Robert J. Applegate

Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease?

To help determine if coronary angiography can predict the site of a future coronary occlusion that will produce a myocardial infarction, the coronary angiograms of 42 consecutive patients who had undergone coronary angiography both before and up to a month after suffering an acute myocardial infarction were evaluated. Twenty-nine patients had a newly occluded coronary artery. Twenty-five of these 29 patients had at least one artery with a greater than 50% stenosis on the initial angiogram. However, in 19 of 29 (66%) patients, the artery that subsequently occluded had less than a 50% stenosis on the first angiogram, and in 28 of 29 (97%), the stenosis was less than 70%. In every patient, at least some irregularity of the coronary wall was present on the first angiogram at the site of the subsequent coronary obstruction. In only 10 of the 29 (34%) did the infarction occur due to occlusion of the artery that previously contained the most severe stenosis. Furthermore, no correlation existed between the severity of the initial coronary stenosis and the time from the first catheterization until the infarction (r2 = 0.0005, p = NS). These data suggest that assessment of the angiographic severity of coronary stenosis may be inadequate to accurately predict the time or location of a subsequent coronary occlusion that will produce a myocardial infarction.

Safety and Efficacy of Drug-Eluting and Bare Metal Stents Comprehensive Meta-Analysis of Randomized Trials and Observational Studies

Background— The safety and efficacy of drug-eluting stents (DES) among more generalized “real-world” patients than those enrolled in pivotal randomized controlled trials (RCTs) are controversial. We sought to perform a meta-analysis of DES studies to estimate the relative impact of DES versus bare metal stents (BMS) on safety and efficacy end points, particularly for non–Food and Drug Administration–labeled indications. Methods and Results— Comparative DES versus BMS studies published or presented through February 2008 with ≥100 total patients and reporting mortality data with cumulative follow-up of ≥1 year were identified. Data were abstracted from studies comparing DES with BMS; original source data were used when available. Data from 9470 patients in 22 RCTs and from 182 901 patients in 34 observational studies were included. RCT and observational data were analyzed separately. In RCTs, DES (compared with BMS) were associated with no detectable differences in overall mortality (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.81 to 1.15; P=0.72) or myocardial infarction (HR, 0.95; 95% CI, 0.79 to 1.13; P=0.54), with a significant 55% reduction in target vessel revascularization (HR, 0.45; 95% CI, 0.37 to 0.54; P<0.0001); point estimates were slightly lower in off-label compared with on-label analyses. In observational studies, DES were associated with significant reductions in mortality (HR, 0.78; 95% CI, 0.71 to 0.86), myocardial infarction (HR, 0.87; 95% CI, 0.78 to 0.97), and target vessel revascularization (HR, 0.54; 95% CI, 0.48 to 0.61) compared with BMS. Conclusions— In RCTs, no significant differences were observed in the long-term rates of death or myocardial infarction after DES or BMS use for either off-label or on-label indications. In real-world nonrandomized observational studies with greater numbers of patients but the admitted potential for selection bias and residual confounding, DES use was associated with reduced death and myocardial infarction. Both RCTs and observational studies demonstrated marked and comparable reductions in target vessel revascularization with DES compared with BMS. These data in aggregate suggest that DES are safe and efficacious in both on-label and off-label use but highlight differences between RCT and observational data comparing DES and BMS.

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.

Vascular closure devices: the second decade.

Vascular closure devices (VCDs) introduce a novel means for improving patient comfort and accelerating ambulation after invasive cardiovascular procedures performed via femoral arterial access. Vascular closure devices have provided simple, rapid, and reliable hemostasis in a variety of clinical settings. Despite more than a decade of development, however, VCD utilization has neither been routine in the U.S. nor around the world. Their limited adoption reflects concerns of higher costs for cardiac procedures and a lack of data confirming a significant reduction in vascular complications compared with manual compression. Recent data, however, suggest that VCD are improving, complication rates associated with their use may be decreasing, and their utilization may improve the process of care after femoral artery access. Challenges in the second decade of VCD experience will include performing definitive randomized trials, evaluating outcomes in higher-risk patients, and developing more ideal closure devices.

Vascular closure devices in patients treated with anticoagulation and IIb/IIIa receptor inhibitors during percutaneous revascularization.

OBJECTIVES The study assessed clinical outcomes of closure device use following percutaneous coronary revascularization using current standards of anticoagulation and antiplatelet therapy. BACKGROUND Evaluation of the outcomes of patients by use of vascular closure devices during coronary interventions employing current standards of anticoagulation and glycoprotein (GP) IIb/IIIa inhibitor therapy is limited. METHODS We evaluated outcomes of 4,525 consecutive patients who underwent percutaneous coronary intervention between July 1997 and April 2000. All patients received anticoagulation with heparin and GP IIb/IIIa inhibitor therapy with abciximab. The closure method was manual in 1,824 patients, Angioseal in 524 patients and Perclose in 2,177 patients. Procedural and hospital vascular outcomes were evaluated. RESULTS Closure device success was 97.1% Angioseal and 94.1% Perclose (p < 0.05). Minor vascular complications occurred in 1.8% of manual patients, 1.1% of Angioseal patients and 1.2% of Perclose patients (p = NS); major complications occurred in 1.3% of manual patients, 1.1% of Angioseal patients and 1.0% of Perclose patients (p = NS). Multivariate logistic regression identified only closure device failure as an independent predictor of a vascular complication. In patients with successful closure with a device, minor complications (0.8% vs. 1.8%, p < 0.05) and any complication (1.5% vs. 2.5%, p < 0.05) were reduced compared to manual compression. CONCLUSIONS Arterial closure following coronary interventions using anticoagulation and GP IIb/IIIa inhibitor therapy can be safely and effectively performed, with vascular complication rates similar to or lower than with manual pressure. Additionally, vascular complication rates using GP IIb/IIIa inhibitor therapy regardless of the method of arterial closure are equivalent to or lower than previously published rates of vascular complications.

Bleeding avoidance strategies. Consensus and controversy.

Bleeding complications after coronary intervention are associated with prolonged hospitalization, increased hospital costs, patient dissatisfaction, morbidity, and 1-year mortality. Bleeding avoidance strategies is a term incorporating multiple modalities that aim to reduce bleeding and vascular complications after cardiovascular catheterization. Recent improvements in the rates of bleeding complications after invasive cardiovascular procedures suggest that the clinical community has successfully embraced specific strategies and improved patient care in this area. There remains controversy regarding the efficacy, safety, and/or practicality of 3 key bleeding avoidance strategies for cardiac catheterization and coronary intervention: procedural (radial artery approach, safezone arteriotomy), pharmacological (multiple agents), and technological (vascular closure devices) approaches to improved access. In this paper, we address areas of consensus with respect to selected modalities in order to define the role of each strategy in current practice. Furthermore, we focus on areas of controversy for selected modalities in order to define key areas warranting cautious clinical approaches and the need for future randomized clinical trials in this area.

Simultaneous conductance catheter and dimension assessment of left ventricle volume in the intact animal.

We compared left ventricle (LV) volume (V) simultaneously measured using the conductance catheter (VM) with volume calculated from three LV dimensions (VD) determined ultrasonically from endocardial crystals. Seven adult mongrel dogs (20-30 kg) were anesthetized and instrumented to measure micromanometer LV pressure and V. Three pairs of crystals were placed orthogonally in subendocardial positions and a conductance catheter was placed in the LV retrograde across the aortic valve. Under steady-state conditions, over the range of a single cardiac cycle, the relation between VM and VD was well described by a straight line. There was an excellent correlation of conductance and dimension volumes with r equal to 0.97 +/- 0.04 and SEE 0.8 +/- 0.5 ml. The gain (1/alpha) and parallel conductance volume (alpha VC) were constant. At lower volumes obtained during bicaval occlusion, however, the relation between VM and VD was curvilinear. 1/alpha and alpha VC both decreased as LVV fell. Thus, determination of absolute volume using the conductance catheter depended on the conditions under which the data were obtained. Under steady-state conditions, alpha VC calculated by both the saline method (mean +/- SD, 50 +/- 15 ml) and by regression of VM and VD, (45 +/- 21 ml) were similar. Consequently, absolute LV end-diastolic volumes and end-systolic volumes by the conductance and dimension methods were similar (53 +/- 14 ml and 38 +/- 14 ml vs. 56 +/- 17 ml and 44 +/- 16 ml, respectively, p = NS). When volume decreased during bicaval occlusion, there was a progressively greater decrease in VM as compared with VD. The absolute slope (EES) of the end-systolic pressure-volume relation (ESPVR) was consistently higher by the dimension method, group average, 16.3 +/- 7.6, than by the catheter, 8.5 +/- 5.9, p less than 0.05. The direction and magnitude of the change in EES at different inotropic states (autonomic blockade; dobutamine), however, was similarly measured by both the conductance catheter and dimension method. We conclude that the gain and offset of the conductance catheter are relatively constant at steady state but vary when volume is reduced by caval occlusion. Thus, the conductance catheter accurately measures absolute volumes at steady state but can underestimate the slope and position of the ESPVR when it is determined by caval occlusion. The conductance catheter does, however, accurately measure the directions and magnitude of change in contractile state.

State-of-the-Art PaperVascular Closure Devices: The Second Decade

Vascular closure devices (VCDs) introduce a novel means for improving patient comfort and accelerating ambulation after invasive cardiovascular procedures performed via femoral arterial access. Vascular closure devices have provided simple, rapid, and reliable hemostasis in a variety of clinical settings. Despite more than a decade of development, however, VCD utilization has neither been routine in the U.S. nor around the world. Their limited adoption reflects concerns of higher costs for cardiac procedures and a lack of data confirming a significant reduction in vascular complications compared with manual compression. Recent data, however, suggest that VCD are improving, complication rates associated with their use may be decreasing, and their utilization may improve the process of care after femoral artery access. Challenges in the second decade of VCD experience will include performing definitive randomized trials, evaluating outcomes in higher-risk patients, and developing more ideal closure devices.

Incidence and predictors of coronary stent thrombosis: Evidence from an international collaborative meta-analysis including 30 studies, 221,066 patients, and 4276 thromboses

BACKGROUND Stent thrombosis remains among the most feared complications of percutaneous coronary intervention (PCI) with stenting. However, data on its incidence and predictors are sparse and conflicting. We thus aimed to perform a collaborative systematic review on incidence and predictors of stent thrombosis. METHODS PubMed was systematically searched for eligible studies from the drug-eluting stent (DES) era (1/2002-12/2010). Studies were selected if including ≥ 2000 patients undergoing stenting or reporting on ≥ 25 thromboses. Study features, patient characteristics, and incidence of stent thrombosis were abstracted and pooled, when appropriate, with random-effect methods (point estimate [95% confidence intervals]), and consistency of predictors was formally appraised. RESULTS A total of 30 studies were identified (221,066 patients, 4276 thromboses), with DES used in 87%. After a median of 22 months, definite, probable, or possible stent thrombosis had occurred in 2.4% (2.0%; 2.9%), with acute in 0.4% (0.2%; 0.6%), subacute in 1.1% (1.0%; 1.3%), late in 0.5% (0.4%; 0.6%), and very late in 0.6% (0.4%; 0.8%). Similar figures were computed for studies reporting only on DES. From a total of 47 candidate variables, definite/probable stent thrombosis was more commonly and consistently predicted by early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length, with acute coronary syndrome at admission, diabetes, smoking status, and bifurcation/ostial disease also proving frequent predictors, but less consistently. CONCLUSIONS Despite numerous possible risk factors, the most common and consistent predictors of stent thrombosis are early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length.

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).