Ecaterina Cristea

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.).

Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial Infarction The INFUSE-AMI Randomized Trial

CONTEXT Thrombus embolization during percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) is common and results in suboptimal myocardial perfusion and increased infarct size. Two strategies proposed to reduce distal embolization and improve outcomes after primary PCI are bolus intracoronary abciximab and manual aspiration thrombectomy. OBJECTIVE To determine whether bolus intracoronary abciximab, manual aspiration thrombectomy, or both reduce infarct size in high-risk patients with STEMI. DESIGN, SETTING, AND PATIENTS Between November 28, 2009, and December 2, 2011, 452 patients presenting at 37 sites in 6 countries within 4 hours of STEMI due to proximal or mid left anterior descending artery occlusion undergoing primary PCI with bivalirudin anticoagulation were randomized in an open-label, 2 x 2 factorial design to bolus intracoronary abciximab delivered locally at the infarct lesion site vs no abciximab and to manual aspiration thrombectomy vs no thrombectomy. INTERVENTIONS A 0.25-mg/kg bolus of abciximab was administered at the site of the infarct lesion via a local drug delivery catheter. Manual aspiration thrombectomy was performed with a 6 F aspiration catheter. MAIN OUTCOME MEASURES Primary end point: infarct size (percentage of total left ventricular mass) at 30 days assessed by cardiac magnetic resonance imaging (cMRI) in the abciximab vs no abciximab groups (pooled across the aspiration randomization); major secondary end point: 30-day infarct size in the aspiration vs no aspiration groups (pooled across the abciximab randomization). RESULTS Evaluable cMRI results at 30 days were present in 181 and 172 patients randomized to intracoronary abciximab vs no abciximab, respectively, and in 174 and 179 patients randomized to manual aspiration vs no aspiration, respectively. Patients randomized to intracoronary abciximab compared with no abciximab had a significant reduction in 30-day infarct size (median, 15.1%; interquartile range [IQR], 6.8%-22.7%; n = 181, vs 17.9% [IQR, 10.3%-25.4%]; n = 172; P = .03). Patients randomized to intracoronary abciximab also had a significant reduction in absolute infarct mass (median, 18.7 g [IQR, 7.4-31.3 g]; n = 184, vs 24.0 g [IQR, 12.1-34.2 g]; n = 175; P = .03) but not abnormal wall motion score (median, 7.0 [IQR, 2.0-10.0]; n = 188, vs 8.0 [IQR, 3.0-10.0]; n = 184; P = .08). Patients randomized to aspiration thrombectomy vs no aspiration had no significant difference in infarct size at 30 days (median, 17.0% [IQR, 9.0%-22.8%]; n = 174, vs 17.3% [IQR, 7.1%-25.5%]; n = 179; P = .51), absolute infarct mass (median, 20.3 g [IQR, 9.7-31.7 g]; n = 178, vs 21.0 g [IQR, 9.1-34.1 g]; n = 181; P = .36), or abnormal wall motion score (median, 7.5 [IQR, 2.0-10.0]; n = 186, vs 7.5 [IQR, 2.0-10.0]; n = 186; P = .89). CONCLUSION In patients with large anterior STEMI presenting early after symptom onset and undergoing primary PCI with bivalirudin anticoagulation, infarct size at 30 days was significantly reduced by bolus intracoronary abciximab delivered to the infarct lesion site but not by manual aspiration thrombectomy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00976521.

Nitinol Stent Implantation Versus Balloon Angioplasty for Lesions in the Superficial Femoral Artery and Proximal Popliteal Artery Twelve-Month Results From the RESILIENT Randomized Trial

Background—Controversy still exists regarding the best endovascular treatment strategy for patients with symptomatic disease of the superficial femoral artery. There are conflicting data regarding the benefits of superficial femoral artery stenting and the role of primary stenting compared with balloon angioplasty with provisional stent implantation. Methods and Results—A total of 206 patients from 24 centers in the United States and Europe with obstructive lesions of the superficial femoral artery and proximal popliteal artery and intermittent claudication were randomized to implantation of nitinol stents or percutaneous transluminal angioplasty. The mean total lesion length was 71 mm for the stent group and 64 mm for the angioplasty group. Acute lesion success (<30% residual stenosis) was superior for the stent group compared with the angioplasty group (95.8% versus 83.9%; P<0.01). Twenty-nine (40.3%) patients in the angioplasty group underwent bailout stenting because of a suboptimal angiographic result or flow-limiting dissection. Bailout stenting was treated as a target lesion revascularization and loss of primary patency in the final analysis. At 12 months, freedom from target lesion revascularization was 87.3% for the stent group compared with 45.1% for the angioplasty group (P<0.0001). Duplex ultrasound-derived primary patency at 12 months was better for the stent group (81.3% versus 36.7%; P<0.0001). Through 12 months, fractures occurred in 3.1% of stents implanted. No stent fractures resulted in loss of patency or target lesion revascularization. Conclusions—In this multicenter trial, primary implantation of a self-expanding nitinol stent for moderate-length lesions in the superficial femoral artery and proximal popliteal artery was associated with better acute angiographic results and improved patency compared with balloon angioplasty alone. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00673985.

Nitinol Stent Implantation Versus Balloon Angioplasty for Lesions in the Superficial Femoral Artery and Proximal Popliteal ArteryClinical Perspective

Background—Controversy still exists regarding the best endovascular treatment strategy for patients with symptomatic disease of the superficial femoral artery. There are conflicting data regarding the benefits of superficial femoral artery stenting and the role of primary stenting compared with balloon angioplasty with provisional stent implantation. Methods and Results—A total of 206 patients from 24 centers in the United States and Europe with obstructive lesions of the superficial femoral artery and proximal popliteal artery and intermittent claudication were randomized to implantation of nitinol stents or percutaneous transluminal angioplasty. The mean total lesion length was 71 mm for the stent group and 64 mm for the angioplasty group. Acute lesion success (<30% residual stenosis) was superior for the stent group compared with the angioplasty group (95.8% versus 83.9%; P<0.01). Twenty-nine (40.3%) patients in the angioplasty group underwent bailout stenting because of a suboptimal angiographic result or flow-limiting dissection. Bailout stenting was treated as a target lesion revascularization and loss of primary patency in the final analysis. At 12 months, freedom from target lesion revascularization was 87.3% for the stent group compared with 45.1% for the angioplasty group (P<0.0001). Duplex ultrasound-derived primary patency at 12 months was better for the stent group (81.3% versus 36.7%; P<0.0001). Through 12 months, fractures occurred in 3.1% of stents implanted. No stent fractures resulted in loss of patency or target lesion revascularization. Conclusions—In this multicenter trial, primary implantation of a self-expanding nitinol stent for moderate-length lesions in the superficial femoral artery and proximal popliteal artery was associated with better acute angiographic results and improved patency compared with balloon angioplasty alone. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00673985.

Non–Polymer-Based Paclitaxel-Coated Coronary Stents for the Treatment of Patients With De Novo Coronary Lesions: Angiographic Follow-Up of the DELIVER Clinical Trial

Background—Paclitaxel, a microtubule-stabilizing compound with potent antitumor activity, has been shown to inhibit smooth muscle cell proliferation and migration. The DELIVER trial was a prospective, randomized, blinded, multicenter clinical evaluation of the non–polymer-based paclitaxel-coated ACHIEVE stent compared with the stainless steel Multi-Link (ML) PENTA stent. Methods and Results—A total of 1043 patients with focal de novo coronary lesions, <25 mm in length, in 2.5- to 4.0-mm vessels were randomized (ACHIEVE n=524; ML PENTA n=519). Angiographic follow-up was performed in a subset of 442 patients (ACHIEVE n=228; ML PENTA n=214). Prespecified end points were a 40% reduction in target-vessel failure at 9 months (primary clinical end point) and a 50% reduction in binary restenosis at 8 months (major secondary end point). Baseline clinical characteristics were comparable between the groups. Patients in ACHIEVE had more type C lesions and a larger reference diameter. At follow-up, stent late loss was 0.81 versus 0.98 mm (P =0.003), stent binary restenosis was 14.9% versus 20.6% (P =0.076), and target-vessel failure was 11.9% versus 14.5% (P =0.12) for ACHIEVE and ML PENTA, respectively. Conclusions—The ACHIEVE paclitaxel-coated stent decreased neointimal proliferation compared with the bare-metal PENTA stent; however, this reduction was insufficient to meet the prespecified primary end point of target-vessel failure and the secondary end point of binary restenosis.

Frequency and Predictors of Stent Thrombosis After Percutaneous Coronary Intervention in Acute Myocardial Infarction

Background— Concerns persist regarding the risk of stent thrombosis in the setting of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Methods and Results— The Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial included 3602 patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention who were randomized to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) (n=1802) versus bivalirudin monotherapy (n=1800). Stents were implanted in 3202 patients, including 2261 who received drug-eluting stents and 861 who received only bare metal stents. Definite or probable stent thrombosis within 2 years occurred in 137 patients (4.4%), including 28 acute events (0.9%), 49 subacute events (1.6%), 32 late events (1.0%), and 33 very late events (1.1%). The 2-year cumulative rates of stent thrombosis were 4.4% with both drug-eluting stents and bare metal stents (P=0.98) and 4.3% versus 4.6% in patients randomized to bivalirudin monotherapy versus heparin plus a GPI, respectively (P=0.73). Acute stent thrombosis occurred more frequently in patients assigned to bivalirudin compared with heparin plus a GPI (1.4% versus 0.3%; P<0.001), whereas stent thrombosis after 24 hours occurred less frequently in patients with bivalirudin compared with heparin plus a GPI (2.8% versus 4.4%; P=0.02). Prerandomization heparin and a 600-mg clopidogrel loading dose were independent predictors of reduced acute and subacute stent thrombosis, respectively. Conclusions— Stent thrombosis is not uncommon within the first 2 years after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction, and occurs with similar frequency in patients receiving drug-eluting stents versus bare metal stents and bivalirudin alone versus heparin plus a GPI. Optimizing adjunct pharmacology including early antithrombin therapy preloading with a potent antiplatelet therapy may further reduce stent thrombosis in ST-segment elevation myocardial infarction. Clinical Trial Registration:— http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Gender Differences in Outcomes After Primary Angioplasty Versus Primary Stenting With and Without Abciximab for Acute Myocardial Infarction Results of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Trial

Background—Women with acute myocardial infarction (AMI) undergoing primary angioplasty have higher rates of morbidity and mortality than do men. Whether contemporary interventional treatment strategies have improved outcomes for women compared with men is unknown. Methods and Results—In the CADILLAC trial, 2082 patients (27% women) with AMI within 12 hours of symptom onset were randomized to balloon angioplasty (PTCA; n=518), PTCA+abciximab (n=528), stenting (n=512), and stenting+abciximab (n=524). As compared with men, women had a lower body surface area; had a greater prevalence of diabetes, hypertension, and hyperlipidemia; experienced significant delays to treatment; and had better baseline and final TIMI grade 3 flows. Unadjusted 1-year event rates were higher for women, including death (7.6% versus 3.0%, P<0.001), ischemic target-vessel revascularization (TVR; 16.7% versus 12.1%, P=0.006), and major adverse cardiac events (MACE; 23.9% versus 15.3%, P<0.001). Female gender was an independent predictor of MACE and bleeding complications, although comorbid risk factors and body surface area but not gender predicted 1-year death. For women, primary stenting resulted in a reduction in 1-year MACE from 28.1% to 19.1% (P=0.01) and in ischemic TVR from 20.4% to 10.8% (P=0.002) compared with PTCA. The addition of abciximab to primary stenting significantly reduced the 30-day ischemic TVR without increasing bleeding or stroke rates. Conclusions—The higher mortality rate in women compared with men after interventional treatment for AMI may be explained by differences in body size and clinical risk factors, although female gender remains an important independent determinant of overall adverse outcomes. For women in the CADILLAC trial, the addition of abciximab reduced 30-day TVR without increasing bleeding risk, and primary stenting reduced 1-year TVR and MACE rates compared with PTCA.

Prognostic Value of the SYNTAX Score in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention Analysis From the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) Trial

OBJECTIVES We sought to investigate the predictive value of the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score (SS) for risk assessment of 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention (PCI). BACKGROUND In the SYNTAX trial, the SS was effective in risk-stratifying patients with left main and triple-vessel coronary disease, the majority of whom had stable ischemic heart disease. METHODS The SS was determined in 2,627 patients with non-ST-segment elevation acute coronary syndromes undergoing PCI in the angiographic substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) trial. Patients were stratified according to tertiles of the SS: <7 (n = 854), ≥ 7 and <13 (n = 825), and ≥ 13 (n = 948). RESULTS Among patients in the first, second, and third SS tertiles, the 1-year rates of mortality were 1.5%, 1.6%, and 4.0%, respectively (p = 0.0005); the cardiac mortality rates were 0.2%, 0.9%, and 2.7%, respectively (p < 0.0001); the myocardial infarction (MI) rates were 6.3%, 8.3%, and 12.9%, respectively (p < 0.0001); and the target vessel revascularization (TVR) rates were 7.4%, 7.0%, and 9.8%, respectively (p = 0.02). By multivariable analysis, the SS was an independent predictor of 1-year death (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 1.01 to 1.07; p = 0.005), cardiac death (HR: 1.06, 95% CI: 1.03 to 1.09; p = 0.0002), MI (HR: 1.03, 95% CI: 1.02 to 1.05; p < 0.0001), and TVR (HR: 1.03, 95% CI: 1.02 to 1.05; p < 0.0001). The SS affected death, cardiac death, and MI both within the first 30 days after PCI and between 30 days and 1 year, whereas it affected TVR primarily within the first 30 days. The predictive value of an increased SS was consistent among multiple pre-specified subgroups. CONCLUSIONS In patients with non-ST-segment elevation acute coronary syndromes undergoing PCI, the SS is an independent predictor of the 1-year rates of death, cardiac death, MI, and TVR. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158).

Nitinol Stent Implantation vs. Balloon Angioplasty for Lesions in the Superficial Femoral and Proximal Popliteal Arteries of Patients With Claudication: Three-Year Follow-up From the RESILIENT Randomized Trial:

Purpose To evaluate longer outcomes of primary nitinol stenting for the treatment of femoropopliteal lesions up to 15 cm long after these stents were found to have superior short-term patency vs. balloon angioplasty. Methods Two hundred and six patients (143 men; mean age 67 years) with intermittent claudication due to superficial femoral and proximal popliteal artery lesions were randomized (2:1) to treatment with nitinol stents or balloon angioplasty at 24 US and European centers and followed for 3 years. In that time, 15 patients died, 20 withdrew consent, and 10 were lost to follow-up, leaving 161 (78.2%) patients for 36-month assessment. Results The 12-month freedom from target lesion revascularization (TLR) was 87.3% for the stent group vs. 45.2% for the angioplasty group (p<0.0001). At 3 years, there was no difference in survival (90.0% vs. 91.7%, p=0.71) or major adverse events (75.2% vs. 75.2%, p=0.98) between the stent and angioplasty groups. Duplex ultrasound was not mandated after the first year, so stent patency could not be ascertained beyond 1 year, but freedom from TLR at 3 years was significantly better in the stent group (75.5% vs. 41.8%, p<0.0001), as was clinical success (63.2% vs. 17.9%, p<0.0001). At 18 months, a 4.1% (12/291) stent fracture rate was documented. Conclusion In this multicenter trial, primary implantation of a nitinol stent for moderate-length lesions in the femoropopliteal segment of patients with claudication was associated with better long-term results vs. balloon angioplasty alone.

Strut coverage and late malapposition with paclitaxel-eluting stents compared with bare metal stents in acute myocardial infarction: optical coherence tomography substudy of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) Trial.

Background— The safety of drug-eluting stents in ST-segment elevation myocardial infarction (STEMI) continues to be debated. Pathological studies have demonstrated an association between uncovered struts and subsequent stent thrombosis. Optical coherence tomography can detect stent strut coverage in vivo on a micron-scale level. We therefore used optical coherence tomography to examine strut coverage in patients with STEMI treated with paclitaxel-eluting stents (PES) and bare metal stents (BMS). Methods and Results— In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, patients with STEMI were randomized 3:1 to PES or BMS implantation. In a formal substudy, optical coherence tomography at 13 months was performed in 118 consecutive randomized patients (89 PES, 29 BMS) in whom 188 stents were assessed (146 PES and 42 BMS). A total of 44 139 stent struts were analyzed by an independent core laboratory blinded to stent assignment. The primary prespecified end point, the percentage of uncovered stent struts per lesion at follow-up, was 1.1±2.5% in BMS lesions versus 5.7±7.0% in PES lesions (P<0.0001). Malapposed struts were observed in 0.1±0.2% of BMS lesions versus 0.9±2.1% of PES lesions (P=0.0003). Percentage net volume obstruction was 36.0±15.4% with BMS and 19.2±11.3% with PES (P<0.0001). Conclusions— In patients with STEMI undergoing primary percutaneous coronary intervention, implantation of PES as compared with BMS significantly reduces neointimal hyperplasia but results in higher rates of uncovered and malapposed stent struts as assessed by optical coherence tomography at 13-month follow-up. Further studies are required to determine the clinical significance of these findings. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.