A randomized, placebo-controlled trial of enoxaparin after high-risk coronary stenting: the ATLAST trial.

OBJECTIVES: We performed a multicenter, double-blind placebo-controlled trial to examine the efficacy and safety of enoxaparin in patients at high risk for stent thrombosis (ST). BACKGROUND: The optimal antithrombotic regimen for such patients is unknown. METHODS: We randomized 1,102 patients with clinical, angiographic or ultrasonographic features associated with an increased risk of ST to receive either twice-daily injections of weight-adjusted enoxaparin or placebo for 14 days after stenting. All patients received aspirin and ticlopidine. The primary end point was a 30-day composite end point of death, myocardial infarction (MI) or urgent revascularization. RESULTS: The target enrollment for the study was 2,000 patients. However, the trial was terminated prematurely at 1,102 patients after interim analysis revealed an unexpectedly low event rate. The primary outcome occurred in 1.8% enoxaparin-treated patients versus 2.7% treated with placebo (odds ratio [OR] 0.66; 95% confidence interval [CI] 0.29 to 1.5, p = 0.30); for death or MI the rates were 0.9% vs. 2.2%, respectively (OR 0.41, 95% CI 0.14 to 1.2, p =0.13); and for MI, 0.4% vs. 1.6%, respectively (OR 0.22, 95% CI 0.05 to 0.99, p = 0.04). The groups had comparable rates of major bleeding (3.3% for enoxaparin, 1.6% for placebo, p =0.08), but minor nuisance bleeding was increased with enoxaparin (25% vs. 5.1%, p < 0.001). CONCLUSIONS: The clinical outcomes of patients at increased risk of ST are more favorable than previously reported, rendering routine oral antiplatelet therapy adequate for most. However, given its relative safety and potential to reduce the risk of subsequent infarction, a 14-day course of enoxaparin may be considered for carefully selected patients.

Contemporary outcome trends in the elderly undergoing percutaneous coronary interventions: results in 7,472 octogenarians. National Cardiovascular Network Collaboration.

OBJECTIVES: We sought to define the risks facing octogenarians undergoing contemporary percutaneous coronary interventions (PCIs). BACKGROUND: The procedural risks of PCI for octogenarians have not been well established. METHODS: We compared the clinical characteristics and in-hospital outcomes of 7,472 octogenarians (mean age 83 years) with those of 102,236 younger patients (mean age 62 years) who underwent PCI at 22 National Cardiovascular Network (NCN) hospitals from 1994 through 1997. RESULTS: Octogenarians had more comorbidities, more extensive coronary disease and a two- to fourfold increased risk of complications, including death (3.8% vs. 1.1%), Qwave myocardial infarction (1.9% vs. 1.3%), stroke (0.58% vs. 0.23%), renal failure (3.2% vs. 1.0%) and vascular complications (6.7% vs. 3.3%) (p < 0.001 for all comparisons). Independent predictors of procedural mortality in octogenarians included shock (odds ratio [OR] 5.4, 95% confidence interval [CI] 3.3 to 8.8), acute myocardial infarction (OR 3.2, 95% CI 2.3 to 4.4), left ventricular ejection fraction (LVEF) <35% (OR 2.9, 95% CI 2.1 to 3.9), renal insufficiency (OR 2.8, 95% CI 2.0 to 3.8), first PCI (OR 2.3, 95% CI 1.7 to 3.3), age >85 years (OR 2.1, 95% CI 1.5 to 2.7) and diabetes mellitus (OR 1.5, 95% CI 1.1 to 2.0). For elective procedures, octogenarian mortality varied nearly 10-fold, and was strongly influenced by comorbidities (0.79% mortality with no risk factors vs. 7.2% with renal insufficiency or LVEF <35%). Despite similar case-mix, PCI outcomes in octogenarians improved significantly over the four years of observation (OR of 0.61 for death/myocardial infarction/stroke in 1997 vs. 1994; 95% CI 0.45 to 0.85). CONCLUSIONS: Risks to octogenarians undergoing PCI are two- to fourfold higher than those of younger patients, strongly influenced by comorbidities, and have decreased in the stent era.

A comparison of ionic versus nonionic contrast medium during primary percutaneous transluminal coronary angioplasty for acute myocardial infarction (GUSTO IIb). Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes.

The clinical impact of contrast medium selection during primary percutaneous transluminal coronary angioplasty for acute myocardial infarction (AMI) has not been studied. We compared the clinical outcomes of patients who received ionic versus nonionic low osmolar contrast medium in the setting of primary percutaneous transluminal coronary angioplasty for AMI in the second Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) trial. Univariable and multivariable analyses were performed to assess the relation between contrast medium selection and clinical outcome (death, reinfarction, or refractory ischemia) at 30 days. Although baseline clinical and angiographic characteristics were generally similar between the 2 groups, patients who received ionic, low osmolar contrast were less likely to have been enrolled at a US site (23% vs 43%, p = 0.001) and less likely to have occlusion of the left anterior descending coronary artery (34% vs 47%, p = 0.03) or a history of prior AMI (8% vs 16%, p = 0.02). The triple composite end point of death, reinfarction, or refractory ischemia occurred less frequently in the ionic group, both in the hospital (4.4% vs 11%, p = 0.018) and at 30 days (5.5% vs 11%, p = 0.044). Although the trend favoring ionic contrast persisted, the differences were no longer statistically significant after adjustment for imbalances in baseline characteristics using a risk model developed from the study sample (n = 454, adjusted odds ratio for ionic contrast 0.48 [0.22 to 1.02], p = 0.055), and using a model developed from the entire GUSTO IIb study cohort (n = 12,142, adjusted odds ratio for ionic contrast 0.50 [0.23 to 1.06], p = 0.072). The results of this observational study warrant further elucidation by a randomized study design in this setting.

A comparison of U.S. and Canadian cardiac catheterization practices in detecting severe coronary artery disease after myocardial infarction: efficiency, yield and long-term implications.

OBJECTIVES: We sought to compare U.S. and Canada's post-myocardial infarction (MI) cardiac catheterization practices in the detection of severe coronary artery disease (CAD). BACKGROUND: Little is known about the efficiency with which the aggressive post-MI catheterization strategy observed in the U.S. detects severe CAD compared with the more conservative strategy observed in Canada. METHODS: From the U.S. and Canadian patients who had participated in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries trial (n = 22,280, 11.5% Canadian), we examined the frequency of in-hospital cardiac catheterization, the prevalence of severe CAD observed at catheterization (diagnostic efficiency) and the total number of MI patients with severe CAD identified (diagnostic yield). RESULTS: The rate of catheterization in the U.S. was more than 2.5 times that in Canada (71% vs. 27%, respectively, p < 0.001). With identical prevalences of severe CAD at catheterization (17%) in the two countries, the higher frequency of catheterization in the U.S. resulted in the identification of more than two and a half times as many cases of severe CAD compared with Canada (12 severe CAD cases identified per 100 post-MI patients in the U.S., vs. 4.6 per 100 in Canada). If considered in isolation, we estimated that these differences in severe disease detection might effect a small long-term survival advantage in favor of the U.S. strategy (estimated 5.0 lives saved per 1,000 MI patients). CONCLUSIONS: Canada's more restrictive post-MI cardiac catheterization strategy is no more efficient in identifying severe CAD than the aggressive U.S. strategy, and may fail to identify a substantial number of post-MI patients with high risk coronary anatomy. The long-term impact of these differences in practice patterns requires further evaluation.

The challenge of health care delivery to the elderly patient with cardiovascular disease. Demographic, epidemiologic, fiscal, and health policy implications.

Old age as our society is experiencing it is a new phenomenon. Never before in history have societies of developed countries enjoyed such longevity of life. In the next several decades the United States will face an unparalleled increase in the absolute number of elderly persons in our population. How will health care professionals, policy-makers, and society in general face the mammoth task of providing quality cardiovascular care for the elderly in an environment of limited financial resources? This article discusses the demographic, fiscal, and health policy implications of our aging society with particular emphasis on existing and anticipated impediments to the delivery of cardiovascular care to this rapidly expanding segment of our population.

The extracellular matrix in balloon arterial injury: a novel target for restenosis prevention.

The role of the extracellular matrix (ECM) in the pathobiology of restenosis has not been fully appreciated. Recent discoveries have shown the ECM to be a complex, heterogeneous structure whose components are dynamically altered in response to vascular injury. This report reviews the structure and function of vascular ECM and the importance of the matrix in modulating the vascular response to arterial injury such as balloon angioplasty and atherosclerosis.

Cardiac metastasis from primary cervical squamous cell carcinoma: three case reports and a review of the literature.

Clinically evident cardiac metastases from malignant neoplasms are uncommon, occurring most commonly in association with lung and breast carcinoma, lymphoma, leukemia and melanoma. The vast majority, over 90%, present with pericardial involvement. Squamous cell carcinomas of the cervix rarely produce cardiac metastases, with endomyocardia metastases being particularly rare. Three patients are reported who presented with primary squamous cell carcinoma of the cervix and developed this pattern of metastasis, one of whom was diagnosed at endomyocardial biopsy and the other two at autopsy. The paucity of such cases in the literature emphasizes the uniqueness of this phenomenon.

In vivo collagen turnover following experimental balloon angioplasty injury and the role of matrix metalloproteinases.

Extracellular matrix formation is the major component of the restenosis lesion that develops after balloon angioplasty. Although ex vivo studies have shown that the synthesis of collagen is stimulated early after balloon angioplasty, there is a delay in accumulation in the vessel wall. The objectives of this study were to assess collagen turnover and its possible regulation by matrix metalloproteinases (MMPs) in a double-injury iliac artery rabbit model of restenosis. Rabbits were killed at four time points (immediately and at 1, 4, and 12 weeks) after balloon angioplasty. In vivo collagen synthesis and collagen degradation were measured after a 24-hour incubation with [14C]proline. Arterial extracts were also run on gelatin zymograms to determine MMP (gelatinase) activity. Collagen turnover studies were repeated in a group of 1-week postangioplasty rabbits that were treated with daily subcutaneous injections of either a nonspecific MMP inhibitor, GM6001 (100 mg/kg per day), or placebo. Collagen synthesis and degradation showed similar temporal profiles, with significant increases in the balloon-injured iliac arteries compared with control nondilated contralateral iliac arteries immediately after angioplasty and at 1 and 4 weeks. Peak collagen synthesis and degradation occurred at 1 week and were increased (approximately four and three times control values, respectively). Gelatin zymography was consistent with the biochemical data by showing an increase of a 72-kD gelatinase (MMP-2) in the balloon-injured side immediately after the second injury, peaking at 1 week, and still detectable at 4 and 12 weeks (although at lower levels). In balloon-injured arteries, the MMP inhibitor reduced both collagen synthesis and degradation. Overall, at 1 week after balloon angioplasty, GM6001 resulted in a 33% reduction in collagen content in balloon-injured arteries compared with placebo (750 +/- 143 to 500 +/- 78 micrograms hydroxyproline per segment, P < .004), which was associated with a nonsignificant 25% reduction in intimal area. Our data suggest that degradation of newly synthesized collagen is an important mechanism regulating collagen accumulation and that MMPs have an integral role in collagen turnover after balloon angioplasty.

Early and late quantitative angiographic results of vein graft lesions treated by excimer laser with adjunctive balloon angioplasty.

BACKGROUND: Percutaneous excimer laser coronary angioplasty (PELCA) has been approved for treatment of diseased saphenous vein bypass grafts. However, detailed and complete quantitative angiographic analysis of immediate procedural and late follow-up results has not been performed. METHODS AND RESULTS: PELCA using the CVX-300 excimer laser system was performed in 125 bypass lesions (mean graft age, 96 +/- 53 months; range, 2 to 240 months) in 106 consecutive patients at eight centers. Quantitative analyses of the procedural and follow-up angiograms were done with the Cardiac Measurement System. Stand-alone PELCA was done in 21 lesions (17%). Lesions were located at the ostium (20%), body (67%), or distal anastomosis (13%). The graft reference diameter was 3.26 +/- 0.79 mm (mean +/- SD). Minimal lumen diameter increased from 1.09 +/- 0.52 mm before treatment to 1.61 +/- 0.69 mm after laser and 2.18 +/- 0.63 mm after adjunctive balloon dilation (P < .001) but had declined at follow-up to 1.40 +/- 1.17 mm. Dissections were evident in 45% of lesions after laser treatment (types A and B, 27%; types C through F, 18%), including 7% occlusions. Angiographic success (< or = 50% diameter stenosis [% DS]) was 54% after laser and 91% after adjunctive PTCA, with an overall clinical success rate of 89%. In-hospital complications were death, 0.9%; myocardial infarction (Q-wave and non-Q-wave), 4.5%; and bypass surgery, 0.9%. Independent predictors of % DS after laser were reference diameter, lesion length, and minimal lumen diameter before laser. At angiographic follow-up in 83% of eligible patients, the restenosis rate per lesion (DS > 50%) was 52%, including 23 occlusions (24%). The only independent predictor of increased % DS at follow-up was lesion symmetry. Logistic regression indicated that smaller reference diameter was an independent predictor of late occlusion. Overall 1-year mortality was 8.6%. Actuarial event-free survival (freedom from death, myocardial infarction, bypass surgery, or target vessel percutaneous transluminal coronary angioplasty) was 48.2% at 1 year. CONCLUSIONS: Excimer laser angioplasty with adjunctive balloon angioplasty can be safely and successfully performed in diseased, old saphenous vein bypass graft lesions considered at high risk for reintervention. The extent of laser ablation remains limited by the diameter and effectiveness of the catheters. Late restenosis and, in particular, total occlusion mitigate the early benefits of the procedure. Other approaches such as the routine use of additional anticoagulation (eg, warfarin) should be considered to reduce the risk of late occlusions and restenosis after laser angioplasty of bypass grafts.

Chaparral-induced hepatic injury.

Two patients with hepatic injury after ingestion of chaparral leaf are presented. The first patient, a 71-yr-old man, developed biopsy-proven hepatitis 3 months after ingesting chaparral leaf daily. His illness resolved with discontinuation of the herb and later recurred with rechallenge. The second patient is a 42-yr-old woman who developed hepatitis 2 months after chaparral leaf ingestion and recovered completely after discontinuation of the compound. Both patients have remained well with abstinence from chaparral. These reports provide evidence of the hepatotoxicity of this herb and stress the need for awareness of the potential harm from such nonprescription remedies.