascularization and lymphocyte infiltration, b) > or = 3 years: the neointimal smooth muscle cells were sparse with abundant proliferation of collagen fibers. Presence of slight helper/inducer T lymphocytes and mild macrophage infiltration around the stent struts was evident immunohistochemically, c) > or = 4 years: prominent infiltration by lipid-laden macrophages with strong collagen-degrading matrix metalloproteinase immunoreactivity was observed around the struts. In two of these arteries, the surface contacting the stent was focally disrupted and covered by nonocclusive mural thrombi. CONCLUSIONS Stainless steel stents evoke a remarkable foreign-body inflammatory reaction to the metal. These persistent peri-strut chronic inflammatory cells may accelerate new indolent atherosclerotic changes and consequent plaque vulnerability.

Association of onset to balloon and door to balloon time with long term clinical outcome in patients with ST elevation acute myocardial infarction having primary percutaneous coronary intervention: observational study.

Objective To evaluate the relation of symptom onset to balloon time and door to balloon time with long term clinical outcome in patients with ST segment elevation myocardial infarction (STEMI) having primary percutaneous coronary intervention. Design Observation of large cohort of patients with acute myocardial infarction. Setting 26 tertiary hospitals in Japan. Participants 3391 patients with STEMI who had primary percutaneous coronary intervention within 24 hours of symptom onset. Main outcome measures Composite of death and congestive heart failure, compared by onset to balloon time and door to balloon time. Results Compared with an onset to balloon time greater than 3 hours, a time of less than 3 hours was associated with a lower incidence of a composite of death and congestive heart failure (13.5% (123/964) v 19.2% (429/2427), P<0.001; relative risk reduction 29.7%). After adjustment for confounders, a short onset to balloon time was independently associated with a lower risk of the composite endpoint (adjusted hazard ratio 0.70, 95% confidence interval 0.56 to 0.88; P=0.002). However, no significant difference was found in the incidence of a composite of death and congestive heart failure between the two groups of patients with short (≤90 minutes) and long (>90 minutes) door to balloon time (16.7% (270/1671) v 18.4% (282/1720), P=0.54; relative risk reduction 9.2%). After adjustment for confounders, no significant difference was seen in the risk of the composite endpoint between the two groups of patients with short and long door to balloon time (adjusted hazard ratio: 0.98, 0.78 to 1.24: P=0.87). A door to balloon time of less than 90 minutes was associated with a lower incidence of a composite of death and congestive heart failure in patients who presented within 2 hours of symptom onset (11.9% (74/883) v 18.1% (147/655), P=0.01; relative risk reduction 34.3%) but not in patients who presented later (19.7% (196/788) v 18.7% (135/1065), P=0.44; −5.3%). Short door to balloon time was independently associated with a lower risk of a composite of death and congestive heart failure in patients with early presentation (adjusted hazard ratio 0.58, 0.38 to 0.87; P=0.009) but not in patients with delayed presentation (1.57, 1.12 to 2.18; P=0.008). A significant interaction was seen between door to balloon time and time to presentation (interaction P=0.01). Conclusions Short onset to balloon time was associated with better 3 year clinical outcome in patients with STEMI having primary percutaneous coronary intervention, whereas the benefit of short door to balloon time was limited to patients who presented early. Efforts to minimise onset to balloon time, including reduction of patient related delay, should be recommended to improve clinical outcome in STEMI patients.

Incidence and Risk Factors of Late Target Lesion Revascularization After Sirolimus-Eluting Stent Implantation (3-Year Follow-Up of the j-Cypher Registry)

It yet has not been clarified whether there is a late catch-up phenomenon in target lesion revascularization (TLR) after sirolimus-eluting stent (SES) compared to bare metal stent (BMS) implantation. In 12,824 patients enrolled in the j-Cypher Registry, incidences of early (within first year) and late (1 year to 3 years) TLR were compared between 17,050 lesions treated with SESs and 1,259 lesions treated with BMSs. Incidences of TLR in SES-treated lesions were 5.7% at 1 year, 8.1% at 2 years, and 10.0% at 3 years, whereas those in BMS-treated lesions were 14.2%, 15.5%, and 15.5%, respectively (p <0.0001, log-rank test). Incidences of late TLR were significantly higher with SESs compared to BMSs (2.6% vs 1.4% at 2 years and 4.5% vs 1.4% at 3 years, p = 0.0007, log-rank test). A multivariable logistic regression model identified 7 independent risk factors for late TLR at 3 years after SES implantation: hemodialysis, low estimated glomerular filtration rate, ostial right coronary artery, lesion length >or=30 mm, 2 stents for bifurcation, American Heart Association/American College of Cardiology type B2/C, and vessel size <2.5 mm. Of these, 5 factors were common to those for early TLR. In conclusion, a late catch-up phenomenon was observed as indicated by the increasing incidence of late TLR after SES, but not after BMS, implantation. Risk factors for late TLR were generally common to those for early TLR.