A prospective natural-history study of coronary atherosclerosis.

BACKGROUND: Atherosclerotic plaques that lead to acute coronary syndromes often occur at sites of angiographically mild coronary-artery stenosis. Lesion-related risk factors for such events are poorly understood. METHODS: In a prospective study, 697 patients with acute coronary syndromes underwent three-vessel coronary angiography and gray-scale and radiofrequency intravascular ultrasonographic imaging after percutaneous coronary intervention. Subsequent major adverse cardiovascular events (death from cardiac causes, cardiac arrest, myocardial infarction, or rehospitalization due to unstable or progressive angina) were adjudicated to be related to either originally treated (culprit) lesions or untreated (nonculprit) lesions. The median follow-up period was 3.4 years. RESULTS: The 3-year cumulative rate of major adverse cardiovascular events was 20.4%. Events were adjudicated to be related to culprit lesions in 12.9% of patients and to nonculprit lesions in 11.6%. Most nonculprit lesions responsible for follow-up events were angiographically mild at baseline (mean [±SD] diameter stenosis, 32.3±20.6%). However, on multivariate analysis, nonculprit lesions associated with recurrent events were more likely than those not associated with recurrent events to be characterized by a plaque burden of 70% or greater (hazard ratio, 5.03; 95% confidence interval [CI], 2.51 to 10.11; P<0.001) or a minimal luminal area of 4.0 mm(2) or less (hazard ratio, 3.21; 95% CI, 1.61 to 6.42; P=0.001) or to be classified on the basis of radiofrequency intravascular ultrasonography as thin-cap fibroatheromas (hazard ratio, 3.35; 95% CI, 1.77 to 6.36; P<0.001). CONCLUSIONS: In patients who presented with an acute coronary syndrome and underwent percutaneous coronary intervention, major adverse cardiovascular events occurring during follow-up were equally attributable to recurrence at the site of culprit lesions and to nonculprit lesions. Although nonculprit lesions that were responsible for unanticipated events were frequently angiographically mild, most were thin-cap fibroatheromas or were characterized by a large plaque burden, a small luminal area, or some combination of these characteristics, as determined by gray-scale and radiofrequency intravascular ultrasonography. (Funded by Abbott Vascular and Volcano; ClinicalTrials.gov number, NCT00180466.).

Does clinical presentation affect outcome among patients with acute coronary syndromes undergoing percutaneous coronary intervention? Insights from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree study.

BACKGROUND: In some prior studies, patients with ST-elevation myocardial infarction (STEMI) as compared with patients with non-STEMI (NSTEMI) tended to have a higher early mortality but similar long-term outcomes. We compared the angiographic and intravascular ultrasound (IVUS) characteristics of patients with STEMI and NSTEMI in the PROSPECT study to evaluate the independent prognostic value of clinical presentation on long-term outcome. METHODS: After successful revascularization, patients had 3-vessel quantitative coronary angiography, gray scale, and radiofrequency intravascular ultrasound (IVUS) imaging. The primary end point was the occurrence of major adverse cardiac events (MACE) (cardiac death, myocardial infarction, or rehospitalization for unstable or progressive angina). RESULTS: There were 211 patients (31.6%) with STEMI and 457 (68.4%) with NSTEMI. Patients with STEMI and NSTEMI had similar angiographic and IVUS morphologic characteristics. At 3 years, MACE occurred in 22.1% and 19.6%, respectively (hazard ratio [HR] 1.16 [0.81, 1.68], P = .42). There was a higher overall mortality (HR 2.16 [0.94, 4.99], P = .06) and a significantly higher incidence of probable stent thrombosis (HR 4.34 [1.09, 17.36], P = .02) in the STEMI cohort. There were no significant differences between the 2 groups with respect to events related to culprit or to nonculprit lesions. ST-elevation myocardial infarction presentation was not an independent predictor of 3-year MACE (HR 1.14 [0.77, 1.67], P = .52). CONCLUSION: Patients with STEMI and NSTEMI did not differ with respect to residual nonculprit lesion angiographic or IVUS characteristics and had similar rates of MACE at 3 years, without late "catch-up" in NSTEMI. However, probable stent thrombosis and mortality were higher in the STEMI cohort.

An intravascular ultrasound appraisal of atherosclerotic plaque distribution in diseased coronary arteries.

BACKGROUND: The assumption that atherosclerosis accumulates in the proximal coronary arteries and that distal segments are spared has yet to be systematically shown in vivo. METHODS: We used intravascular ultrasound to analyze complete proximal, mid, and distal segments from 75 diseased left anterior descending arteries (LADs) and 61 diseased right coronary arteries (RCAs) (including either the posterolateral [PLA; n = 38] or posterior descending artery [PDA; n = 23]) to document that distal coronary arteries are more often free of disease vs proximal vessels. External elastic membrane, lumen, and plaque and media areas were measured every 0.4 mm (median), and plaque burden (plaque and media/external elastic membrane) and percentage of normal (plaque and media thickness <0.3 mm) cross sections/segment were determined. RESULTS: Left anterior descending artery plaque was heaviest in proximal and mid segments, diminishing significantly in distal segments; plaque burden was 46% ± 9% in proximal, 39% ± 8% in mid, and 31% ± 9% in distal LAD (P < .0001), with 93% (median) of distal LAD cross sections being normal compared with 21% of mid and 0% of proximal cross sections (P < .0001). Right coronary artery plaque gradient was less pronounced vs the LAD; plaque burden was 37% ± 13% in proximal, 40% ± 10% in mid, and 36% ± 10% in distal RCA, followed by 31% ± 11% in PDA and 33% ± 10% in PLA. This was supported by the median percentage of normal cross sections/segment: 0% proximal, 0% mid, and 23% distal RCA sections plus 100% PDA and 48% PLA sections. CONCLUSIONS: Intravascular ultrasound data indicated a proximal-to-distal LAD plaque gradient; significant disease was uncommon in the distal LAD. Conversely, the proximal-to-distal RCA plaque gradient was less distinct than the LAD, although disease in the PDA was still reduced compared with proximal segments.

Randomized comparison of everolimus-eluting and paclitaxel-eluting stents: two-year clinical follow-up from the Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) III trial.

BACKGROUND: In the prospective randomized Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) III trial, an everolimus-eluting stent (EES) compared with a widely used paclitaxel-eluting stent (PES) resulted in a statistically significant reduction in angiographic in-segment late loss at 8 months and noninferior rates of target vessel failure (cardiac death, myocardial infarction, or target vessel revascularization) at 1 year. The safety and efficacy of EES after 1 year have not been reported. METHODS AND RESULTS: A total of 1002 patients with up to 2 de novo native coronary artery lesions (reference vessel diameter, 2.5 to 3.75 mm; lesion length < or =28 mm) were randomized 2:1 to EES versus PES. Antiplatelet therapy consisted of aspirin indefinitely and a thienopyridine for > or =6 months. Between 1 and 2 years, patients treated with EES compared with PES tended to have fewer episodes of protocol-defined stent thrombosis (0.2% versus 1.0%; P=0.10) and myocardial infarctions (0.5% versus 1.7%; P=0.12), with similar rates of cardiac death (0.3% versus 0.3%; P=1.0) and target vessel revascularization (2.9% versus 3.0%; P=1.0). As a result, at the completion of the 2-year follow-up, treatment with EES compared with PES resulted in a significant 32% reduction in target vessel failure (10.7% versus 15.4%; hazard ratio, 0.68; 95% confidence interval, 0.48 to 0.98; P=0.04) and a 45% reduction in major adverse cardiac events (cardiac death, myocardial infarction, or target lesion revascularization; 7.3% versus 12.8%; hazard ratio, 0.55; 95% confidence interval, 0.36 to 0.83; P=0.004). Among the 360 patients who discontinued clopidogrel or ticlopidine after 6 months, stent thrombosis subsequently developed in 0.4% of EES patients versus 2.6% of PES patients (P=0.10). CONCLUSIONS: Patients treated with EES rather than PES experienced significantly improved event-free survival at a 2-year follow-up in the SPIRIT III trial, with continued divergence of the hazard curves for target vessel failure and major adverse cardiac events between 1 and 2 years evident. The encouraging trends toward fewer stent thrombosis episodes after 6 months in EES-treated patients who discontinued a thienopyridine and after 1 year in all patients treated with EES rather than PES deserve further study.

Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease: a randomized trial.

CONTEXT: A thin, cobalt-chromium stent eluting the antiproliferative agent everolimus from a nonadhesive, durable fluoropolymer has shown promise in preliminary studies in improving clinical and angiographic outcomes in patients with coronary artery disease. OBJECTIVE: To evaluate the safety and efficacy of an everolimus-eluting stent compared with a widely used paclitaxel-eluting stent. DESIGN, SETTING, AND PATIENTS: The SPIRIT III trial, a prospective, randomized, single-blind, controlled trial enrolling patients at 65 academic and community-based US institutions between June 22, 2005, and March 15, 2006. Patients were 1002 men and women undergoing percutaneous coronary intervention in lesions 28 mm or less in length and with reference vessel diameter between 2.5 and 3.75 mm. Angiographic follow-up was prespecified at 8 months in 564 patients and completed in 436 patients. Clinical follow-up was performed at 1, 6, 9, and 12 months. INTERVENTIONS: Patients were randomized 2:1 to receive the everolimus-eluting stent (n = 669) or the paclitaxel-eluting stent (n = 333). MAIN OUTCOME MEASURES: The primary end point was noninferiority or superiority of angiographic in-segment late loss. The major secondary end point was noninferiority assessment of target vessel failure events (cardiac death, myocardial infarction, or target vessel revascularization) at 9 months. An additional secondary end point was evaluation of major adverse cardiac events (cardiac death, myocardial infarction, or target lesion revascularization) at 9 and 12 months. RESULTS: Angiographic in-segment late loss was significantly less in the everolimus-eluting stent group compared with the paclitaxel group (mean, 0.14 [SD, 0.41] mm vs 0.28 [SD, 0.48] mm; difference, -0.14 [95% CI, -0.23 to -0.05]; P < or = .004). The everolimus stent was noninferior to the paclitaxel stent for target vessel failure at 9 months (7.2% vs 9.0%, respectively; difference, -1.9% [95% CI, -5.6% to 1.8%]; relative risk, 0.79 [95% CI, 0.51 to 1.23]; P < .001). The everolimus stent compared with the paclitaxel stent resulted in significant reductions in composite major adverse cardiac events both at 9 months (4.6% vs 8.1%; relative risk, 0.56 [95% CI, 0.34 to 0.94]; P = .03) and at 1 year (6.0% vs 10.3%; relative risk, 0.58 [95% CI, 0.37 to 0.90]; P = .02), due to fewer myocardial infarctions and target lesion revascularization procedures. CONCLUSIONS: In this large-scale, prospective randomized trial, an everolimus-eluting stent compared with a paclitaxel-eluting stent resulted in reduced angiographic late loss, noninferior rates of target vessel failure, and fewer major adverse cardiac events during 1 year of follow-up. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00180479.

Relationship between left main coronary artery plaque burden and nonleft main coronary atherosclerosis: results from the PROSPECT study.

OBJECTIVES: Whether the severity of left main coronary artery (LMCA) disease reflects LMCA and overall coronary atherosclerotic burden is not known. We aimed to assess nonculprit LMCA disease characteristics and the relationship with atherosclerosis in the rest of the coronary arteries as well as patient outcomes. PATIENTS AND METHODS: In the PROSPECT study, 697 patients with acute coronary syndromes underwent three-vessel gray-scale and radiofrequency intravascular ultrasound after percutaneous coronary intervention. RESULTS: Overall, 552 patients with adequate LMCA imaging were compared according to LMCA plaque burden. The tertile with the highest plaque burden in the LMCA had the smallest LMCA minimum lumen area (17.4, 14.2, 10.5, lowest through highest tertiles, respectively, P<0.0001) and the greatest percent necrotic core volume (2.8, 5.6, 9.5%, lowest through highest tertiles, respectively, P<0.0001). Furthermore, the tertile with the highest plaque burden was also significantly associated with the highest overall non-LMCA percent atheroma volume within the major epicardial arteries (48.3, 49.2, 50.8%, lowest through highest tertiles, respectively, P<0.0001). After adjusting for patient background, the LMCA plaque burden was independently associated with non-LMCA percent atheroma volume (P=0.003). Of the three PROSPECT predictors of future nonculprit major adverse cardiac events (MACE) (minimum lumen area≤4 mm, plaque burden≥70%, and virtual histology thin-cap fibroatheroma), the tertile with the highest LMCA plaque burden had the highest number of patients with at least one of three PROSPECT predictors (P=0.03). In multivariable model, though total atheroma volume (per 1%) was an independent predictor of all MACE [hazard ratio (95% confidence interval)=1.06 (1.01-1.11), P=0.02] and strong trend for non-culprit-related MACE [hazard ratio (95% confidence interval)=1.06 (1.00-1.13), P=0.06], plaque burden at LMCA was not (all MACE, P=0.90, non-culprit-related MACE, P=0.85). CONCLUSION: The severity of atherosclerosis in LMCA predicted the overall atherosclerotic plaque burden as well as the presence of high-risk plaques in the three major epicardial coronary arteries.

Internet Presentation of Departments of Pediatric Surgery in Germany and Their Compliance with Recommended Criteria for Promoting Services and Offering Professional Information for Patients.

Introduction The presentation of health institutions in the internet is highly variable concerning marketing features and medical information. We aimed to investigate the structure and the kind of information provided on the Web sites of all departments of pediatric surgery in Germany. Furthermore, we aimed to identify the degree to which these Web sites comply with internet marketing recommendations for generating business. Method The Web sites of all pediatric surgery units referred to as departments on the official Web site of the German Society of Pediatric Surgery (GSPS) were assessed. The search engine Google was used by entering the terms "pediatric surgery" and the name of the city. Besides general data eight content characteristics focusing on ranking, accessibility, use of social media, multilingual sites, navigation options, selected images, contact details, and medical information were evaluated according to published recommendations. Results A total of 85 departments of pediatric surgery were included. On Google search results 44 (52%) ranked number one and 34 (40%) of the department's homepages were accessible directly through the homepage link of the GSPS. A link to own digital and/or social media was offered on 11 (13%) homepages. Nine sites were multilingual. The most common navigation bar item was clinical services on 74 (87%) homepages. Overall, 76 (89%) departments presented their doctors and 17 (20%) presented other staff members with images of doctors on 53 (62%) and contact data access from the homepage on 68 (80%) Web sites. On 25 (29%) Web sites information on the medical conditions treated were presented, on 17 (20%) details of treating concepts, and on 4 (5%) numbers of patients with specific conditions treated in the own department per year. Conclusion We conclude that numerous of the investigated online presentations do not comply with recommended criteria for offering professional information for patients and for promoting services. Only less than one-third of the departments of pediatric surgery in Germany offer information about the medical conditions they treat. Features, which may influence the decision of patients and parents such as ranking, accessibility, use of social media, multilingual sites, navigation options, selected images, and contact information were differently lacking on many Web sites.

Predictors of Plaque Rupture Within Nonculprit Fibroatheromas in Patients With Acute Coronary Syndromes: The PROSPECT Study.

OBJECTIVES: The study sought to examine the relative importance of lesion location versus vessel area and plaque burden in predicting plaque rupture within nonculprit fibroatheromas (FAs) in patients with acute coronary syndromes. BACKGROUND: Previous studies have demonstrated that plaque rupture is associated with larger vessel area and greater plaque burden clustering in the proximal segments of coronary arteries. METHODS: In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study 3-vessel grayscale and radiofrequency-intravascular ultrasound was performed after successful percutaneous coronary intervention in 697 patients with acute coronary syndromes. Untreated nonculprit lesion FAs were classified as proximal (<20 mm), mid (20 to 40 mm), and distal (>40 mm) according to the distance from the ostium to the maximum necrotic core site. RESULTS: Overall, 74 ruptured FAs and 2,396 nonruptured FAs were identified in nonculprit vessels. The majority of FAs (73.6%) were located within 40 mm of the ostium, and the vessel area and plaque burden progressively decreased from proximal to distal FA location (both p < 0.001). In a multivariate logistic regression model, independent predictors for plaque rupture included the distance from the ostium to the maximum necrotic core site per millimeter (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.76 to 0.98; p = 0.02), plaque burden per 10% (OR: 2.05; 95% CI: 1.63 to 2.58; p < 0.0001), vessel area per mm(2) (OR: 1.14; 95% CI: 1.11 to 1.17; p < 0.0001), calcium (OR: 0.09; 95% CI: 0.05 to 0.18; p < 0.0001), and right coronary artery location (OR: 2.16; 95% CI: 1.25 to 3.27; p = 0.006). By receiver-operating characteristic analysis, vessel area correlated with plaque rupture stronger than either plaque burden (p < 0.001) or location (p < 0.001). CONCLUSIONS: Large vessel area, plaque burden, proximal location, right coronary artery location, and lack of calcium were associated with FA plaque rupture. The present study suggests that among these variables, vessel area may be the strongest predictor of plaque rupture among non-left main coronary arteries. ( PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions [PROSPECT]; NCT00180466).

Usefulness of Coronary Atheroma Burden to Predict Cardiovascular Events in Patients Presenting With Acute Coronary Syndromes (from the PROSPECT Study).

We investigated the relation between overall atheroma burden and clinical events in the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study. In PROSPECT, 660 patients (3,229 nonculprit lesions with a plaque burden ≥ 40% and complete intravascular ultrasound data) were divided into tertiles according to baseline percent atheroma volume (PAV: total plaque/vessel volume). Patients were followed for 3.4 years (median); major adverse cardiac events (MACE: death from cardiac causes, cardiac arrest, myocardial infarction, or rehospitalization because of unstable or progressive angina) were adjudicated to either culprit or nonculprit lesions. Compared with patients in low or intermediate PAV tertiles, patients in the high PAV tertile had the greatest prevalence of plaque rupture and radiofrequency thin-cap fibroatheroma (VH-TCFA) and the highest percentage of necrotic core volume; they were also more likely to have high-risk lesion characteristics: ≥ 1 lesion with minimal luminal area ≤ 4 mm(2), plaque burden >70%, and/or VH-TCFA. Three-year cumulative nonculprit lesion-related MACE was greater in the intermediate and high tertiles than in the low tertile (6.3% vs 14.7% vs 15.1%, low vs intermediate vs high tertiles, p = 0.009). On Cox multivariable analysis, insulin-dependent diabetes (hazard ratio [HR] 3.98, p = 0.002), PAV (HR 1.06, p = 0.03), and the presence of ≥1 VH-TCFA (HR 1.80, p = 0.02) were independent predictors of nonculprit MACE. In conclusion, increasing baseline overall atheroma burden was associated with more advanced, complex, and vulnerable intravascular ultrasound lesion morphology and independently predicted nonculprit lesion-related MACE in patients with acute coronary syndromes after successful culprit lesion intervention.

Impact of positive and negative lesion site remodeling on clinical outcomes: insights from PROSPECT.

OBJECTIVES: This study investigated coronary artery remodeling patterns associated with clinical outcomes. BACKGROUND: In the prospective, multicenter PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree: An Imaging Study in Patients With Unstable Atherosclerotic Lesions) study, reported predictors of nonculprit lesion (NCL) major adverse cardiac events (MACE) were an intravascular ultrasound (IVUS) minimal lumen area (MLA) ≤4 mm(2), a plaque burden ≥70%, and a IVUS-virtual histology (VH) thin-cap fibroatheroma (TCFA), but not lesion site remodeling. METHODS: Overall, 697 consecutive patients with an acute coronary syndrome were enrolled and underwent 3-vessel gray-scale and IVUS-VH; 3,223 NCLs were identified by IVUS. The remodeling index (RI) was calculated as the external elastic membrane area at the MLA site divided by the average of the proximal and distal reference external elastic membrane areas. First, one third of the patients were randomly selected to determine RI cutoffs related to NCL MACE (development cohort). Receiver-operating characteristic analysis showed that there were 2 separate cut points that predicted NCL MACE: RI = 0.8789 and RI = 1.0046 (area under the curve = 0.663). These cut points were used to define negative remodeling as an RI <0.88, intermediate remodeling as an RI of 0.88 to 1.00, and positive remodeling as an RI >1.00. Second, we used the remaining two-thirds of patients to validate these cut points with respect to lesion morphology and clinical outcomes (validation cohort). RESULTS: Kaplan-Meier curve analysis in the validation cohort showed that NCL MACE occurred more frequent (and equally) in negative and positive remodeling lesions compared with intermediate remodeling lesions. In this cohort, negative remodeling lesions had the smallest MLA, positive remodeling lesions had the largest plaque burden, and VH TCFA, especially VH TCFA with multiple necrotic cores, was most common in negatively remodeling lesions. CONCLUSIONS: The present study showed the novel concept that positive and negative lesion site remodeling was associated with unanticipated NCL MACE in the PROSPECT study. ( PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions [PROSPECT]; NCT00180466).

Non-fibroatheroma lesion phenotype and long-term clinical outcomes: a substudy analysis from the PROSPECT study.

OBJECTIVES: The purpose of this study was to determine the clinical impact of non-fibroatheroma lesion phenotype in patients presenting with an acute coronary syndrome (ACS). BACKGROUND: Although fibroatheromas (FAs) are known to be clinically unstable, the impact of non-FA lesion phenotype on clinical outcomes has not been studied. METHODS: In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, patients presenting with an ACS underwent 3-vessel grayscale and virtual histology intravascular ultrasound (VH-IVUS) after successful percutaneous intervention for all culprit lesions and were followed for 3 years. Patients were divided into those who had only the non-FA phenotype (pathological intimal thickening or fibrotic and/or fibrocalcific lesions) versus those who had at least 1 nonculprit FA. RESULTS: Among 2,880 nonculprit lesions identified by VH-IVUS, 39.8% were non-FAs (1,042 pathological intimal thickening, 72 fibrotic, and 33 fibrocalcific). Nonculprit major adverse cardiac events (MACE) (death, myocardial infarction, or urgent rehospitalization for progressive or unstable angina) were attributed to only 7 non-FA lesions (0.7%) versus 43 FA lesions (2.7%, p < 0.001) during 3 years follow-up. Of 609 patients, 67 (11.0%) patients had only non-FA lesion phenotypes. Patients with only non-FAs tended to be younger and more often female, have fewer nonculprit lesions and less overall plaque burden and necrotic core, and fewer nonculprit lesion MACE compared with patients with at least 1 FA. In the adjusted Cox proportional hazards model, absence of a FA was a significant predictive of a lower 3-year nonculprit MACE rate (hazard ratio: 0.23; 95% confidence interval: 0.06 to 0.95). CONCLUSIONS: Non-FA lesions were clinically stable and were rarely associated with clinical events during 3 years of follow-up. The intermediate-term prognosis in patients presenting with ACS in whom all nonculprit lesions are non-FAs is favorable. ( PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466).

Gender and the extent of coronary atherosclerosis, plaque composition, and clinical outcomes in acute coronary syndromes.

OBJECTIVES: This study sought to assess the extent and composition of atherosclerosis contributing to acute coronary syndrome events in women compared with men. BACKGROUND: Pathological studies suggest that plaque composition and burden may differ by sex. It is unclear whether sex impacts the extent, characteristics, and potential vulnerability of coronary plaques. METHODS: A total of 697 patients (24% women) with acute coronary syndromes were enrolled in the prospective, multicenter PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. Three-vessel multimodality intracoronary imaging (quantitative coronary angiography, grayscale, and radiofrequency intravascular ultrasound [IVUS]) was performed after treatment of the culprit lesion(s). Events during a median 3.4-year follow-up were ascribed to recurrent culprit versus untreated nonculprit lesions. The authors performed a post hoc, sex-based subgroup analysis. RESULTS: Women were older and had more comorbid disease than men. By angiography, women had a similar number of angiographic culprit (p = 0.53) but fewer nonculprit (p = 0.05) lesions, and fewer vessels with nonculprit lesions (p = 0.048) compared with men even after multivariable adjustment (p = 0.002). By IVUS, women had fewer nonculprit lesions (p = 0.002), but similar plaque burden (PB) per lesion (55.6% vs. 55.3%; p = 0.35), and female sex was not predictive of severe (> 70%) PB (p = 0.052). Plaque rupture was less common in women (6.6% vs. 16.3%; p = 0.002) even after adjusting for comorbidities (p = 0.004), as was the total necrotic core volume (p < 0.0001). The frequency of other plaque phenotypes was similar for men and women including pathological intimal thickening, thin-cap fibroatheromas (TCFA), and thick-cap fibroatheromas. Rates of major adverse cardiovascular events attributed to culprit and nonculprit lesions at 1-, 2-, and 3-year follow-up were not significantly different between men and women, although women were rehospitalized more frequently due to culprit lesion-related angina. For men, nonculprit lesion minimal lumen area ≤ 4.0 mm(2), PB ≥70%, and TCFA predicted nonculprit MACE at 3 years, whereas for women, only TCFA and PB were predictive. CONCLUSIONS: The PROSPECT study validates that despite having more comorbid risk factors than men, women have less extensive coronary artery disease by both angiographic and IVUS measures, and that lesions in women compared with men have less plaque rupture, less necrotic core and calcium, similar plaque burden, and smaller lumens. TCFA may also be a stronger marker of plaque vulnerability in women than men.

Relation between angiographic lesion severity, vulnerable plaque morphology and future adverse cardiac events (from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree study).

Previous angiographic studies have suggested that the future risk for major adverse cardiovascular events (MACEs) is related to coronary stenosis severity. The aim of this study was to use the grayscale and virtual histology (VH)-intravascular ultrasound (IVUS) data from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study to identify underlying lesion morphologic characteristics that might explain these findings. In PROSPECT, patients presenting with acute coronary syndromes in whom percutaneous coronary intervention was successful underwent 3-vessel grayscale and VH-IVUS and were followed for a median of 3.4 years for the incidence of MACEs. Overall, 3,115 nonculprit lesions detected by IVUS were divided into quartiles according to baseline angiographic diameter stenosis. From the first to fourth quartiles, there were increases in the prevalence of lesions with IVUS minimum luminal areas ≤ 4 mm(2), IVUS plaque burden ≥ 70%, and VH-IVUS thin-cap fibroatheroma (13.4%, 22.0%, 24.2%, and 30.3%, respectively, p <0.001), along with an increased frequency of plaque ruptures and greater necrotic core volumes. The incidence of lesions with plaque burden ≥ 70%, minimum luminal area ≤ 4 mm(2), and VH thin-cap fibroatheroma was highest in the fourth quartile (0%, 0.4%, 0.4%, and 2.8% in the first through fourth quartiles, respectively, p <0.001). Three-year MACE rates were also highest in the fourth quartile (0.3%, 0.7%, 1.3%, and 5.1%, respectively, p <0.001). In conclusion, increasing angiographic diameter stenosis was associated with an increased frequency of grayscale and VH-IVUS lesion morphologic features that have been associated with adverse events and that may, in part, explain why future MACEs were related to baseline lesion severity.

Characteristics and clinical significance of angiographically mild lesions in acute coronary syndromes.

OBJECTIVES: The aim of this study was to assess whether residual nonculprit (NC) lesions, defined as visual diameter stenosis ≥ 30% after successful percutaneous coronary intervention, affect the rate of future events in patients with acute coronary syndromes. BACKGROUND: In patients with acute coronary syndromes, approximately one-half of recurrent events after percutaneous coronary intervention arise from untreated lesions. METHODS: Patients enrolled in PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) were divided into 3 groups: those with no NC lesions, 1 NC lesion, or ≥ 2 NC lesions. Time to events for major adverse cardiac events was estimated up to 3 years. RESULTS: Among 697 patients, 13.3% had no NC lesions, 19.7% had 1 NC lesion, and 67.0% had ≥ 2 NC lesions. The median diameter stenoses of the NC lesions in the latter 2 groups were 36.7% (interquartile range: 31.0% to 43.4%) and 37.4% (interquartile range: 32.0% to 46.5%), respectively (p = 0.22). At least 1 thin-cap fibroatheroma was present in one-half the patients in each group. At 3 years, the incidence of major adverse cardiac events was 8.5%, 15.2%, and 24.3%, respectively (p = 0.0009). NC lesion-related events occurred in 0%, 5.0%, and 15.9% of patients, respectively (p < 0.0001). Of 105 NC lesion-related clinical events occurring during follow-up, 73 (69.5%) originated from angiographically evident baseline NC lesions (of which 36 had diameter stenosis >50%), while the other 32 arose from normal or near normal segments. CONCLUSIONS: Residual NC lesions are common after percutaneous coronary intervention for acute coronary syndromes and portend a higher rate of recurrent ischemic events within 3 years, especially when angiographically more severe. Conversely, the absence of NC lesions by angiography is highly predictive of freedom from events not related to the originally treated culprit lesion(s).

Three-year results of safety and efficacy of the everolimus-eluting coronary stent in women (from the SPIRIT III randomized clinical trial).

Women treated with the XIENCE V have improved 1-year clinical outcomes compared to women treated with TAXUS; whether benefits in women are sustained at 3 years is unknown. Three-year follow-up of the SPIRIT III trial revealed improved clinical outcomes of the XIENCE V everolimus-eluting stent compared to the TAXUS paclitaxel-eluting stent. One thousand two patients with coronary artery lesions ≤28 mm in length in 2.5- to 3.75-mm diameter vessels were prospectively randomized to receive XIENCE V or TAXUS stents. A post hoc gender subset analysis was performed. Six hundred sixty-nine patients (30% women) received XIENCE V and 332 patients (34% women) received TAXUS. In the overall population, women had higher 3-year rates of major adverse cardiac events (16.0% vs 10.0%, p = 0.01) and target lesion revascularization (10.2% vs 5.3%, p = 0.008) compared to men. In women, those with XIENCE V continued to have lower major adverse cardiac event rates than those with TAXUS at 2 years (9.5% vs 18.3%, p = 0.03) and 3 years (12.2% vs 22.6%, p = 0.03). Although 1-year target vessel failure rates were similar, at 2- and 3-year follow-up women treated with XIENCE V had approximately 40% relative decreases in target vessel failure rates compared to those treated with TAXUS (12.7% vs 22.0%, p = 0.05; 16.0% vs 26.4%, p = 0.03, respectively). Stent thrombosis and bleeding complication rates were similar between treatment arms in the gender subgroups through 3 years. In conclusion, women in the SPIRIT III trial have sustained clinical benefits from XIENCE V implantation compared to TAXUS without increases in long-term complications.

Long-term (three-year) safety and efficacy of everolimus-eluting stents compared to paclitaxel-eluting stents (from the SPIRIT III Trial).

The safety and efficacy of the XIENCE V everolimus-eluting stent (EES) compared to the Taxus Express(2) paclitaxel-eluting stent (PES) has been demonstrated through 2 years in the SPIRIT II and III randomized clinical trials, but limited longer-term data have been reported. In the SPIRIT III trial, 1,002 patients with up to 2 lesions in 2 coronary arteries were randomized 2:1 to EESs versus PESs at 65 United States sites. At completion of 3-year follow-up, treatment with EES compared to PES resulted in a significant 30% decrease in the primary clinical end point of target vessel failure (cardiac death, myocardial infarction, or ischemic-driven target vessel revascularization, 13.5% vs 19.2%, hazard ratio 0.70, 95% confidence interval 0.50 to 0.96, p = 0.03) and a 43% decrease in major adverse cardiovascular events, cardiac death, myocardial infarction, or ischemic-driven target lesion revascularization (9.1% vs 15.7%, hazard ratio 0.57, 95% confidence interval 0.39 to 0.83, p = 0.003). In a landmark analysis, major adverse cardiovascular events were decreased to a similar extent with EES compared to PES 0 through 1 year and 1 year through 3 years (hazard ratio 0.56, 95% confidence interval 0.35 to 0.90; hazard ratio 0.59, 95% confidence interval 0.31 to 1.11, respectively). In conclusion, patients treated with EES rather than PES in the SPIRIT III trial had significantly improved event-free survival at 3 years. From 1 year to 3 years hazard curves continued to diverge in favor of EES, consistent with an improving long-term safety and efficacy profile of EES compared to PES, with no evidence of late catchup.

Outcomes in diabetic and nondiabetic patients treated with everolimus- or paclitaxel-eluting stents: results from the SPIRIT IV clinical trial (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System).

OBJECTIVES: We compared the safety and efficacy of the XIENCE V (Abbott Vascular, Santa Clara, California) everolimus-eluting stent (EES) with the TAXUS Express (Boston Scientific, Natick, Massachusetts) paclitaxel-eluting stent (PES) among the large cohort of randomized diabetic patients enrolled in the SPIRIT IV (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) trial. BACKGROUND: Diabetes mellitus remains a significant predictor of adverse clinical outcomes after percutaneous coronary intervention with drug-eluting stents, and the comparative outcomes of different drug-eluting stents in diabetic patients remains ill-defined. METHODS: In the SPIRIT IV trial, 3,687 patients with up to 3 de novo native coronary artery lesions were prospectively randomized 2:1 to receive EES or PES. Randomization was stratified by the presence of diabetes and lesion complexity. The primary end point was the occurrence of target lesion failure (TLF) (cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization) at 1 year. Clinical outcomes were evaluated in randomized diabetic (n = 1,185 [786 EES; 399 PES]) and nondiabetic patients (n = 2,498 [1,669 EES; 829 PES]). RESULTS: The EES compared with PES reduced TLF in nondiabetic patients (3.1% vs. 6.7%, p < 0.0001), with significant reductions in myocardial infarction, stent thrombosis, and target lesion revascularization. In contrast, no difference in TLF (6.4% vs. 6.9%, respectively, p = 0.80) or any of its components was present among diabetic patients, regardless of insulin use. A significant interaction between the presence of diabetes and stent type on TLF (p(interaction) = 0.02) was observed. CONCLUSIONS: In the SPIRIT IV randomized trial, EES compared with PES provided similar clinical outcomes in diabetic patients and superior clinical outcomes in nondiabetic patients at 1 year. (SPIRIT IV Clinical Trial: Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions; NCT00307047).

Side branch occlusion with everolimus-eluting and paclitaxel-eluting stents: three-year results from the SPIRIT III randomised trial.

AIMS AND METHODS: The rates of side branch occlusion and subsequent periprocedural MI during everolimus-eluting stent (EES) and paclitaxel-eluting stent (PES) placement were examined in the randomised SPIRIT III trial. Periprocedural myocardial infarction (MI) following drug-eluting stent placement is associated with long-term adverse outcomes. Occlusion of side branches may be an important factor contributing to periprocedural MIs. Consecutive procedural angiograms of patients randomly assigned to EES (n=669) or PES (n=333) were analysed by an independent angiographic core laboratory. Side branch occlusion was defined as Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 or 1. Clinical outcomes through three years were compared by stent type and presence of side branch occlusion. CONCLUSIONS: A total of 2,048 side branches were evaluated (EES N=1,345 side branches in 688 stented lesions, PES N=703 side branches in 346 stented lesions). Patients with compared to those without transient or final side branch occlusion had significantly higher non-Q-wave MI (NQMI) rates in-hospital (9.0% vs. 0.5%, p<0.0001). By multivariable analysis side branch occlusion was an independent predictor of NQMI (OR 4.45; 95% CI [1.82, 10.85]). Transient or final side branch occlusion occurred less frequently in patients receiving EES compared to PES (2.8% vs. 5.2%, p=0.009), contributing to the numerically lower rates of in-hospital NQMI with EES arm compared to PES (0.7% vs. 2.3%, p=0.05). Patients treated with EES rather than PES were less likely to develop side branch occlusion during stent placement, contributing to lower rates of periprocedural MI with EES compared to PES.

Clinical evaluation of the Zilver vascular stent for symptomatic iliac artery disease.

PURPOSE: To evaluate the safety and effectiveness of the Zilver vascular stent in the treatment of de novo or restenotic lesions in the external and common iliac arteries. MATERIALS AND METHODS: Regardless of the results of an initial percutaneous transluminal angioplasty (PTA), 151 consecutive patients were implanted with Zilver vascular stents (Cook, Bloomington, Ind) in up to two stenotic (< or =10 cm) or occluded (< or =5 cm) atherosclerotic lesions of the external or common iliac arteries. The primary endpoint was the rate of major adverse events within 9 months after the procedure. Major adverse events were defined as death, myocardial infarction, target lesion revascularization, and limb loss. Secondary endpoints included acute procedural success, 30-day clinical success, 9-month patency rate, 9-month functional status (on the basis of the validated Walking Impairment Questionnaire), and ankle-brachial index (ABI). RESULTS: of 1-, 6-, and 9-month follow-up are reported. Results The 9-month device and/or procedural-related major adverse event rate (adjudicated by an independent clinical events committee) was 2.7%. The all-cause major adverse event rate was 7.5%. Both rates were substantially below the prespecified objective performance criterion of 16%. The acute procedure success rate and 30-day clinical success rate were 98.0% and 94.0%, respectively. The 9-month patency rate, measured with duplex ultrasonography, was 92.9%. Significant improvement in the ABI and walking distance and walking speed scores, relative to preprocedural values, was seen at 1 month and was maintained through 9-month follow-up. CONCLUSIONS: The Zilver vascular stent is safe and effective as an adjunct to PTA in the treatment of symptomatic disease of the iliac arteries.

A novel filter-based distal embolic protection device for percutaneous intervention of saphenous vein graft lesions: results of the AMEthyst randomized controlled trial.

OBJECTIVES: We sought to evaluate the relative safety and efficacy of the novel Interceptor PLUS Coronary Filter System (Medtronic Vascular, Santa Rosa, California) compared with approved embolic-protection devices (e.g., GuardWire, Medtronic Vascular/FilterWire EZ, Boston Scientific, Natick, Massachusetts) during percutaneous coronary intervention (PCI) of degenerative saphenous vein grafts (SVG). BACKGROUND: Percutaneous coronary intervention of degenerative SVG is associated with embolization of atherothrombotic debris and subsequent myocardial infarction in a significant portion of patients. The use of distal embolic-protection devices has previously been demonstrated to reduce major adverse cardiovascular events associated with PCI in these patients. METHODS: In this multicenter, randomized noninferiority trial, 797 patients undergoing PCI with stenting of SVG stenoses (de novo or restenotic) with reference vessel diameter 2.5 mm to 5.25 mm were randomly assigned 2:1 to either the Interceptor PLUS (n = 533) or control distal-protection devices (GuardWire [n = 191], FilterWire EZ [n = 73]) at the physician's discretion. RESULTS: The trial primary clinical end point (composite occurrence of death, myocardial infarction, or urgent repeat revascularization through 30 days) was observed in 8% and 7.3% of Interceptor and control-treated patients, respectively (p = 0.025 for noninferiority; p = 0.77 for difference). Key secondary end points for device and procedural success were similar between randomly assigned treatment strategies. CONCLUSIONS: The Interceptor PLUS Coronary Filter System is noninferior in safety and efficacy to 30 days when compared with the GuardWire and FilterWire EZ distal embolic protection devices.