Coronary Artery Disease: Ellis SG

King SB, Aversano T, Ballard WL, Beekman RH, Cowley MJ, Ellis SG, Faxon DP, Hannan EL, Hirshfeld JW, Jacobs AK, Kellett MA, Kimmel SE, Landzberg JS, McKeever LS, Moscucci M, Pomerantz RM, Smith KM, Vetrovec GW, Creager MA, Hirshfeld JW, Holmes DR, Newby LK, Weitz HH, Merli G, Piña I, Rodgers GP, Tracy CM, Anonymous00143, Anonymous00144, Anonymous00145. · No affiliation provided · J Am Coll Cardiol. · Pubmed #17601554 No free full text.

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Anonymous00180, King SB, Aversano T, Ballard WL, Beekman RH, Cowley MJ, Ellis SG, Faxon DP, Hannan EL, Hirshfeld JW, Jacobs AK, Kellett MA, Kimmel SE, Landzberg JS, McKeever LS, Moscucci M, Pomerantz RM, Smith KM, Vetrovec GW, Creager MA, Holmes DR, Newby LK, Weitz HH, Merli G, Piña I, Rodgers GP, Tracy CM. · No affiliation provided · Circulation. · Pubmed #17592076 links to  free full text

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Ellis SG. · No affiliation provided · N Engl J Med. · Pubmed #19144945 No free full text.

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Barman N, Chiu JH, Ellis SG. · The Cleveland Clinic Foundation, Department of Cardiovascular Medicine, Cleveland, OH, USA. · J Invasive Cardiol. · Pubmed #15550734 No free full text.

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Schoenhagen P, Tuzcu EM, Ellis SG. · No affiliation provided · Circulation. · Pubmed #12176939 links to  free full text

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Khot UN, Friedman DT, Pettersson G, Smedira NG, Li J, Ellis SG. · Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio, USA. · Circulation. · Pubmed #15123539 links to  free full text

Abstract: BACKGROUND: The radial artery has been increasingly used in CABG. However, angiographic outcome data have been limited. METHODS AND RESULTS: We reviewed all coronary angiography procedures from February 1996 to October 2001 and selected patients with a radial artery bypass graft. Angiographic outcomes were divided into groups as (1) occluded, (2) severe disease (> or =70% stenosis, or string sign), or (3) patent (<70% stenosis). Multivariable analyses determined predictors of severe disease or occlusion. A total of 310 patients had a radial artery graft. Mean follow-up after coronary artery bypass grafting was 565+/-511 days. Radial artery grafts had a patency rate of 51.3%, which was significantly lower than that for left internal mammary arteries (90.3%, P<0.0001) or saphenous vein grafts (64.0%, P=0.0016). Radial artery grafts had an occlusion rate of 33.7%, compared with 4.8% for left internal mammary arteries (P<0.0001), and had a severe stenosis rate of 15.1%, compared with 5.9% for saphenous vein grafts (P=0.0003) and 4.8% for left internal mammary arteries (P<0.0001). Women had a worse overall radial artery patency rate than men (38.9% versus 56.1%, P=0.025). A radial artery graft was the most powerful multivariable predictor of severe stenosis or occlusion (chi2=28.87, P<0.0001). Because of diseased radial artery grafts, 58 patients required subsequent percutaneous intervention, and 26 patients required repeat CABG. CONCLUSIONS: In patients predominantly presenting with signs and symptoms of myocardial ischemia after CABG, radial artery grafts have lower patency rates than left internal mammary artery and saphenous vein grafts. Selective use of the radial artery is warranted, particularly in women.

Shishehbor MH, Lauer MS, Singh IM, Chew DP, Karha J, Brener SJ, Moliterno DJ, Ellis SG, Topol EJ, Bhatt DL. · Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA. · J Am Coll Cardiol. · Pubmed #17320742 No free full text.

Abstract: OBJECTIVES: We examined the safety and efficacy of nonculprit multivessel compared with culprit-only stenting in patients with multivessel disease presenting with unstable angina or non-ST-segment elevation myocardial infarction (non-ST-segment elevation acute coronary syndromes [NSTE-ACS]). BACKGROUND: In patients presenting with NSTE-ACS, multivessel coronary artery disease (CAD) is associated with adverse outcome. METHODS: Patients with multivessel CAD and NSTE-ACS that underwent percutaneous coronary intervention were included. The culprit lesion was defined by reviewing each patient's angiographic report, electrocardiogram, echocardiogram and, if available, nuclear stress test. All patients had at least 2 vessels with > or =50% stenosis, and the angiographic severity of CAD was assessed using the Duke Prognostic Angiographic Score. Patients with coronary bypass grafts, chronic total occlusions, and those with uncertain culprit lesions were excluded. Our end point was the composite of death, myocardial infarction, or any target vessel revascularization. RESULTS: From January 1995 to June 2005, 1,240 patients with ACS and multivessel CAD underwent percutaneous coronary intervention with bare-metal stenting and met our study criteria. Of these, 479 underwent multivessel and 761 underwent culprit-only stenting. There were 442 events during a median follow-up of 2.3 years. Multivessel intervention was associated with lower death, myocardial infarction, or revascularization after both adjusting for baseline and angiographic characteristics (hazard ratio 0.80; 95% confidence interval 0.64 to 0.99; p = 0.04) and propensity matched analysis (hazard ratio 0.67; 95% confidence interval 0.51 to 0.88; p = 0.004). CONCLUSIONS: In patients with multivessel CAD presenting with NSTE-ACS, multivessel intervention was significantly associated with a lower revascularization rate, which translated to a lower incidence of the composite end point compared with culprit-only stenting.

Stone GW, Ellis SG, Cannon L, Mann JT, Greenberg JD, Spriggs D, O'Shaughnessy CD, DeMaio S, Hall P, Popma JJ, Koglin J, Russell ME, Anonymous00122. · Department of Cardiology, Columbia University Medical Center and Cardiovascular Research Foundation, New York, NY 10032, USA. · JAMA. · Pubmed #16160130 No free full text.

Abstract: CONTEXT: Compared with bare metal stents, drug-eluting stents reduce restenosis in noncomplex lesions. The utility of drug-eluting stents has not been evaluated in more difficult stenoses. OBJECTIVE: To investigate the safety and efficacy of the polymer-based, slow-release paclitaxel-eluting stent in a patient population with more complex lesions than previously studied. DESIGN, SETTING, AND PATIENTS: Prospective, placebo-controlled, double-blind, multicenter randomized trial conducted from February 2003 to March 2004 at 66 academic and community-based institutions with 1156 patients who underwent stent implantation in a single coronary artery stenosis (vessel diameter, 2.25-4.0 mm; lesion length, 10-46 mm), including 664 patients (57.4%) with complex or previously unstudied lesions (requiring 2.25-mm, 4.0-mm, and/or multiple stents) and 9-month clinical and angiographic follow-up. INTERVENTIONS: Patients were randomly assigned to receive 1 or more bare metal stents (n = 579) or identical-appearing paclitaxel-eluting stents (n = 577). MAIN OUTCOME MEASURE: Ischemia-driven target vessel revascularization at 9 months. RESULTS: Baseline characteristics were well matched. Diabetes was present in 31% of patients. The mean (SD) reference vessel diameter was 2.69 (0.57) mm, the reference lesion length was 17.2 (9.2) mm, and 78% of lesions were type B2/C. A mean (SD) of 1.38 (0.58) stents (total mean [SD] length, 28.4 [13.1] mm) were implanted per lesion; 33% of lesions required multiple stents. Stents that were 2.25 mm and 4.0 mm in diameter were used in 18% and 17% of lesions, respectively. Compared with bare metal stents, paclitaxel-eluting stents reduced the 9-month rate of target lesion revascularization from 15.7% to 8.6% (P<.001) and target vessel revascularization from 17.3% to 12.1% (P = .02). Similar rates were observed for cardiac death or myocardial infarction (5.5% for bare metal stent group vs 5.7% for paclitaxel-eluting stent group) and stent thrombosis (0.7% in both groups). Angiographic restenosis was reduced from 33.9% to 18.9% in the entire study cohort (P<.001), including among patients receiving 2.25-mm stents (49.4% vs 31.2%; P = .01), 4.0-mm stents (14.4% vs 3.5%; P = .02), and multiple stents (57.8% vs 27.2%; P<.001). CONCLUSION: Compared with a bare metal stent, implantation of the paclitaxel-eluting stent in a patient population with complex lesions effectively reduces clinical and angiographic restenosis.

Lansky AJ, Costa RA, Mooney M, Midei MG, Lui HK, Strickland W, Mehran R, Leon MB, Russell ME, Ellis SG, Stone GW, Anonymous00035. · Columbia University Medical Center and Cardiovascular Research Foundation, New York, New York, USA. · J Am Coll Cardiol. · Pubmed #15837246 No free full text.

Abstract: OBJECTIVES: We sought to determine whether gender influences the results of paclitaxel-eluting stent implantation. BACKGROUND: The TAXUS-IV trial demonstrated the safety and effectiveness of the slow-release, polymer-based, paclitaxel-eluting TAXUS stent compared to bare-metal stents in patients undergoing elective coronary intervention. Whether these results are generalizable to women is not known. METHODS: A total of 1,314 patients with coronary lesions 10- to 28-mm long in 2.5- to 3.75-mm vessels were randomized to TAXUS stent versus bare-metal EXPRESS stents (Boston Scientific Corp., Natick, Massachusetts). Outcomes examined were stratified by gender. RESULTS: A total of 662 patients (including 187 women) were assigned to the TAXUS stent, and 652 (180 women) received the control stent. Women were older than men, and had more hypertension, diabetes, renal insufficiency, unstable angina, and heart failure, but less smoking. Among patients receiving the TAXUS stent, women compared with men had higher unadjusted one-year rates of target lesion revascularization (TLR) (7.6% vs. 3.2%, p = 0.03), though female gender was not an independent predictor of TLR (odds ratio [OR] = 1.72 [95% confidence interval (CI) 0.68 to 4.37], p = 0.25). Moreover, restenosis rates were similar in men and women treated with the TAXUS stent (8.6% vs. 7.6%, respectively, p = 0.80), as was late loss (0.22 vs. 0.23 mm, p = 0.90). Compared to control stents, treatment with the TAXUS stent in women resulted in a significant reduction in nine-month restenosis (8.6% vs. 29.2%, p = 0.0001) and one-year TLR (7.6% vs. 14.9%, p = 0.02). The only independent predictor of freedom from restenosis in women was randomization to the TAXUS stent (OR = 0.28 [95% CI 0.11 to 0.74], p = 0.01). CONCLUSIONS: The benefits of the paclitaxel-eluting stent in reducing clinical and angiographic restenosis are generalizable to women.

Stone GW, Ellis SG, Cox DA, Hermiller J, O'Shaughnessy C, Mann JT, Turco M, Caputo R, Bergin P, Greenberg J, Popma JJ, Russell ME, Anonymous00119. · Cardiovascular Research Foundation and Lenox Hill Heart and Vascular Institute, New York 10022, USA. · N Engl J Med. · Pubmed #14724301 links to  free full text

Abstract: BACKGROUND: Restenosis after coronary stenting necessitates repeated percutaneous or surgical revascularization procedures. The delivery of paclitaxel to the site of vascular injury may reduce the incidence of neointimal hyperplasia and restenosis. METHODS: At 73 U.S. centers, we enrolled 1314 patients who were receiving a stent in a single, previously untreated coronary-artery stenosis (vessel diameter, 2.5 to 3.75 mm; lesion length, 10 to 28 mm) in a prospective, randomized, double-blind study. A total of 652 patients were randomly assigned to receive a bare-metal stent, and 662 to receive an identical-appearing, slow-release, polymer-based, paclitaxel-eluting stent. Angiographic follow-up was prespecified at nine months in 732 patients. RESULTS: In terms of base-line characteristics, the two groups were well matched. Diabetes mellitus was present in 24.2 percent of patients; the mean reference-vessel diameter was 2.75 mm, and the mean lesion length was 13.4 mm. A mean of 1.08 stents (length, 21.8 mm) were implanted per patient. The rate of ischemia-driven target-vessel revascularization at nine months was reduced from 12.0 percent with the implantation of a bare-metal stent to 4.7 percent with the implantation of a paclitaxel-eluting stent (relative risk, 0.39; 95 percent confidence interval, 0.26 to 0.59; P<0.001). Target-lesion revascularization was required in 3.0 percent of the group that received a paclitaxel-eluting stent, as compared with 11.3 percent of the group that received a bare-metal stent (relative risk, 0.27; 95 percent confidence interval, 0.16 to 0.43; P<0.001). The rate of angiographic restenosis was reduced from 26.6 percent to 7.9 percent with the paclitaxel-eluting stent (relative risk, 0.30; 95 percent confidence interval, 0.19 to 0.46; P<0.001). The nine-month composite rates of death from cardiac causes or myocardial infarction (4.7 percent and 4.3 percent, respectively) and stent thrombosis (0.6 percent and 0.8 percent, respectively) were similar in the group that received a paclitaxel-eluting stent and the group that received a bare-metal stent. CONCLUSIONS: As compared with bare-metal stents, the slow-release, polymer-based, paclitaxel-eluting stent is safe and markedly reduces the rates of clinical and angiographic restenosis at nine months.

Eppler SM, Combs DL, Henry TD, Lopez JJ, Ellis SG, Yi JH, Annex BH, McCluskey ER, Zioncheck TF. · Clinical and Experimental Pharmacology Department, the Bioanalytical Assays Department, and the Medical Affairs Department, Genentech, South San Francisco, CA 94080, USA. · Clin Pharmacol Ther. · Pubmed #12152001 No free full text.

Abstract: BACKGROUND: The Vascular Endothelial Growth Factor (VEGF) in Ischemia for Vascular Angiogenesis (VIVA) trial was a double-blind, placebo-controlled, phase II clinical trial designed to evaluate the safety, efficacy, and pharmacokinetics of combined intracoronary and intravenous infusions of recombinant human vascular endothelial growth factor (rhVEGF(165)) for therapeutic angiogenesis. This study describes the use of a mechanism-based model to characterize the nonlinear kinetics observed after intravenous administration of rhVEGF(165). The model predicts that rhVEGF(165) distribution occurs through both saturable binding to high-affinity receptors and reversible interactions with low-affinity binding sites. METHODS: In this trial, rhVEGF(165) was administered to patients with coronary artery disease at a dose rate of 17 or 50 ng/kg/min by means of intracoronary infusion for 20 minutes, followed by three 4-hour intravenous infusions on days 3, 6, and 9. Pharmacokinetic samples and blood pressure measurements were collected at baseline, during infusion, and for 6 hours after infusion. RESULTS: The plasma clearance, steady-state volume of distribution, and terminal half-life after a 4-hour intravenous infusion of rhVEGF(165) at the high dose were 19.1 +/- 5.7 mL/min/kg, 960 +/- 260 mL/kg, and 33.7 +/- 13 minutes, respectively. The duration of hypotension that occurred after rhVEGF(165) administration appeared to be related to the model-predicted VEGF(165) concentration associated with the high-affinity receptor compartment. CONCLUSIONS: This mechanism-based model accurately predicted VEGF concentrations and allowed for the simulation of various rhVEGF(165) dose regimens that may aid in optimization of drug delivery for future clinical trials.

Cura FA, Bhatt DL, Lincoff AM, Kapadia SR, L'Allier PL, Ziada KM, Wolski KE, Moliterno DJ, Brener SJ, Ellis SG, Topol EJ. · Department of Cardiology, The Cleveland Clinic Foundation, OH 44195, USA. · Circulation. · Pubmed #10880411 links to  free full text

Abstract: BACKGROUND: Previous trials testing stents compared with balloon angioplasty excluded patients with complex lesions and did not assess the effect of adjunctive platelet IIb/IIIa inhibition. This analysis sought to assess the effect of stenting and abciximab specifically for patients with complex lesions. METHODS AND RESULTS: Patients with complex lesions (long, tandem, severely calcified, restenotic, thrombotic, or ostial; total occlusions; bifurcations; saphenous vein grafts; and multivessel interventions) from the Evaluation of PTCA to Improve Long-Term Outcome by c7E3 GP IIb/IIIa Receptor Blockade (EPILOG) and the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trials were included in the analysis. The 1-year combined death or myocardial infarction rates in the 4 treatment groups were as follows: balloon angioplasty/placebo, 14.2%; stent/placebo, 15.8%; balloon angioplasty/abciximab, 7.6%; and stent/abciximab, 8.0% (P<0.001). Death rates were 3.2%, 3.1%, 2.1%, and 0.5%, respectively (P=0.03). The incidence of target vessel revascularization at 1 year was 30.5%, 18.0%, 24.4%, and 19.7% in the 4 groups, respectively (P<0.001). After adjustment for baseline differences, multivariate analysis demonstrated that the rate of death or myocardial infarction was independently reduced by balloon angioplasty/abciximab (hazard ratio, 0.51; P<0.001) and stent/abciximab (hazard ratio, 0.60; P=0.02) but was not affected by the use of stents alone. Conversely, target vessel revascularization was reduced by stent/placebo (hazard ratio, 0.53; P<0.001), stent/abciximab (hazard ratio, 0.58; P<0.001), and balloon angioplasty/abciximab (hazard ratio, 0.74; P=0.006) compared with balloon angioplasty/placebo, respectively. CONCLUSIONS: The combination of stenting and abciximab during percutaneous coronary interventions for patients with angiographically complex lesions confers additive long-term benefit with respect to death, myocardial infarction, and target vessel revascularization.

Marso SP, Lincoff AM, Ellis SG, Bhatt DL, Tanguay JF, Kleiman NS, Hammoud T, Booth JE, Sapp SK, Topol EJ. · Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. · Circulation. · Pubmed #10604884 links to  free full text

Abstract: BACKGROUND: Stenting likely decreases the need for target-vessel revascularization procedures in diabetic patients compared with balloon angioplasty. However, the efficacy of stenting with platelet glycoprotein IIb/IIIa blockade has not yet been assessed in diabetics. METHODS AND RESULTS: We analyzed the outcomes of 491 diabetic patients within the multicenter Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial (EPISTENT). Diabetic patients were a prospectively defined subset: 173 were randomized to stent-placebo, 162 to stent-abciximab, and 156 to balloon angioplasty-abciximab. The main end point for this analysis was combined 6-month death, myocardial infarction (MI), or target-vessel revascularization (TVR). The composite end point occurred in 25.2% of stent-placebo, 23.4% of balloon-abciximab, and 13.0% of stent-abciximab patients (P=0.005). Abciximab therapy, irrespective of revascularization strategy (stent or balloon angioplasty), resulted in a significant reduction in the 6-month death or MI rate: 12.7% for stent-placebo, 7.8% for balloon angioplasty-abciximab, and 6.2% for the stent-abciximab group (P=0.029). The 6-month TVR rate was 16.6% for stent-placebo, 18.4% for balloon-abciximab, and 8.1% for stent-abciximab (P=0.021). Compared with stent-placebo, stent-abciximab therapy was associated with a significant increase in angiographic net gain (0.88 versus 0.55 mm; P=0.011) and a decrease in the late loss index (0.40 versus 0.60 mm; P=0.061). The 1-year mortality rate for diabetics was 4.1% for stent-placebo and 1. 2% for stent-abciximab patients (P=0.11). CONCLUSIONS: The combination of stenting and abciximab therapy among diabetics resulted in a significant reduction in 6-month rates of death, MI, and TVR compared with stent-placebo or balloon-abciximab therapy.

Mukherjee D, Bhatt DL, Roe MT, Patel V, Ellis SG. · Department of Cardiology, The Cleveland Clinic Foundation, Ohio 44195, USA. · Am J Cardiol. · Pubmed #10482164 No free full text.

Abstract: This study examines the proportion of patients with ischemic heart disease who may be candidates for the newer modalities of revascularization. A significant proportion (approximately 5%) of patients who undergo coronary angiography at tertiary referral centers may be eligible for newer methods of therapy.

Lincoff AM, Califf RM, Moliterno DJ, Ellis SG, Ducas J, Kramer JH, Kleiman NS, Cohen EA, Booth JE, Sapp SK, Cabot CF, Topol EJ. · Department of Cardiology, Cleveland Clinic Foundation, OH 44195, USA. · N Engl J Med. · Pubmed #10423466 links to  free full text

Abstract: BACKGROUND: Inhibition of the platelet glycoprotein IIb/IIIa receptor with the monoclonal-antibody fragment abciximab reduces the acute ischemic complications associated with percutaneous coronary revascularization, whereas coronary-stent implantation reduces restenosis. We conducted a trial to determine the efficacy of abciximab and stent implantation in improving long-term outcome. METHODS: A total of 2399 patients were randomly assigned to stent implantation and placebo, stent implantation and abciximab, or balloon angioplasty and abciximab. The patients were followed for six months. RESULTS: At six months, the incidence of the composite end point of death or myocardial infarction was 11.4 percent in the group that received a stent and placebo, as compared with 5.6 percent in the group that received a stent and abciximab (hazard ratio, 0.47; 95 percent confidence interval, 0.33 to 0.68; P<0.001) and 7.8 percent in the group assigned to balloon angioplasty and abciximab (hazard ratio, 0.67; 95 percent confidence interval, 0.49 to 0.92; P=0.01). The hazard ratio for stenting plus abciximab as compared with angioplasty plus abciximab was 0.70 (95 percent confidence interval, 0.48 to 1.04; P=0.07). The rate of repeated revascularization of the target vessel was 10.6 percent in the stent-plus-placebo group, as compared with 8.7 percent in the stent-plus-abciximab group (hazard ratio, 0.82; 95 percent confidence interval, 0.59 to 1.13; P=0.22) and 15.4 percent in the angioplasty-plus-abciximab group (hazard ratio, 1.49; 95 percent confidence interval, 1.13 to 1.97; P=0.005). The hazard ratio for stenting plus abciximab as compared with angioplasty plus abciximab was 0.55 (95 percent confidence interval, 0.41 to 0.74; P<0.001). Among patients with diabetes, the combination of abciximab and stenting was associated with a lower rate of repeated target-vessel revascularization (8.1 percent) than was stenting and placebo (16.6 percent, P=0.02) or angioplasty and abciximab (18.4 percent, P=0.008). CONCLUSIONS: For coronary revascularization, abciximab and stent implantation confer complementary long-term clinical benefits.

Marso SP, Ellis SG, Tuzcu M, Whitlow PL, Franco I, Raymond RE, Topol EJ. · Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195, USA. · J Am Coll Cardiol. · Pubmed #10193727 No free full text.

Abstract: OBJECTIVES: The aims of this study were to compare mortality and clinical events following percutaneous coronary intervention (PCI) between nondiabetics and diabetics with and without proteinuria. BACKGROUND: Diabetics have increased rates of late myocardial infarction, repeat revascularization and mortality when compared with nondiabetics following PCI. Proteinuria is a marker for diabetic nephropathy and potentially a surrogate marker for advanced atherosclerosis. It is unknown if proteinuria is a predictor of outcome in diabetics following PCI. METHODS: We performed an observational study of 2,784 patients who underwent PCI at the Cleveland Clinic between January 1993 and December 1995. There were 2,247 nondiabetics and 537 diabetics with urinalysis and follow-up data available (proteinuria n = 217, nonproteinuria n = 320). The diabetic proteinuria group was further prospectively stratified into low concentration (n = 182) and high concentration (n = 35). The end points were all-cause mortality and the composite end point of death, nonfatal myocardial infarction (MI) and need for revascularization. RESULTS: The mean follow-up time was 20.2 months. The two-year mortality rate was 7.3% and 13.5% for nondiabetics and diabetics, respectively (p < 0.001). The two-year mortality rate was 9.1% and 20.3% for the nonproteinuria and proteinuria groups, respectively (p < 0.001). There was a graded increase in mortality comparing the diabetic group. The two-year mortality rate was 9.1%, 16.2% and 43.1% for the nonproteinuria, low concentration and high concentration groups, respectively (p < 0.001). The difference in survival between the nondiabetic and nonproteinuric diabetics was not significant (p = 0.8). CONCLUSIONS: The presence of proteinuria is the key determinant of risk following PCI for diabetics. Diabetics without evidence of proteinuria have similar survival compared with nondiabetics.

Shishehbor MH, Amini R, Raymond RE, Bavry AA, Brener SJ, Kapadia SR, Whitlow PL, Ellis SG, Bhatt DL. · Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA. · Am Heart J. · Pubmed #18513522 No free full text.

Abstract: BACKGROUND: The short-term and long-term safety and efficacy of paclitaxel versus sirolimus-overlapping drug-eluting stents (DES) is unknown. We sought to examine the clinical consequences of overlapping sirolimus versus paclitaxel DES. METHODS: We reviewed catheterization reports from April 2003 to May 2005 for all patients who underwent percutaneous coronary revascularization with DES. All patients were followed-up for at least 1 year. Patients were included if they received only 2 single-type overlapping stent (eg, sirolimus-sirolimus) during the index procedure. The end points included early (inhospital and 30-day) and late composite of all-cause mortality, stent thrombosis, myocardial infarction, and target lesion revascularization. RESULTS: A total of 282 individuals met our study criteria. Of these, 188 had sirolimus and 94 had paclitaxel-overlapping DES. There were 78 events for a median follow-up of 24 months for the composite end point. No statistically significant differences between overlapping sirolimus and paclitaxel DES were seen for inhospital, 30-day (16% vs 23%, respectively; P = .13), and long-term (25% vs 33%, respectively; P = .16) composite end points. In addition, in Kaplan-Meier and Cox proportional hazard analysis, no significant differences for the composite end point were noted. CONCLUSIONS: In this analysis, there were no significant differences in safety or efficacy between the 2 types of overlapping DES. Trends toward more events with overlapping paclitaxel stents should be evaluated in an adequately powered randomized controlled trial.

Kirtane AJ, Ellis SG, Dawkins KD, Colombo A, Grube E, Popma JJ, Fahy M, Leon MB, Moses JW, Mehran R, Stone GW. · Columbia University Medical Center and the Cardiovascular Research Foundation, New York, New York 10022, USA. · J Am Coll Cardiol. · Pubmed #18279734 No free full text.

Abstract: OBJECTIVES: We sought to examine the safety and efficacy of paclitaxel-eluting stents (PES) in patients with diabetes mellitus (DM). BACKGROUND: Compared with patients without DM, patients with DM undergoing percutaneous coronary intervention are at increased risk for mortality and restenosis. The safety of drug-eluting stents in diabetic patients has recently been called into question by a published meta-analysis of randomized trials. METHODS: Patient-level data were pooled from 5 prospective, double-blind, randomized trials of PES versus bare-metal stents (BMS) (n = 3,513). Safety and efficacy outcomes through 4 years of follow-up were assessed among the 827 randomized patients (23.6%) with DM. RESULTS: Patients treated with PES and BMS has similar baseline characteristics among both the diabetic and nondiabetic cohorts within these trials. At 4-year follow-up, there were no significant differences between PES and BMS among diabetic patients in the rates of death (8.4% vs. 10.3%, respectively, p = 0.61), myocardial infarction (6.9% vs. 8.9%, p = 0.17), or stent thrombosis (1.4% vs. 1.2%, p = 0.92). Treatment of diabetic patients with PES compared with treatment with BMS was associated with a significant and durable reduction in target lesion revascularization over the 4-year follow-up period (12.4% vs. 24.7%, p < 0.0001). The relative safety and efficacy of PES compared with the relative safety and efficacy of BMS in diabetic patients extended to both those requiring and not requiring insulin. CONCLUSIONS: In these 5 randomized trials in which patients with single, primarily noncomplex lesions were enrolled, treatment with PES compared with treatment with BMS was safe and effective, resulting in markedly lower rates of target lesion revascularization at 4 years, with similar rates of death, myocardial infarction, and stent thrombosis.

Brener SJ, Galla JM, Bryant R, Sabik JF, Ellis SG. · Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA. · Am J Cardiol. · Pubmed #18178401 No free full text.

Abstract: Coronary artery bypass grafting (CABG) has been the recommended treatment for patients with significant left main coronary artery (LMCA) stenosis. Advances in stent technology have invigorated investigations into the suitability of a percutaneous approach for these patients. Favorable short-term results from nonrandomized comparisons were previously reported. Patients (n = 97) who underwent percutaneous coronary intervention for severe (>70%) LMCA stenosis were matched in a 1:2 ratio with a cohort that underwent surgical revascularization (n = 190). The groups were similar for age, gender, European System for Cardiac Operative Risk Evaluation, left ventricular ejection fraction, history of myocardial infarction, and presence of renal disease. Kaplan-Meier estimates of 3-year mortality were similar for the PCI and CABG groups at 80% (95% confidence interval [CI] 68 to 88) versus 85% (95% CI 79 to 89, p = 0.14), respectively. Propensity score-adjusted 3-year mortality did not differ between groups (p = 0.22). Multivariable modeling identified only higher European System for Cardiac Operative Risk Evaluation (hazard rate 1.33, 95% CI 1.16 to 1.54, p <0.001) and the presence of diabetes mellitus (hazard rate 1.96, 95% CI 1.24 to 3.09, p = 0.004) as independent risks of mortality at 3 years. In conclusion, patients who underwent percutaneous revascularization of severe LMCA stenosis appeared to have 3-year survival equivalent to those who underwent CABG. Diabetes mellitus and advanced co-morbidity were the principal determinants of survival. These findings support the need for randomized trials with adequate follow-up to compare the 2 approaches.

Ellis SG, Kandzari D, Kereiakes DJ, Pichard A, Huber K, Resnic F, Yakubov S, Callahan K, Borgman M, Cohen SA. · Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA. · J Invasive Cardiol. · Pubmed #17906340 links to  free full text

Abstract: BACKGROUND: Although the increased utilization of drug-eluting stents is well supported by multiple studies with clinical trial data for many patient and lesion subsets, their use to treat diseased saphenous vein graft (SVG) lesions is much less well substantiated. We sought to ascertain and compare 12-month target vessel revascularization (TVR) rates for sirolimus-eluting Cyphertrade mark stents and bare-metal stents (BMS) when utilized to treat stenoses in diseased SVGs. METHODS: Therefore, we conducted a multicenter matched-control study in patients treated for de novo SVG lesions with Cypher or BMS, matching for reference vessel diameter, stent length, diabetes and number of stents utilized. The primary study endpoint was TVR at 12 months. RESULTS: Three hundred and fifty patients were matched, with patient age = 69 +/- 9 years, 77% male, 39% diabetics, SVG age = 119 +/- 75 months, reference vessel diameter = 3.3 +/- 0.4 mm, target lesion length = 17.4 +/- 8.4 mm (p = NS for all between-group comparisons). Twelve-month TVR was modestly reduced with Cypher stenting (6.8% vs. 11.8%; p = 0.14) due to a trend toward a reduction in binary restenosis (7.4% vs. 13.6%; p = 0.08). Twelve-month survival was 95.3% and 96.4% in the Cypher and BMS groups, respectively (p = 0.79). CONCLUSIONS: Cypher stents appear to modestly reduce TVR without apparent safety risk compared with BMS when applied to the treatment of diseased SVGs. In conjunction with other available studies, these data support Cypher stent use in this setting.

Doonan AL, Karha J, Carrigan TP, Bavry AA, Begelman SM, Ellis SG, Yadav J, Bhatt DL. · Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA. · Am J Cardiol. · Pubmed #17884367 No free full text.

Abstract: Left main (LM) coronary disease, carotid artery disease, and peripheral arterial disease each reflects advanced atherosclerosis. The frequency of their coexistence in the same patient has not been fully elucidated. All coronary angiograms obtained at the Cleveland Clinic from November 2003 to October 2005 were analyzed for presence of LM stenosis > or =50%. Patients with previous coronary artery bypass graft surgery were excluded. Patients with available carotid ultrasound and ankle-brachial indexes formed the analysis cohorts. A total of 10,298 coronary angiograms were obtained in 9,715 patients. There were 186 patients with LM disease and 1,913 patients without LM disease with carotid artery ultrasound data. There were 29 patients with LM disease and 604 patients without LM disease with available ankle-brachial indexes. Patients with significant LM disease more frequently had associated carotid stenosis > or =60% compared with patients without LM disease (31.2% vs 15.2%, p <0.0001). Patients with LM disease had lower mean ankle-brachial indexes compared with patients without LM disease (0.78 vs 0.87, p = 0.042). In conclusion, compared with patients without LM disease, patients with LM disease have a higher burden of advanced atherosclerosis as evidenced by a higher prevalence of significant carotid stenosis and lower ankle-brachial indexes.

Luke MM, Kane JP, Liu DM, Rowland CM, Shiffman D, Cassano J, Catanese JJ, Pullinger CR, Leong DU, Arellano AR, Tong CH, Movsesyan I, Naya-Vigne J, Noordhof C, Feric NT, Malloy MJ, Topol EJ, Koschinsky ML, Devlin JJ, Ellis SG. · Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502, USA. · Arterioscler Thromb Vasc Biol. · Pubmed #17569884 links to  free full text

Abstract: OBJECTIVES: The purpose of this study was to identify genetic variants associated with severe coronary artery disease (CAD). METHODS AND RESULTS: We used 3 case-control studies of white subjects whose severity of CAD was assessed by angiography. The first 2 studies were used to generate hypotheses that were then tested in the third study. We tested 12,077 putative functional single nucleotide polymorphisms (SNPs) in Study 1 (781 cases, 603 controls) and identified 302 SNPs nominally associated with severe CAD. Testing these 302 SNPs in Study 2 (471 cases, 298 controls), we found 5 (in LPA, CALM1, HAP1, AP3B1, and ABCG2) were nominally associated with severe CAD and had the same risk alleles in both studies. We then tested these 5 SNPs in Study 3 (554 cases, 373 controls). We found 1 SNP that was associated with severe CAD: LPA I4399M (rs3798220). LPA encodes apolipoprotein(a), a component of lipoprotein(a). I4399M is located in the protease-like domain of apolipoprotein(a). Compared with noncarriers, carriers of the 4399M risk allele (2.7% of controls) had an adjusted odds ratio for severe CAD of 3.14 (confidence interval 1.51 to 6.56), and had 5-fold higher median plasma lipoprotein(a) levels (P=0.003). CONCLUSIONS: The LPA I4399M SNP is associated with severe CAD and plasma lipoprotein(a) levels.

Shishehbor MH, Zhang R, Medina H, Brennan ML, Brennan DM, Ellis SG, Topol EJ, Hazen SL. · Department of Cell Biology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA. · Free Radic Biol Med. · Pubmed #17145556 links to  free full text

Abstract: Oxidant stress is widely believed to participate in cardiovascular disease pathogenesis. However, progress in defining appropriate systemic antioxidant targeted therapies has been hindered by uncertainty in defining clinically relevant systemic oxidant stress measures. In a case control study, 50 subjects with CAD (>50% stenosis in one or more major coronary vessels) and 54 without CAD (<30% stenosis in all major coronary vessels) were tested. Plasma was isolated and stored under conditions designed to prevent artificial lipid peroxidation. Systemic levels of multiple (n=9) specific fatty acid oxidation products including individual hydroxyoctadecadienoic acids (HODEs), hydroxyeicosatetraenoic acids (HETEs), and F(2)-isoprostanes were simultaneously measured by high-performance liquid chromatography (HPLC) with on-line tandem mass spectrometry, along with traditional risk factors and C-reactive protein (CRP) levels. Of the markers monitored, only 9-HETE and F(2)-isoprostanes, both products of free radical-mediated arachidonic acid oxidation, were significantly elevated in patients with angiographically defined CAD (9-HETE, 8.7 +/- 4 vs 6.8 +/- 4 micromol/mol arachidonate, P = 0.011; and F(2)-isoprostanes, 9.4 +/- 5 vs 6.2 +/- 3 micromol/mol arachidonate, P < 0.001). In multivariable analyses with simultaneous adjustment for Framingham risk score and C-reactive protein, 9-HETE (4th quartile OR = 4.8, 95% CI=1.3 to 17.1; P = 0.016) and F(2)-isoprostanes (4th quartile OR=9.7, 95% CI=2.56 to 36.9; P < 0.001) remained strong and independent predictors of CAD risk. Systemic levels of 9-HETE and F(2)-isoprostanes are independently associated with angiographic evidence of CAD and appear superior to other specific oxidation products of arachidonic and linoleic acids as predictors of the presence of angiographically evident coronary artery disease.

Weisz G, Leon MB, Holmes DR, Kereiakes DJ, Clark MR, Cohen BM, Ellis SG, Coleman P, Hill C, Shi C, Cutlip DE, Kuntz RE, Moses JW. · Cardiovascular Research Foundation and Columbia University Medical Center, New York, New York 10032, USA. · J Am Coll Cardiol. · Pubmed #16580520 No free full text.

Abstract: OBJECTIVES: 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. BACKGROUND: 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). METHODS: Patients with de novo native coronary artery lesions randomized to either SES (533 patients) or control BMS (525 patients) were followed for two years. RESULTS: 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. CONCLUSIONS: 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.

Brener SJ, Lytle BW, Casserly IP, Ellis SG, Topol EJ, Lauer MS. · Department of Cardiovascular Medicine, Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk F-25, Cleveland, OH 44195 USA. · Eur Heart J. · Pubmed #16272211 links to  free full text

Abstract: AIMS: The optimal revascularization strategy in patients with symptomatic multivessel coronary artery disease (CAD) and previous coronary artery bypass grafting (CABG) remains unknown. METHODS AND RESULTS: We evaluated all patients with previous CABG undergoing isolated, non-emergency multivessel revascularization between 1 January 1995 and 31 December 2000. The analysis concentrated on the independent predictors of the revascularization method, as well as on long-term mortality and its predictors, after calculating a propensity score for the method of revascularization. There were 2191 patients (1487 with reoperation and 704 with percutaneous coronary intervention, PCI) in the study. The most important factors in choosing reoperation were presence of more diseased or occluded grafts, previous infarction, lower ejection fraction (EF), longer interval from first CABG, and more total occlusions of native arteries, as well as absence of a patent mammary graft. The distribution of the propensity score was skewed towards the two extremes. At 5 years, the unadjusted cumulative survival was 79.5% for CABG and 75.3% for PCI, P=0.008. After adjustment for the propensity score for PCI vs. CABG, PCI was associated with a hazard ratio of 1.47 (0.94-2.28), P=0.09. The most powerful predictors of mortality were higher age and lower EF. CONCLUSION: The choice of the revascularization method in patients with previous CABG is dictated mostly by anatomical considerations and less by clinical characteristics. In contrast, clinical characteristics predominantly affect long-term outcome, whereas the method of revascularization has a limited effect. A randomized clinical trial addressing this important segment of the population with ischaemic heart disease is warranted.