Biomedical subjects
Publications and source records attributed to Martin B Leon.
Explore the source record for details and available documents.
OBJECTIVES: This trial examined the relative clinical efficacy, angiographic outcomes, and safety of zotarolimus-eluting coronary stents (ZES) with a phosphorylcholine polymer versus sirolimus-eluting stents (SES). BACKGROUND: Whether a cobalt-based alloy stent coated with the novel antiproliferative agent, zotarolimus, and a phosphorylcholine polymer may provide similar angiographic and clinical benefit compared with SES is undetermined. METHODS: A prospective, multicenter, 3:1 randomized trial was conducted to evaluate the safety and efficacy of ZES (n = 323) relative to SES (n = 113) in 436 patients undergoing elective percutaneous revascularization of de novo native coronary lesions with reference vessel diameters between 2.5 mm and 3.5 mm and lesion length > or =14 mm and < or =27 mm. The primary end point was 8-month angiographic in-segment late lumen loss. RESULTS: Angiographic in-segment late lumen loss was significantly higher among patients treated with ZES compared with SES (0.34 +/- 0.44 mm vs. 0.13 +/- 0.32 mm, respectively; p < 0.001). In-hospital major adverse cardiac events were significantly lower among patients treated with ZES (0.6% vs. 3.5%, p = 0.04). In-segment binary angiographic restenosis was also higher in the ZES cohort (11.7% vs. 4.3%, p = 0.04). Total (clinically and non-clinically driven) target lesion revascularization rates at 9 months were 9.8% and 3.5% for the ZES and SES groups, respectively (p = 0.04). However, neither clinically driven target lesion revascularization (6.3% zotarolimus vs. 3.5% sirolimus, p = 0.34) nor target vessel failure (12.0% zotarolimus vs. 11.5% sirolimus, p = 1.0) differed significantly. CONCLUSIONS: Compared with SES, treatment with a phosphorylcholine polymer-based ZES is associated with significantly higher late lumen loss and binary restenosis at 8-month angiographic follow-up. (The Endeavor III CR; http://clinicaltrials.gov/ct/show/NCT00265668?order=1?).
AIMS: Although drug-eluting stents have assumed a dominant role in interventional cardiology, concern has been raised about the potential for long-term adverse outcomes, including death. The aim of the present study was to compare the incidence and cause of death between patients who received sirolimus-eluting or bare metal stents. METHODS AND RESULTS: An integrated analysis was performed on 1748 patients enrolled in four prospective double-blind trials that randomly assigned patients to receive either a sirolimus-eluting or a bare metal stent for treatment of a single de novo coronary stenosis. During a mean follow-up of 2.6+/-0.6 years, 64 patients (3.7%) died. Total mortality was 3.2% among 870 bare metal stent patients and 4.1% among 878 sirolimus-eluting stent patients (P=0.37); there was no difference in cardiac mortality (1.4 vs. 1.3%; P=0.55) or causes of death between these two groups. The predominant cause of death was non-cardiac. Cardiac death was most frequently assigned owing to unwitnessed death. Death due to acute myocardial infarction, congestive heart failure, and stent thrombosis occurred infrequently. CONCLUSION: At a mean follow-up of 2.6 years in percutaneous coronary intervention patients, the predominant cause of death was non-cardiac. There was no significant difference in either the frequency or the cause of death with implantation of either sirolimus-eluting or bare metal stents.
The neointimal hyperplasia (IH) distribution pattern of in-stent restenotic lesions after sirolimus-eluting stent (SES) implantation has not been well described. We identified 48 in-stent restenotic lesions (41 patients) after SES implantation and performed volumetric intravascular ultrasound analyses. Lumen area, stent area, and IH area at the minimal lumen area site were 2.7 +/- 1.0, 5.4 +/- 1.9, and 2.7 +/- 1.4 mm(2), respectively. IH area at the minimal lumen site was larger in the group with a stent area > or =5.0 mm(2) than the group with a stent area <5.0 mm(2) (3.7 +/- 1.3 vs 1.9 +/- 0.8 mm(2), p <0.001). There were fewer visualized stent struts in lesions with a minimum stent area > or =5.0 mm(2) at the minimum lumen site compared with those with a stent area <5.0 mm(2) (0.69 +/- 0.25 vs 0.83 +/- 0.16, p = 0.04). When we compared lesions in patients with diabetes mellitus with patients without diabetes, minimum lumen areas, percent IH at minimal lumen area, percent IH, and neointima-free stent length were identical. In conclusion, (1) lesions without SES underexpansion at the minimum lumen site had more IH and greater nonuniform stent strut distribution compared with restenotic SESs that were underexpanded, and (2) the IH response did not appear to be more aggressive in patients with diabetes mellitus than in those without diabetes mellitus.
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.
This report describes angiographic findings of the first-in-human evaluation of the Biolimus A9 drug-eluting stent (Biolimus stent) in the treatment of noncomplex coronary lesions. In total, 120 patients with 122 de novo coronary lesions (2.75- to 4.00-mm vessels, < or = 24-mm lesion length) were prospectively randomized in a 2:1 ratio to receive the Biolimus stent (n = 80, 82 lesions) or the control uncoated stent (n = 40). Baseline lesion and angiographic characteristics were similar between groups. At 6-month follow-up, late lumen loss was significantly decreased with the Biolimus stent in the stent (0.26 +/- 0.43 vs 0.74 +/- 0.45 mm, p < 0.001) and in the segment (0.14 +/- 0.45 vs 0.40 +/- 0.41 mm, p = 0.004). In-stent restenosis was 3.9% in the Biolimus stent group versus 7.7% in the control group (p = 0.40). There was no exaggerated hyperplasia at the proximal and/or distal edge of the stent.
We investigated the fate of postprocedural incomplete stent apposition (ISA) after sirolimus-eluting stent (SES) implantation by evaluating long-term intravascular ultrasound findings in 168 consecutive patients (182 de novo lesions). Postprocedural ISA was defined as > or = 1 stent strut that was clearly separated from the vessel wall with evidence of blood speckle behind the strut without overlapping a side branch. After SES implantation, there were 61 ISA sites in 46 stents in 31 patients (23 at the proximal edge, 7 at the distal edge, and 31 within the stent body). There were no clinical, procedural, or intravascular ultrasound measurement differences between patients and lesions with versus without ISA. At follow-up, 15 acute ISA sites (25%) in 11 patients completely resolved and 40 sites (75%) in 20 patients persisted, although 32 of 46 persisting ISA sites (70%) decreased. There was a greater decrease in effective lumen area and a greater increase in peristent plaque area in the complete-resolution group than in the persistent-ISA group. No lesion developed stent thrombosis or in-stent restenosis (angiographic diameter stenosis > 50%). Six acute ISA sites were also associated with new, late acquired ISA, only 1 of which resulted in aneurysm formation. Although most ISAs after SES implantation do not resolve completely, the incidence of restenosis or thrombosis is not affected.
The everolimus-eluting stent (EES) has been shown to significantly decrease neointimal proliferation at 6 months compared with the bare metal stent (BMS) in patients with de novo coronary lesions. We report mid-term outcomes based on different vessel sizes in the combined FUTURE I and II trials. In the prospective, randomized, FUTURE I trial (single center) and expanded FUTURE II trial (multicenter), 106 patients (107 lesions) were randomized to EESs (n = 49 lesions) or BMSs (n = 58 lesions). Patients were categorized into 3 groups based on preprocedure reference diameter as assessed by quantitative coronary angiography (small vessel < 2.75 mm, medium vessel 2.75 to 3.25 mm, and large vessel > 3.25 mm). At 6-month follow-up, EESs decreased in-stent late lumen loss (decreased rate range of 78% to 94%), resulting in significantly larger minimum lumen area as assessed by intravascular ultrasound (increased range of 34% to 42%) compared with the BMS across all vessel sizes. There were no cases of in-stent restenosis with EESs at any vessel size but 8 cases with BMSs (5 in small vessels). No stent thrombosis, aneurysm formation, or late stent incomplete apposition was observed in any group. The EES appears to be effective for treatment of de novo coronary lesions in decreasing neointimal proliferation at 6-month follow-up compared with BMSs, regardless of vessel size.
Angiographic studies have shown that lesions preceding nonfatal acute events are usually not hemodynamically significant. This has led to the concept that plaque ruptures occur at minimal disease sites. We used intravascular ultrasound to create a prerupture "profile" of unstable (vulnerable) plaques. We analyzed 112 ruptured plaques detected by intravascular ultrasound. Reference and lesion external elastic membrane (EEM) and lumen areas were measured to calculate prerupture estimates of plaque area, plaque burden (plaque/EEM area), eccentricity, area stenosis, and remodeling. The narrowest coefficients of variance were for lesion EEM area, maximum plaque thickness, and plaque burden, reference lumen area, and remodeling index (coefficients of variance 0.29, 0.25, 0.12, 0.29, and 0.18, respectively); conversely, there was great variability in measurements of calcification and lumen compromise (minimum lumen area and area stenosis). When using the 5 variables with the narrowest coefficient of variance, we found that 67% of ruptured plaques fit all of following 10th or 90th percentile parameters (> 14.3 mm2 lesion EEM area, > 8.1 mm2 reference lumen area, > 1.6 mm maximum lesion plaque thickness, > 0.63 lesion plaque burden, and > 0.87 remodeling index). Further, 89% of ruptured plaques fit 4 of 5 parameters and 96% fit 3 of 5 parameters. In conclusion, plaque ruptures do not occur at minimal disease sites. Rather, vulnerable (rupture-prone) plaques predictably have significant plaque accumulation and remodeling and occur in larger arteries. It is only the degree of lumen compromise that is variable and often insignificant.
Coronary artery perforation is a rare, but dreaded, complication of percutaneous coronary intervention. Conventional treatment, including reversal of anticoagulation and prolonged balloon inflation, is associated with a high incidence of death, Q-wave myocardial infarction, and emergency coronary bypass surgery. Although a number of case reports have demonstrated the feasibility of sealing coronary perforations with synthetic material-covered stent grafts, the efficacy of this treatment has not been reported in a large, multicenter series. We used a retrospective international registry to examine the outcomes of the polytetrafluoroethylene-coated JOSTENT coronary stent graft (CSG) in 41 cases of coronary perforations. Perforations were relatively severe: 16.7% Ellis grade 1, 54.2% grade 2, and 29.1% grade 3. Of the 41 patients, > 1/3 (n = 14) experienced life-threatening complications before stent graft implantation, including pericardial tamponade (12.2%), cardiogenic shock (9.8%), and cardiac arrest (2.4%). A total of 52 CSGs were used to treat the 41 perforations (mean 1.3 per lesion). All CSGs were placed successfully, with 92.9% of the perforations sealed completely and 7.1% partially. One patient developed abrupt vessel closure after CSG deployment, resulting in an overall procedure success rate of 96.4%. No in-hospital Q-wave myocardial infarctions, emergency coronary bypass surgeries, or deaths resulted. The CSG may be a reliable and highly effective treatment option for sealing coronary perforations complicating percutaneous coronary interventions.
OBJECTIVES: The purpose of this research was to determine the relative safety and efficacy of multiple (> or =2) overlapping Cypher sirolimus-eluting stents (SES) (Johnson & Johnson, New Brunswick, New Jersey). BACKGROUND: Overlapping coronary stents are common. The periprocedural and late clinical and angiographic consequences of overlapped coronary stents are not clearly defined, particularly for drug-eluting stents. METHODS: All patients enrolled into five clinical trials of the SES were analyzed. Three of these trials were prospective randomized comparisons of the SES to the bare-metal stent (BMS), and two were prospective non-randomized trials of SES-treated patients with historical controls. All clinical and angiographic outcomes in overlap-stent-treated patients were compared by stent type and with single-stent-treated patients for the same stent device. RESULTS: In all, 575 patients with stent overlap (337 SES, 238 BMS) and 1,162 patients with single stents (697 SES, 465 BMS) were analyzed. Stent overlap was associated with a greater late lumen loss in stent and more frequent angiographic restenosis regardless of stent type. Among overlap-stent-treated patients, the SES provided similar magnitude of restenosis benefit as observed for single-stent-treated patients. Overlapped SES was not associated with an increase in myocardial infarction. CONCLUSIONS: The strategy of SES overlap, when required, is both safe and efficacious in reducing restenosis with no increase in the incidence of myocardial infarction or major adverse cardiovascular events, when compared with a bare metal coronary stent prosthesis.
OBJECTIVES: To address the safety and efficacy of drug-eluting stents (DES) in the treatment of intermediate lesions, we performed a pooled analysis of four randomized DES versus bare-metal stent (BMS) trials and assessed outcomes among patients with intermediate lesions. BACKGROUND: Before the introduction of DES, intermediate coronary lesions were commonly managed based on physiologic or anatomic assessment of lesion severity. The DES may challenge this paradigm. METHODS: The study population involved 167 of 2,478 randomized patients (6.7%) with intermediate lesions (diameter stenosis <50% [mean 44%] by quantitative coronary angiography) from the Sirolimus-coated Bx Velocity Balloon Expandable Stent in the Treatment of Patients with De Novo Coronary Artery Lesions (SIRIUS), TAXUS-IV, and the First and Second First Use to Underscore Restenosis Reduction with Everolimus (FUTURE-I and -II) trials. End points examined included early (in-hospital and 30-day) and late (1-year) major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis, and follow-up angiographic restenosis. RESULTS: Patients with intermediate lesions randomized to DES versus BMS had low rates of 30-day MACE (1.1% vs. 4.0% respectively; p = 0.22). At one-year follow-up, patients treated with DES versus BMS had similar rates of cardiac death (0% vs. 2.7%, respectively; p = 0.11) and MI (3.4% vs. 5.4%; p = 0.49) but markedly lower rates of TVR (3.4% vs. 20.3%; p = 0.0004), MACE (5.6% vs. 25.4%; p = 0.0003), and binary angiographic restenosis (1.8% vs. 34.0%; p < 0.0001). No patient in either group developed stent thrombosis. CONCLUSIONS: Compared with BMS, treatment of intermediate lesions with DES appears safe and results in a marked reduction in clinical and angiographic restenosis. The efficacy of DES may require a reevaluation of current treatment paradigms for intermediate lesions.
Prospective follow-up at 2 years was obtained for 98.7% of the pooled 1,510 patients enrolled in SIRIUS, E-SIRIUS and C-SIRIUS, 3 randomized controlled trials that compared sirolimus-eluting stents (SESs) with bare metal stents (BMSs) to treat long stenoses in small coronary arteries. By 720 days, clinically driven target lesion revascularizations were performed in 5.7% of patients with SESs versus 22.6% of patients with BMSs (risk ratio 0.25, 95% confidence interval 0.18 to 0.35, p <0.001). Of these, late target lesion revascularization (from 271 to 720 days) was performed in 12 patients who received SESs (1.6%) compared with 37 patients with BMSs (4.9%) (risk ratio 0.32, 0.17 to 0.61, p <0.001). Stent thromboses occurred in 7 of 758 patients with SESs (0.9%, 4 subacute, 3 late) and 5 of 752 patients with BMSs (0.7%, 1 subacute, 4 late) (risk ratio 1.39, 95% confidence interval 0.44 to 4.36, p = 0.774). The Kaplan-Meier estimate of freedom from major cardiac adverse events was 89.3% for patients with SESs versus 73.4% for patients with BMSs (p <0.001). This analysis demonstrates the sustained efficacy and safety of sirolimus-eluting stents at 2 years, characterized by a persistent significant benefit in freedom from repeat revascularization compared with BMSs and a low risk of late stent thrombosis, not different from BMSs.
Explore the source record for details and available documents.
Although clinical outcomes after sirolimus-eluting stents (SESs) have been previously described ("primary" success rates), the fate of patients whose SES implantation fail and who require ischemia-driven target lesion revascularization is poorly understood. The SIRIUS trial is a prospective, randomized, clinical trial that includes 533 evaluable patients with SESs. Twenty-two of these patients had adjudicated ischemia-driven target lesion revascularization (4.1%) within the first year of follow-up and comprised the study population of this analysis. Of these patients, 11 (50%) had diabetes, and restenotic lesions were focal and located at the proximal stent edge in 91% and 73% of patients, respectively. Restenosis was treated with bare metal stent implantation, balloon dilatation, or intravascular brachytherapy in 82%, 13.5%, and 4.5% of patients, respectively. At 1-year follow-up after the first recurrence (2-year follow-up after the index procedure), only 5 of these patients (23%) required a second repeat revascularization procedure. Risk factors for a second recurrence after treatment of SES restenosis were female gender, long lesions that required long stents at the index procedure, and an early first recurrence. In conclusion, SES failure treated with traditional percutaneous coronary intervention yielded good outcome at 1-year follow-up (secondary failure rate only 23%), perhaps due to the focal nature of the SES restenotic lesion. Future studies should evaluate other methods, including drug-eluting stents, to further optimize the outcome of treatment of SES failures.
Although the success rates of percutaneous coronary intervention of chronic total occlusions (CTOs) have improved, morphologic features are not well known. We analyzed experience at 4 centers where intravascular ultrasound (IVUS) was performed in 67 native artery CTO lesions (mean CTO duration 6.3 months) just after the lesion was crossed with a guidewire (n = 7) or after dilatation with a 1.5-mm (n = 46) or 2.0-mm (n = 14) balloon. IVUS detected calcium somewhere in the CTO in 96%; however, only 68% had mild calcium. IVUS identified a proximal end of the CTO in all lesions, but a distal end of the CTO in only 50%. An intramural hematoma was observed in 34% of CTOs, suggesting that the guidewire frequently entered the medial space during successful recanalization. CTOs were longer, vessel area was smaller, and total calcium index was greater in lesions with hematomas (p = 0.003, 0.05, and 0.03, respectively). Inadequate reflow after the procedure was observed in 9% and was associated with longer lesions and intralesional calcium. CTO length as measured with angiography was shorter than the length as measured with IVUS (p = 0.02). Calcium was detected on the angiogram in 61% (p = 0.054 vs IVUS). Most typical angiographic findings associated with a low rate of procedural success were not associated with different IVUS morphologies. In conclusion, CTO lesions had multiple small calcium deposits, intramural hematomas were common and were indicative of guidewire penetration into the medial space during the CTO procedure, especially in long calcified lesions in smaller vessels, and inadequate reflow after the procedure was correlated with more complex CTO morphology.
Previous studies have reported differences in interventional complication rates that depend on saphenous vein graft (SVG) lesion location. However, little is known about morphologic differences between lesions in different SVG locations. We evaluated preintervention intravascular ultrasound (IVUS) images of 75 de novo SVG lesions (aorto-ostial, n = 15; shaft, n = 60) in 63 patients. IVUS data were measured at the minimal lumen area and at 2 proximal and 2 distal references. Positive remodeling was defined as a lesion site SVG area that was larger than the average of the 2 distal references. Shaft lesions more often contained soft plaque (60.0% vs 26.7%, p = 0.02). Minimal lumen areas were identical (4.5 +/- 2.9 vs 4.3 +/- 1.5 mm2, p = 0.3); however, plaque burden at the minimal lumen area was greater in shaft locations (79.3 +/- 9.4% vs 72.1 +/- 9.2%, p = 0.01). The frequency of positive remodeling in shaft versus aorto-ostial lesions was 70.2% versus 26.7% (p = 0.002). SVG shaft lesions have more soft plaque and larger plaque burdens and undergo positive remodeling more frequently than SVG aorto-ostial lesions. These IVUS differences may account for some of the location-specific differences in interventional complications.
The "crush technique" has been proposed as an alternative approach to treat bifurcation lesions because of its predictability and high procedural success rate. However, few data are available regarding its safety and long-term efficacy. We report the long-term clinical outcomes of patients with coronary bifurcation lesions treated with sirolimus-eluting stents using the crush technique. From April 2003 to May 2004, 120 patients with coronary bifurcation lesions were treated with sirolimus-eluting stents using the crush technique. Six months of clinical follow-up was completed in 95.8% of patients. Mean patient age was 64 years; 36% had diabetes mellitus, and the left anterior descending artery/diagonal was the most frequent bifurcation location (69%). Final kissing balloon inflation was performed in 87.5% of patients. Compared with the main vessel, side branch lesions were shorter, with a smaller reference diameter and final in-stent minimum lumen diameter. Procedural success was achieved in 97.5%. At 30 days of follow-up, 1 patient had died of noncardiac causes and 2 patients (1.7%) had subacute stent thrombosis. At 6 months of follow-up, target lesion revascularization was required in 13 patients (11.3%), all of whom had focal restenosis predominantly at the side branch ostium. In conclusion, the crush technique with final kissing balloon inflation can be safely used by experienced operators to treat highly complex bifurcation lesions with sirolimus-eluting stents. The safety profile of this technique is similar to that of other bifurcation stenting techniques reported thus far. Nonetheless, despite the excellent patency rates of the main vessel, the need for revascularization at the ostium of the side branch was not fully eliminated.