De Novo Native Coronary Lesions Research Articles

Favorable Vasomotor Function after Drug-Coated Balloon-Only Angioplasty of De Novo Native Coronary Artery Lesions.

Balloon-injured coronary segments are known to harbor abnormal vasomotion. We evaluated whether de novo coronary lesions treated using drug-coated balloon (DCB) are prone to vasospasm and how they respond to ergonovine and nitrate. Among 132 DCB angioplasty recipients followed, 89 patients underwent ergonovine provocation test at 6–9 months follow-up. Within-subject ergonovine- and nitrate-induced diameter changes were compared among three different sites: DCB-treated vs. angiographically normal vs. segment showing prominent vasoreactivity (spastic). No patient experienced clinically refractory vasospastic angina or symptom-driven revascularization during follow-up. Ergonovine induced vasospasm in seven patients; all were multifocal spasm either involving (n = 2) or rather sparing DCB-treated segments (n = 5). None showed focal spasm that exclusively involved DCB-treated lesions. Among 27 patients with vasospastic features, DCB-treated segments showed less vasoconstriction than spastic counterparts (p < 0.001). A total of 110 DCB-treated lesions were analyzed to assess vasomotor function. Vasomotor function, defined as a combined constrictor and dilator response, was comparable between DCB-treated and angiographically normal segments (p = 0.173), while significant differences were observed against spastic counterparts (p < 0.001). In our study, DCB-treated lesions were not particularly vulnerable to vasospasm and were found to have vasomotor function similar to angiographically normal segments, supporting safety of DCB-only strategy in treating de novo native coronary lesions.

Atypical “vacuum” inside of neoatherosclerosis long term after DES implantation: Insights from optical coherence tomography

Percutaneous coronary intervention (PCI) with stenting is the most widely performed procedure for the treatment of symptomatic coronary artery disease [ [1] Serruys P.W. et al. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N. Engl. J. Med. 1994; 331: 489-495 Crossref PubMed Scopus (4365) Google Scholar ], and the technological developments of drug-eluting stents (DES) have reduced the rates of in-stent restenosis and target lesion revascularization of bare-metal stent [ 2 Morice M.C. et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N. Engl. J. Med. 2002; 346: 1773-1780 Crossref PubMed Scopus (3859) Google Scholar , 3 Fajadet J. et al. Maintenance of long-term clinical benefit with sirolimus-eluting coronary stents: three-year results of the RAVEL trial. Circulation. 2005; 111: 1040-1044 Crossref PubMed Scopus (216) Google Scholar , 4 Moses J. et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N. Engl. J. Med. 2003; 349: 1315-1323 Crossref PubMed Scopus (4060) Google Scholar , 5 Weiz G. et al. Five-year follow-up after sirolimus-eluting stent implantation: results of the SIRIUS (Sirolimus-Eluting Stent in De-Novo Native Coronary Lesions) trial. J. Am. Coll. Cardiol. 2009; 53: 1488-1497 Abstract Full Text Full Text PDF PubMed Scopus (183) Google Scholar ]. Clinical and histological studies of DES have confirmed evidence that restenosis is the result of arterial damage with subsequent neointimal tissue proliferation, which was named as “late catch-up” phenomenon [ 6 Grube et al. TAXUS VI final 5-year results: a multicentre, randomised trial comparing polymer-based moderate-release paclitaxel-eluting stent with a bare metal stent for treatment of long, complex coronary artery lesions. EuroIntervention. 2009; 4: 572-577 Crossref PubMed Scopus (58) Google Scholar , 7 Nakazawa et al. Coronary responses and differential mechanisms of late stent thrombosis attributed to first-generation sirolimus- and paclitaxel-eluting stents. J. Am. Coll. Cardiol. 2011; 57: 390-398 Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar ]. The mechanisms behind this DES failure remain complex and multi-factorial. The atherosclerotic changes (neoatherosclerosis) of neointimal layer inside of a restenosis are now thought to be potential mechanisms of DES failure [ [8] Park S.J. et al. In-stent neoatherosclerosis: a final common pathway of late stent failure. J. Am. Coll. Cardiol. 2012; 59: 2051-2057 Abstract Full Text Full Text PDF PubMed Scopus (301) Google Scholar ]. The exact pathogenesis of neoatherosclerosis remains partially unknown, however Yonetsu et al. have shown that the risk factors such as stent >48 months old, DES, cigarette smoking and chronic kidney disease are strongly associated with the formation of neoatherosclerosis, whereas the use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers appears to be protective [ [9] Yonetsu et al. Predictors for neoatherosclerosis: a retrospective observational study from the optical coherence tomography registry. Circ. Cardiovasc. Imaging. 2012; 5: 660-666 Crossref PubMed Scopus (126) Google Scholar ]. We present a case of atypical “vacuum” inside neoatherosclerotic pattern of restenosis after DES implantation where the OCT was used to describe this new report of neoatherosclerosis and to demonstrate probable causes of it.

TCTAP A-002 Long Term Safety and Performance of Absorb Bioresorbable Vascular Scaffold in Treating De Novo Native Coronary Lesions: Report on 3-year Clinical Outcomes from the First 450 Patients in ABSORB EXTEND

TCTAP A-002 Long Term Safety and Performance of Absorb Bioresorbable Vascular Scaffold in Treating De Novo Native Coronary Lesions: Report on 3-year Clinical Outcomes from the First 450 Patients in ABSORB EXTEND

Retrospective Comparison of the Clinical and Angiographic Outcomes of the Sirolimus-eluting Stent and the Bare-metal Stent in 2031 Nonrandomized Consecutive De Novo Native Coronary Lesions

To evaluate the mid-term outcomes of sirolimus-eluting stents (SES; Cypher Bx Velocity) for de novo coronary stenosis in a Japanese clinical setting, and to compare these with the outcomes using bare-metal stents (BMS). This study was a nonrandomized, lesion-based, and single-center study, retrospectively investigated in October 2010. We enrolled 2031 consecutive cases with de novo coronary lesions treated with BMS (n=587) or SES (n=1,444) from January 2003 to May 2007. SES use ratio during the available interval was 95.5%. The primary endpoint was the incidence of target vessel failure (TVF: comprising cardiac death, nonfatal recurrent MI, definite stent thrombosis (ST), and severe restenosis [% diameter stenosis (%DS) at secondary angiography ≥70%]. The secondary endpoint was the incidence of binary in-stent restenosis (%DS >50%). The TVF ratio after SES placement (6.6%) was significantly lower than that after BMS placement (11.8%, p<0.001), despite many disadvantageous variables in the SES group. SES related to the risk of TVF (mean follow-up for SES, 1,411 ± 539 days; BMS, 1,818 ± 825 days) (hazard ratio of 0.428 at 95% CI, 0.292-0.627, p<0.001). The ratio of binary in-stent restenosis after SES placement (13.4%) was significantly lower than that after BMS placement (25.1%; p<0.001). SES was significantly related to binary in-stent restenosis (odds ratio of 0.267 at 95% CI, 0.195-0.366, p<0.001). SES has a more favorable mid-term clinical and angiographic outcome than BMS for de novo coronary stenosis in clinical settings in Japan.

Improved Late Clinical Safety With Zotarolimus-Eluting Stents Compared With Paclitaxel-Eluting Stents in Patients With De Novo Coronary Lesions: 3-Year Follow-Up From the ENDEAVOR IV (Randomized Comparison of Zotarolimus- and Paclitaxel-Eluting Stents in Patients With Coronary Artery Disease) Trial

The increased frequency of very late (>1 year) stent thrombosis (VLST) has raised concerns with regard to the safety of sirolimus-eluting stents and paclitaxel-eluting stents (PES). Experimental and preliminary clinical findings with the zotarolimus-eluting stent (ZES) have suggested a favorable safety profile. The ENDEAVOR IV (Randomized Comparison of Zotarolimus- and Paclitaxel-Eluting Stents in Patients With Coronary Artery Disease) trial is a single-blind randomized ZES versus PES clinical trial in 1,548 patients with de novo native coronary lesions; the primary end point-9-month target vessel failure-was previously reported, annual clinical follow-up is planned for 5 years, and this report describes the 3-year outcomes. The ZES compared with PES reduced target vessel failure (12.3% vs. 15.9%, hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.58 to 1.00, p = 0.049), myocardial infarctions (MI) (2.1% vs. 4.9%, HR: 0.44, 95% CI: 0.25 to 0.80, p = 0.005), and cardiac death plus MI (3.6% vs. 7.1%, HR: 0.52, 95% CI 0.32 to 0.82, p = 0.004). Although the overall 3-year rate of Academic Research Consortium definite/probable stent thrombosis did not differ significantly (1.1% vs. 1.7%, HR: 0.67, 95% CI 0.28 to 1.64, p = 0.380), VLST (between 1 and 3 years) was significantly reduced in ZES patients (1 event vs. 11 events; 0.1% vs. 1.6%, HR: 0.09, 95% CI: 0.01 to 0.71, p = 0.004). Ischemia-driven target lesion revascularization at 3 years was similar with ZES versus PES (6.5% vs. 6.1%, HR: 1.10, 95% CI: 0.73 to 1.65, p = 0.662). Three-year follow-up results from the ENDEAVOR IV trial indicate similar antirestenosis efficacy but improved clinical safety associated with ZES compared with PES, due to significantly fewer peri-procedural and remote MIs associated with fewer VLST events. (A Randomized, Controlled Trial of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the Taxus Paclitaxel-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions; NCT00217269).

Effect of Coronary Target Lesion Revascularization on Late Cardiac Events After Insertion of Sirolimus-Eluting or Bare Metal Stents

Restenosis is associated with acute myocardial infarction (MI) either at presentation or related to complications of target lesion revascularization (TLR). The cumulative late effect of TLR after drug-eluting or bare metal stent placement on cardiac death or MI is uncertain. Of the 1,057 patients with one native coronary lesion randomized to a sirolimus-eluting stent or bare metal stent in the Sirolimus-Eluting Stent in De Novo Native Coronary Lesions (SIRIUS) trial, the 983 who survived free of MI for the first 30 days were evaluated for the primary outcome of cardiac death or MI for 5 years. Patients with events occurring at or after TLR were assigned to TLR group. Cox proportional hazards regression analysis with TLR as a time-dependent variable and adjustment for baseline clinical and demographic covariates was used to assess the independent effect of TLR on the primary outcome. TLR occurred in 160 patients (16.3%) and was an independent predictor of the primary end point (hazard ratio 2.8, 95% confidence interval 1.7 to 4.5). This association was significant for sirolimus-eluting stents and bare metal stents. TLR was also associated with an increased risk of subsequent stent thrombosis and nontarget vessel revascularization. Intracoronary brachytherapy in the TLR group was associated with an increased risk of cardiac death or MI. In conclusion, restenosis requiring TLR was associated with an increased risk of cardiac death or MI occurring at TLR and during the subsequent 5 years.

Drug-Eluting Stents in Animals and Patients

Four legs good, two legs better. — —George Orwell, Animal Farm, 1945 Since the earliest use of coronary stents for treating symptomatic coronary stenosis, maintaining patent arteries after treatment has remained an elusive goal. Although the first bare metal stents opened stenotic arteries, they injured the arterial wall. The buildup of intimal scar tissue caused restenosis, a frustrating problem for prevention or treatment. After a dozen years of research, however, drug-eluting stents were developed; armed with polymer coating and paclitaxel or sirolimus, they prevented restenosis and were hailed as a major therapeutic breakthrough. Article see p 141 Not long afterward, however, questions about the safety and efficacy of drug-eluting stents surfaced as reports of late stent thrombosis began to appear.1,2 Cardiologists wondered if prevention of restenosis was always a good thing. If no protective cellular layer formed over the struts of the drug-eluting stent—even months or years after implantation—would thrombus develop on the exposed metal scaffolding or other damaged or inflamed areas on the blood vessel wall? Over months or years, would progressive inflammation or late “catchup” tissue growth cause drug-eluting stents to lose their early advantage over bare metal stents? The pendulum in this debate has swung back and forth as clinical trials first raised concern about increased thrombosis and then later quelled our fears as our understanding of how drug-eluting stents work in real life has matured. An important issue has been the increased use of stents in patients with more complex coronary and other disorders, raising the question of whether the established standards of safety and efficacy still apply. Answers for these challenging questions have come from 2 worlds: clinical studies of patients with stents …

Impact of Target Lesion and Nontarget Lesion Cardiac Events on 5-Year Clinical Outcomes After Sirolimus-Eluting or Bare-Metal Stenting

We sought to compare patient-oriented outcomes related to target vessel or nontarget vessel events for sirolimus-eluting stents (SES) versus bare-metal stents. SES significantly reduce restenosis but the influence of reduced restenosis on overall patient-oriented outcome has not been reported. The study population included 1,057 patients randomized in the SIRIUS (Sirolimus-Eluting Stent in De Novo Native Coronary Lesions) study and followed clinically for 5 years. The primary end point was a composite of all-cause mortality, any myocardial infarction, or any repeat revascularization. In secondary analyses, myocardial infarction and repeat revascularization events attributed to the target vessel or a nontarget vessel were compared by stent type. Patients with an SES were more likely to be free from the primary composite end point at 5 years (60.4% vs. 47.8%, p < 0.001) chiefly due to a sustained reduction in target lesion revascularization for SES (cumulative incidence: 12.5% vs. 28.8%, p < 0.001). There was no difference in the cumulative incidence of myocardial infarction or revascularization attributed to remote segments of the target vessel. Events attributed to the nontarget vessel were frequent and not different for SES versus bare-metal stents (25.7% vs. 25.8%). The benefit of SES over bare-metal stents for reduced target lesion revascularization is maintained for 5 years. Remote coronary segments of the target vessel and nontarget vessel remain an important cause of future adverse events despite sustained restenosis benefit.

Five-Year Follow-Up After Sirolimus-Eluting Stent Implantation: Results of the SIRIUS (Sirolimus-Eluting Stent in De-Novo Native Coronary Lesions) Trial

The aim of this study was to examine the 5-year clinical safety and efficacy outcomes in patients enrolled in the SIRIUS (Sirolimus-Eluting Stent in De-Novo Native Coronary Lesions) trial.The SIRIUS trial was a double-blinded randomized study that demonstrated that sirolimus-eluting stents (SES) significantly improved angiographic results (at 8 months) and clinical outcomes (at 9 and 12 months) compared with bare-metal stents (BMS).Patients (n = 1,058) with de novo native coronary artery lesions were randomized to either SES (n = 533) or control BMS (n = 525) and were followed for 5 years.Between 1 and 5 years, additional clinical events were similarly distributed among the sirolimus and control groups. At 5 years, in sirolimus versus control patients, target lesion revascularization was 9.4% versus 24.2% (p < 0.001) and major adverse cardiovascular events and target vessel failure rates were 20.3% versus 33.5% and 22.5% versus 33.5%, respectively (p < 0.0001 for both). There were no significant differences in death, myocardial infarction, and nontarget lesion revascularization. No significant differences were observed in the cumulative incidence of stent thrombosis for sirolimus versus control patients with either protocol-derived (1.0% vs. 0.8%) or Academic Research Consortium definitions (3.9% vs. 4.2%).In patients with noncomplex coronary artery disease, clinical outcomes 5 years after implantation of SES continue to demonstrate significant reduction in the need for repeat revascularization, with similar safety (death and myocardial infarction) compared with BMS, without evidence for either disproportionate late restenosis or late stent thrombosis.

Abstract 2564: No Late and no Very Late Stent Thrombosis with a Drug-Eluting Stent of the Second Generation: 2 Years Results from the Randomized NOBORI-I Trial

Background: Late (after 30 days to 1 year) and very late (after 1 year) stent thrombosis is a continuous concern for drug-eluting stents (DES) of the first generation. These stents are characterized by their durable polymer and a ,,360 degree“ elution of the antiproliferative drug not only into the vessel wall, but also into the blood stream. Therefore, the second generation Nobori stent was developed with a biodegradable polymer and a drug elution restricted only to the vessel wall (abluminal coating). The drug, Biolimus A9, is a potent antiproliferative and antiinflammatory Limus derivative. Methods: The NOBORI-I trial was a prospective randomized study designed to compare the Nobori stent with the Taxus stent (2:1) in pats with single de-novo native coronary lesions, a vessel diameter of 2.5–3.5 mm and a lesion length below 25 mm. Predilatation was required. The primary endpoint was in-stent late lumen loss (LL) at 9 months. The study was designed as a noninferiority trial. 363 pats were enrolled in 29 sites in Europe, Asia and Australia. Clopidogrel (in addition to ASA) was recommended for at least 6 months. Results: With an in-stent LL of 0.12 mm in the Nobori and 0.33 mm in the Taxus group (p &lt;0.001) the primary endpoint was reached, with a significant result also for superiority. The results for late and very late stent thrombosis are depicted in the table . Dual antiplatelet therapy was present at one year in 52% of the pats in the Nobori and in 55% of the pats in the Taxus group. After 2 years, it was maintained in 25% of the Nobori and in 20% of the Taxus pats. Conclusions: As compared to a DES of the first generation with a durable polymer and circumferential drug release, the second generation Nobori stent with its biodegradable polymer and a drug-elution restricted to the vessel wall seems to be safer. Due to the limited power of this study regarding safety, higher number of patients are needed to corrobarate these promising findings.

Safety and Efficacy of the 2.25-mm Sirolimus-Eluting Bx Velocity Stent in the Treatment of Patients With De Novo Native Coronary Artery Lesions: the SIRIUS 2.25 Trial

Smaller reference vessel diameter is a recognized determinant of in-stent restenosis. The SIRIUS 2.25 trial was a prospective, nonrandomized study including 100 patients (mean age 63.4 years; 64% men, 40% with diabetes mellitus) assessing the safety and efficacy of the 2.25-mm sirolimus-eluting Bx Velocity stent in patients with de novo native coronary lesions. Using propensity score matching for gender, diabetes mellitus, left anterior descending artery target vessel, lesion length, and reference vessel diameter, the outcomes were compared with historical control groups (angioplasty and Palmaz-Schatz stent arms from the STRESS/BENESTENT I/II trials and the Bx Velocity bare metal stent arm from the RAVEL and SIRIUS trials having a reference vessel diameter <3 mm). Use of the 2.25-mm sirolimus-eluting Bx Velocity stent was associated with a high rate of procedural success (97%) and a low rate of in-hospital major adverse cardiac events (2%). The primary end point, 6-month in-lesion binary angiographic restenosis, occurred less frequently in patients treated with the 2.25-mm sirolimus-eluting Bx Velocity stent than in each of 3 historical controls (16.9% vs 30.6%, p = 0.12; 36.5%, p <0.001; 45.9%, p <0.001, respectively). This translated into lower rates of 6-month target lesion revascularization in the 2.25-mm sirolimus-eluting Bx Velocity stent group (4.0% vs 15.0% in each of 3 control groups, p = 0.01 to <0.001). By multivariate analysis, in-lesion binary restenosis was predicted by multiple implanted stents (odds ratio 10.4, p = 0.002). Four of 13 patients who developed restenosis (30.8%) had a diffuse pattern of restenosis. In the long lesion tertile (mean lesion length 19.5 mm), the in-lesion binary restenosis rate was 27.6%. In conclusion, use of the 2.25-mm sirolimus-eluting Bx Velocity stent was safe and provided favorable 6-month clinical outcomes. Use of multiple stents (in longer lesions) was an independent predictor of in-lesion restenosis.

Two-Year Outcomes After Sirolimus-Eluting Stent Implantation: Results From the Sirolimus-Eluting Stent in de Novo Native Coronary Lesions (SIRIUS) Trial

The purpose of this study was to examine the two-year clinical outcomes in patients enrolled in the Sirolimus-Eluting Stent in De Novo Native Coronary Lesions (SIRIUS) study. The SIRIUS study was a double-blinded randomized study which demonstrated that sirolimus-eluting stents (SES) significantly improved angiographic results (at 8 months) and clinical outcomes (at 9 and 12 months) compared with bare-metal stents (BMS). Patients with de novo native coronary artery lesions randomized to either SES (533 patients) or control BMS (525 patients) were followed for two years. Between one and two years, there were infrequent additional clinical events that were equally distributed between the sirolimus and control groups. After two years, target lesion revascularization was 5.8% and 21.3% in SES and control patients, respectively (p < 0.001), and major adverse cardiovascular events and target vessel failure rates were 10.1% versus 24.4% and 12.0% versus 26.7%, respectively (p < 0.0001 for both). There were no differences in death, myocardial infarction, and stent thrombosis between the two groups. Clinical outcomes two years after implantation of SES continue to demonstrate significant reduction in the need for repeat target lesion (and vessel) revascularization compared with BMS without evidence for either disproportionate late restenosis or late stent thrombosis.