Paul C. Gordon

A Clinical Trial Comparing Three Antithrombotic-Drug Regimens after Coronary-Artery Stenting

Background Antithrombotic drugs are used after coronary-artery stenting to prevent stent thrombosis. We compared the efficacy and safety of three antithrombotic-drug regimens — aspirin alone, aspirin and warfarin, and aspirin and ticlopidine — after coronary stenting. Methods Of 1965 patients who underwent coronary stenting at 50 centers, 1653 (84.1 percent) met angiographic criteria for successful placement of the stent and were randomly assigned to one of three regimens: aspirin alone (557 patients), aspirin and warfarin (550 patients), or aspirin and ticlopidine (546 patients). All clinical events reflecting stent thrombosis were included in the prespecified primary end point: death, revascularization of the target lesion, angiographically evident thrombosis, or myocardial infarction within 30 days. Results The primary end point was observed in 38 patients: 20 (3.6 percent) assigned to receive aspirin alone, 15 (2.7 percent) assigned to receive aspirin and warfarin, and 3 (0.5 percent) assigned to rece...

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 ≤28 mm) were randomized 2:1 to EES versus PES. Antiplatelet therapy consisted of aspirin indefinitely and a thienopyridine for ≥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.

Mechanisms of restenosis and redilation within coronary stents—Quantitative angiographic assessment

OBJECTIVES This study was designed to assess the relative contributions of intimal hyperplasia and stent compression to the lumen narrowing seen after intracoronary stenting and to determine whether the lumen enlargement produced by angioplasty of in-stent restenosis results primarily from compression or extrusion of intimal hyperplasia through the stent or from additional stent expansion. BACKGROUND Palmaz-Schatz stent placement outwardly displaces plaque and eliminates elastic vessel recoil to provide a large and smooth lumen. Some degree of late lumen narrowing occurs within each stent and causes significant restenosis (> or = 50% stenosis) in 25% to 30% of treated lesions. It has not been clear, however, whether this narrowing results from stent compression (crush) or from in-stent intimal hyperplasia. Because the Palmaz-Schatz stent has a distinct radiographic shadow, it is possible to determine the late diameter of both the stent and the enclosed vessel lumen to assess the relative contributions of these two processes. METHODS From cineangiograms, initial (after stenting) and late (follow-up) lumen and stent diameters were examined in 55 patients (59 stents, group I) who had both immediate and 6-month (192 +/- 117 days) angiography. Lumen and stent diameter were also examined before and after dilation in 30 patients (30 stents, group II) who underwent angioplasty of severe in-stent restenosis. RESULTS Late loss in minimal lumen diameter was 0.99 +/- 0.87 mm for group I despite only a slight (0.03 +/- 0.23-mm) reduction in the corresponding stent diameter. After redilation for in-stent restenosis, the acute gain in minimal lumen diameter was 1.51 +/- 0.82 mm for group II, again without appreciable increase (0.06 +/- 0.20 mm) in stent diameter. CONCLUSIONS Restenosis after intracoronary Palmaz-Schatz stenting appears to be due predominantly to lumen encroachment by intimal hyperplasia within the stent, with minimal contribution of stent compression. Lumen enlargement after coronary angioplasty of in-stent restenosis appears to be due primarily to compression or extrusion of intimal hyperplasia through the stent, or both, rather than to further stent expansion.

Predictors of Event-Free Survival after Balloon Aortic Valvuloplasty

BACKGROUND Balloon aortic valvuloplasty was developed as an alternative to aortic-valve replacement in selected elderly patients with aortic stenosis. The use of this procedure is limited, however, by a high incidence of restenosis. METHODS Between December 1985 and April 1989, valvuloplasty was performed in 205 patients. We evaluated 40 demographic and hemodynamic variables as univariate predictors of event-free survival by Cox regression analysis and identified independent predictors of event-free survival by stepwise multivariate analysis. RESULTS Early hemodynamic results indicated a decrease in the peak transaortic-valve pressure gradient from 67 +/- 28 to 33 +/- 15 mm Hg after valvuloplasty and an increase in aortic-valve area from 0.6 +/- 0.2 to 0.9 +/- 0.3 cm2 (P less than 0.001 for both comparisons). The rate of event-free survival (defined as survival without recurrent symptoms, repeated valvuloplasty, or aortic-valve replacement) was 18 percent over the mean (+/- SD) follow-up period of 24 +/- 12 months (range, 1 to 47). Significant predictors of event-free survival included the left ventricular ejection fraction and the left ventricular and aortic systolic pressure before valvuloplasty, and the percent reduction in the aortic-valve pressure gradient; the pulmonary-capillary wedge pressure was inversely associated with event-free survival. Although the predicted event-free survival rate for the entire patient group was 50 percent at one year (95 percent confidence interval, 43 to 57 percent) and 25 percent at two years (95 percent confidence interval, 19 to 31 percent), the probability of event-free survival at one year varied between 23 and 65 percent when patients were stratified according to three independent predictors: the aortic systolic pressure, the pulmonary-capillary wedge pressure, and the percent reduction in the peak aortic-valve gradient. CONCLUSIONS The most important predictors of event-free survival after balloon aortic valvuloplasty were related to base-line left ventricular performance. The best long-term results after valvuloplasty were observed among patients who would also have been expected to have excellent long-term results after aortic-valve replacement.

Comparison of Everolimus-Eluting and Paclitaxel-Eluting Coronary Stents in Patients Undergoing Multilesion and Multivessel Intervention

OBJECTIVES We evaluated outcomes following XIENCE V everolimus-eluting stent (EES) compared with the Taxus Express(2) paclitaxel-eluting stent (PES) in patients undergoing multilesion and multivessel intervention. BACKGROUND The optimal revascularization strategy for patients with multivessel disease is unknown. METHODS The SPIRIT III (A Clinical Evaluation of the Investigational Device XIENCE V Everolimus Eluting Coronary Stent System [EECSS] in the Treatment of Subjects With De Novo Native Coronary Artery Lesions) (n = 1,002) and SPIRIT IV (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With De Novo Native Coronary Artery Lesions) (n = 3,690) trials enrolled patients with de novo lesions ≤ 28 mm in length and reference vessel diameter of 2.5 to 3.75 mm. The SPIRIT III trial enrolled patients with a single lesion in 1 or 2 coronary arteries, and the SPIRIT IV trial enrolled patients with up to 2 lesions in 3 different vessels (maximum 2 lesions per vessel). In both trials, patients were randomized 2:1 to EES vs. PES. Clinical outcomes to 1 year were analyzed in patients with single (n = 3,823) versus multiple (n = 765) treated vessels, and in those with single (n = 3,536) versus multiple (n = 1,052) treated lesions. RESULTS Among patients with multivessel disease, EES compared with PES resulted in reduced rates of target vessel myocardial infarction (2.2% vs. 6.1%, p = 0.007) and ischemia-driven target lesion revascularization (4.2% vs. 8.0%, p = 0.04). Among patients undergoing multilesion stenting, EES compared with PES resulted in reduced rates of target vessel myocardial infarction (2.1% vs. 5.4%, p = 0.008) and ischemia-driven target lesion revascularization (3.7% vs. 7.4%, p = 0.01). The absolute benefits of EES versus PES in patients undergoing multivessel or multilesion intervention were greater than in those undergoing single-lesion, single-vessel intervention. CONCLUSIONS The EES compared with PES provided significant improvements in clinical safety and efficacy outcomes. The absolute benefit provided by EES versus PES appears to be proportional to the complexity of coronary disease.

Clinical, procedural, and pharmacologic correlates of acute and subacute stent thrombosis: Results of a multicenter case-control study with 145 thrombosis events

OBJECTIVES The aim of this study was to determine correlates of acute/subacute coronary stent thrombosis among unselected patients treated in the era of routine dual antiplatelet therapy and specifically to investigate the influence of prophylactic administration of glycoprotein IIb/IIIa (GpIIb-IIIa) inhibitors and use of clopidogrel versus ticlopidine on the development of coronary stent thrombosis (ST). BACKGROUND Because of a relative infrequency of ST events and relatively uniform practice patterns within randomized trials, previous studies have had a limited ability to address whether the use of different antiplatelet regimens at the time of coronary stenting is associated with differences in ST. METHODS We performed a multicenter, case-control study to evaluate clinical, angiographic, and pharmacologic/procedural correlates of ST. Between 1996 and 2000, all cases of angiographically-confirmed ST (n = 145) among patients receiving dual antiplatelet therapy were identified from 10 participating clinical sites and were matched with a control without ST randomly selected from the same institution. RESULTS Multivariable conditional logistic regression identified higher pre-procedure platelet count, stenting for acute myocardial infarction, use of a coil or self-expanding stent, and overt angiographic thrombus prior to the procedure, as independent predictors of ST (all P < .05). After adjusting for these factors, the use of clopidogrel (vs ticlopidine) was independently associated with an increased risk of ST (OR 2.1, 95% CI 1.0-4.1, P = .04). The use of prophylactic glycoprotein IIb/IIIa inhibitors was not associated with reduced ST in the overall analysis, but appeared to confer some protection against ST within the first 24 hours post procedure (OR 0.5 [95% CI 0.2-1.1] for ST during first day, OR 1.7 [95% CI 0.7-4.3] for ST on subsequent days). CONCLUSION Both biologic and pharmacologic factors are independently associated with acute/subacute ST. The association between clopidogrel use (vs ticlopidine) and increased ST in this analysis requires confirmation in adequately powered clinical trials and suggests a potential role for newer and more potent antiplatelet agents.

Randomized Trial of Bicarbonate or Saline Study for the Prevention of Contrast-Induced Nephropathy in Patients with CKD

BACKGROUND AND OBJECTIVES Sodium bicarbonate has been proposed for protection of the kidney from contrast-induced AKI (CIAKI). However, the effects of bicarbonate on long-term important clinical outcomes are uncertain. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In a prospective, double-blind, multicenter randomized clinical trial, 391 patients with an eGFR<45 ml/min per 1.73 m(2) undergoing elective coronary or peripheral angiography were randomized to an infusion with a high dose of isotonic sodium bicarbonate (target 2.0 mEq/kg) or a similar molar amount of isotonic sodium chloride. The primary outcome was a composite of mortality, dialysis, or a sustained 20% reduction in eGFR at 6 months. RESULTS There were 391 patients enrolled between March 2010 and May 2012. The incidence of the primary outcome was 14.9% in the bicarbonate group and 16.3% in the control group in the intention-to-treat population (P=0.78). There was also no difference in the incidence of CIAKI between the treatment groups (14.5% versus 12.1%, respectively; P=0.20). CIAKI was associated with a higher incidence of sustained loss of kidney function at 6 months compared with those without CIAKI (21.2% versus 7.7%, respectively; P=0.06). CONCLUSIONS High-dose sodium bicarbonate infusion in patients with eGFR<45 ml/min per 1.73 m(2) undergoing angiography did not demonstrate a difference in incidence of the composite of death, dialysis, or sustained 6-month reduction in eGFR or CIAKI compared with sodium chloride.

An Angiographic and Intravascular Ultrasound Study of the Left Anterior Descending Coronary Artery in Takotsubo Cardiomyopathy

The precise cause of takotsubo cardiomyopathy (TC) remains controversial. Plaque rupture with transient thrombotic occlusion of a transapical left anterior descending coronary artery (LAD) has been advanced as a potential mechanism. To explore this hypothesis, the investigators analyzed data from 11 patients prospectively enrolled in the Rhode Island Takotsubo Cardiomyopathy Registry who underwent coronary angiography and intravascular ultrasound evaluation of the LAD during their initial presentation. Despite the presence of nonobstructive coronary artery disease, no culprit lesion was identified in any patient. Similarly, the course of the LAD failed to account for the characteristic left ventricular apical ballooning seen in TC. In conclusion, an atherosclerotic coronary lesion in the LAD causing an aborted myocardial infarction may not be the primary underlying cause of TC, and nonobstructive coronary artery disease and TC may coexist without a direct causal association.

Evaluation of the effects of everolimus-eluting and paclitaxel-eluting stents on target lesions with jailed side branches: 2-year results from the SPIRIT III randomized trial†

Objective: To evaluate whether an everolimus‐eluting stent (EES) with thinner stent struts and polymer results in less periprocedural myonecrosis and adverse outcomes. Background: Higher periprocedural myocardial infarction (MI) rates have been reported with the TAXUS® EXPRESS2 paclitaxel‐eluting stent (PES) compared to the bare metal EXPRESS2® stent due to more frequent side branch compromise, presumably attributable to the thickness of the stent/polymer on the PES. Methods: In the SPIRIT III trial, we identified 113 patients in the XIENCE V® EES group and 63 patients in the TAXUS EXPRESS2 PES group who met the criteria of having a lesion with a jailed side branch (<2 mm diameter, and <50% stenosis). Two‐year clinical outcomes were evaluated. Results: A periprocedural increase in Creatine Kinase‐MB >1× upper normal level occurred in 9.0% of EES compared to 29.7% of PES patients with jailed side branches, P = 0.01. Through 2 years, major adverse cardiac events (MACE; cardiac death, MI, or target lesion revascularization [TLR]) occurred in 6.8% of EES and 19.0% of PES jailed side branch patients (P = 0.03), with numerically lower rates of MI (2.9% vs. 10.3%, P = 0.07) and TLR (3.9% vs. 10.3%, P = 0.17) in the EES group, with comparable rates of cardiac death (1.9% vs. 1.7%, P = 1.00). Conclusions: In this post‐hoc analysis of the SPIRIT III RCT, patients undergoing stenting of target lesions with jailed side branches with the thin strut and polymer XIENCE V EES compared to the thicker strut TAXUS PES had lower rates of MACE through 2 years due to fewer MIs and TLRs.

Impact of Drug Eluting Stent Length on Outcomes of Percutaneous Coronary Intervention (from the EVENT Registry)

In randomized trials, longer drug-eluting stent (DES) length has been associated with adverse clinical events. We used data from the EVENT registry to examine the impact of DES length on outcomes in routine clinical practice. We identified 5,425 unselected consecutive patients from the EVENT registry who had a single vessel treated with DES for nonemergency indications from 2004 through 2007. The association between stented length and short- and long-term outcomes was analyzed in ordinal categories (<15, 15 to 19, 20 to 24, and >24 mm) and as a continuous variable. There were few differences in baseline characteristics across categories. At 1 year, there was a stepwise increase in major adverse cardiac events (composite of death, myocardial infarction [MI], and target lesion revascularization [TLR]) with increasing stent length (8.0%, 10.1%, 11.8%, and 14.8%, p <0.001) and a similar relation with TLR (3.0%, 3.1%, 3.3%, and 5.0%, p = 0.02). After adjusting for demographic, clinical, angiographic, and treatment characteristics, longer stent length remained associated with 1-year major adverse cardiac events (adjusted hazard ratio 1.17 per 10-mm increase stent length) and TLR (hazard ratio 1.20 per 10 mm), but not with stent thrombosis. In conclusion, longer DES length is associated with increased adverse events, predominantly periprocedural MI, but also an increased rate of TLR.