Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (fantastic) study

BACKGROUND: Dual therapy with ticlopidine and aspirin has been shown to be as effective as or more effective than conventional anticoagulation in patients with an optimal result after implantation of intracoronary metallic stents. However, the safety and efficacy of antiplatelet therapy alone in an unselected population has not been evaluated. METHODS: Patients were randomized to conventional anticoagulation or to treatment with antiplatelet therapy alone. Indications for stenting were classified as elective (decided before the procedure) or unplanned (to salvage failed angioplasty or to optimize the results of balloon angioplasty). After stenting, patients received aspirin and either ticlopidine or conventional anticoagulation (heparin or oral anticoagulant). The primary end point was the occurrence of bleeding or peripheral vascular complications; secondary end points were cardiac events (death, infarction, or stent occlusion) and duration of hospitalization. RESULTS: In 13 centers, 236 patients were randomized to anticoagulation and 249 to antiplatelet therapy. Stenting was elective in 58% of patients and unplanned in 42%. Stent implantation was successfully achieved in 99% of patients. A primary end point occurred in 33 patients (13.5%) in the antiplatelet group and 48 patients (21%) in the anticoagulation group (odds ratio=0.6 [95% CI 0.36 to 0.98], P=0.03). Major cardiac-related events in electively stented patients were less common (odds ratio=0.23 [95% CI 0.05 to 0.91], P=0.01) in the antiplatelet group (3 of 123, 2.4%) than the anticoagulation group (11 of 111, 9.9%). Hospital stay was significantly shorter in the antiplatelet group (4.3+/-3.6 versus 6. 4+/-3.7 days, P=0.0001). CONCLUSIONS: Antiplatelet therapy after coronary stenting significantly reduced rates of bleeding and subacute stent occlusion compared with conventional anticoagulation.     

Introduction to coronary artery stents and their pharmacotherapeutic management

OBJECTIVE: To provide an introduction to coronary artery stents and their pharmacologic management, including anticoagulant therapy and newer antiplatelet regimens. DATA SOURCES: A MEDLINE and current journal search of relevant articles that evaluated coronary stent success rates and anticoagulation or antiplatelet regimens. STUDY SELECTION: Data from the use of primarily the Palmaz-Schatz stent were included. Studies using vitamin K antagonists that are not commercially available in the US were excluded unless they compared an antiplatelet regimen with anticoagulation using the international normalized ratio (INR). DATA SYNTHESIS: Limitations with percutaneous transluminal coronary angioplasty (PTCA), such as ischemic complications and restenosis, have led to the advent of intracoronary stenting. However, the placement of a stent within the coronary artery lumen is associated with a risk of thrombotic events. Despite current postprocedural anticoagulation and antiplatelet regimens, thrombosis occurs at rates ranging from 0.6% to 21%. When anticoagulation is deemed appropriate, it should be used for 1-2 months and the INR should be maintained between 2 and 3.5. Anticoagulation appears to have no effect on the development of restenosis, but has been shown to cause significant hemorrhagic events in 5-13.5% of patients. Newer data continue to define the subsets of patients who may be managed with antiplatelet agents alone. Combinations of aspirin and ticlopidine or aspirin alone may be used to manage patients who fulfill the following criteria: optimal stent placement, high-pressure inflation, and adequate coronary size. CONCLUSIONS: Coronary artery stenting is a novel approach for the management of coronary artery disease, but is associated with the complication of stent thrombosis. Anticoagulation reduces the risk of stent thrombosis, but is associated with bleeding risk. Selected patients may be successfully managed with antiplatelet agents only. More data are needed to better define the optimal antithrombotic regimen.     

Improved risk stratification in unstable angina: identification of patients at low risk for in-hospital cardiac events by admission echocardiography

BACKGROUND: Current protocols for risk stratification of patients with acute chest pain syndromes rely on clinical parameters and are oriented toward identification of patients at high risk for adverse cardiac events; however, this paradigm for risk stratification does not adequately address the observation that adverse cardiac events are relatively uncommon in this population. In an era of cost containment, consideration also should be given to identification of patients at low risk for adverse cardiac events, who may be safely discharged without expensive inpatient hospitalization. HYPOTHESIS: The purpose of this study was to develop echocardiographic predictors that identify unstable angina patients at low risk for adverse cardiac events and that discriminate between low- and high-risk patients. METHODS: The predictive accuracy of retrospectively determined echocardiographic predictors were compared in a population-based sample of 66 consecutive unstable angina patients undergoing echocardiography within 24 h of admission. RESULTS: Echocardiographic predictors of adverse events included wall motion score index > or = 0.2, ejection fraction < or = 40%, and mitral regurgitation severity > 2. One or more echocardiographic predictors of adverse events were present in 32 patients (48%). A composite echocardiographic predictor of adverse events was specific, had a high positive predictive value for the identification of high-risk patients, and discriminated between unstable angina patients at high and low risk for adverse cardiac events. CONCLUSION: Echocardiographic predictors of adverse events are specific and discriminate between unstable angina patients at high and low risk for adverse cardiac events.     

Management of patients with unstable angina in a general cardiology unit

AIMS: To review the clinical management of patients with unstable angina and to relate prospectively initial risk stratification, according to the Braunwald criteria, to subsequent cardiovascular events. METHODS: From February to April 1996 we performed a three month prospective review of all patients with a diagnosis of unstable angina admitted to the coronary care unit at Auckland Hospital. RESULTS: One hundred and four patients (61% male), with a mean age of 64 years, were classified as high (58%), intermediate (41%) or low risk (1%) for an adverse cardiac event. Twelve (12%) patients had a documented myocardial infarction, of whom 11 were in the high-risk group (p = 0.038). During hospitalisation there was one death. Twelve (12%) patients underwent inpatient exercise testing, five of whom proceeded to a coronary angiogram prior to hospital discharge. Twenty-two (21%) unstable patients underwent inpatient angiography without prior exercise testing. Twenty-one (20%) patients required revascularisation on the same admission: percutaneous coronary angioplasty (n = 14) or coronary artery bypass grafting (n = 7). Twelve of these 21 patients were in the high-risk group (p = 0.999, NS). CONCLUSION: Patients admitted with unstable angina had low inpatient mortality but a 12% rate of subsequent myocardial infarction. Braunwald low-risk unstable angina patients were not admitted to the coronary care unit. Braunwald high-risk patients were more likely to develop a subsequent myocardial infarction. Stratification of patients into intermediate or high-risk groups did not relate to initial medical management or subsequent revascularisation. Thus, while this method of risk stratification may predict cardiovascular events, it may be of limited clinical use in the New Zealand environment.     

Incremental prognostic value of adenosine stress myocardial perfusion single-photon emission computed tomography and impact on subsequent management in patients with or suspected of having myocardial ischemia

We examined 1,159 consecutive patients who underwent adenosine stress dual isotope single-photon emission computed tomography (SPECT) and had follow-up performed at a mean of 27.5 +/- 9.1 months (94% complete) for hard events (cardiac death and myocardial infarction) and referral to cardiac catheterization after nuclear testing. During follow-up, 120 hard events occurred (11.0% hard event rate; 72 cardiac deaths [6.7% cardiac death rate] and 57 myocardial infarctions [5.3% myocardial infarction rate]). Cox proportional hazards analysis revealed that nuclear testing added incremental value after adjusting for clinical and historical variables (global chi-square increased 13 to 98 for cardiac death as the end point, global chi-square increased 19 to 105 for hard events as the end point; p <0.0001 for both). Kaplan-Meier analysis demonstrated that after clinical risk stratification of the patient population, the results of nuclear testing were further able to significantly stratify both low- and intermediate- to high-risk patients. Patients with both normal and mildly abnormal scans were at low risk of cardiac death (<1% cardiac death per year of follow-up) and the risk of events increased significantly with worsening scan result. Multivariable analysis revealed that the only predictor of referral to catheterization was the extent and severity of reversible defect present on the scan. Referral rates to early catheterization were very low in patients with normal scans and increased significantly as a function of worsening scan results. In patients who underwent myocardial perfusion SPECT using adenosine stress, the results of nuclear testing yielded incremental prognostic information and clinically relevant risk stratification. Referring physicians predominantly utilized nuclear information when referring patients to catheterization after nuclear testing and do so at rates comparable with those after exercise SPECT despite the higher risk of events in patients undergoing pharmacologic stress.     

Restenosis rates in diabetic patients: a comparison of coronary stenting and balloon angioplasty in native coronary vessels

BACKGROUND: Diabetes is a major risk factor for restenosis after coronary balloon angioplasty. Recent studies have shown that coronary stenting significantly reduces restenosis compared with balloon angioplasty alone. However, limited information is available on the effect of coronary stenting in diabetic patients. METHODS AND RESULTS: We designed this study to analyze the effect of diabetes on restenosis in patients treated with either balloon angioplasty or coronary stenting who were enrolled in a 6-month angiographic follow-up program. Three hundred consecutive patients, 19% of whom were diabetics, who underwent coronary stent implantation during a single-vessel procedure on native coronary vessels and who had 6-month angiographic follow-up constituted the study group (stent group). Three hundred consecutive patients who underwent 6-month angiographic follow-up after single-vessel conventional balloon angioplasty served as control patients (balloon group). Preprocedural, postprocedural, and follow-up angiograms were analyzed with quantitative angiography. In the balloon group, the restenosis rate was almost twofold higher in diabetic than in nondiabetic patients (63% versus 36%; P=.0002) owing to both a greater late loss (0.79+/-0.70 versus 0.41+/-0.61 mm, respectively; P<.0001) and a higher rate of late vessel occlusion (14% versus 3%, respectively; P<.001). In the stent group, restenosis rates were similar in diabetics and nondiabetics (25% versus 27%, respectively). Furthermore, in the stent group, late loss (0.77+/-0.65 versus 0.79+/-0.57 mm, respectively) and the rate of late vessel occlusion (2% versus 1%, respectively) did not differ significantly between diabetic and nondiabetic patients. CONCLUSIONS: Although diabetics have increased rates of restenosis and late vessel occlusion after simple balloon angioplasty, they have the same improved outcome with coronary stenting that has been documented in nondiabetic patients.     

Thrombosis, antithrombotic agents, and the antithrombotic approach in cardiac disease

To develop a rational approach to antithrombotic therapy, in cardiac disease, a sound understanding is required (1) of the hemostatic processes leading to thrombosis, (2) of the various antithrombotic agents, and (3) of the relative risks of thrombosis and thromboembolism in the various cardiac disease entities. With the understanding of pathogenesis and risk of thrombus formation, a rational approach to the use of antiplatelet and anticoagulant agents can be formulated. Those at high risk of thrombus formation should generally receive a high degree of antithrombotics and, depending on the pathophysiology of the thrombus, may benefit from the concomitant use of antiplatelet and anticoagulant agents. Those with a medium risk of thrombus formation may benefit with the use of an antiplatelet agent alone or anticoagulants alone. Patients at low risk of thrombus formation should not receive antithrombotics. Such rational approach to antithrombotic therapy serves as the basis of this article.     

Isolated hemihyperplasia (hemihypertrophy): report of a prospective multicenter study of the incidence of neoplasia and review

The aim of the study was to determine whether or not dipyridamole thallium-201 single-photon emission computed tomography (201Tl-SPECT) has significant additive value for predicting perioperative cardiac events in patients with arteriosclerosis obliterans (ASO) undergoing vascular surgery. Routine preoperative 201Tl-SPECT was performed in 106 consecutive patients with ASO (age 68+/-8.9 years; 91 men and 15 women). The frequency of reversible defects in a clinical high-risk group (n=44) was significantly higher than in a low-risk group (n=62; 55% vs 24%, p<0.01). Perioperative cardiac events occurred in 9 patients, including 4 cardiac deaths, 1 non-fatal myocardial infarction, and 4 cases of unstable angina. Although clinical risk stratification was useful in predicting cardiac events (19% in the high-risk group vs 2% in the low-risk group, p<0.01), the positive predictive value was low. When considering a combination of 2 or more than 2 risk factors and a large reversible defect as a predictor, the positive predictive value and specificity increased from 19% to 47% and from 64% to 91%, respectively, whereas the sensitivity remained unchanged (89%). These results suggest that the addition of 201Tl-SPECT data to clinical risk-stratified patients with ASO allows better prediction of perioperative cardiac events.     

Superiority of nitrate-enhanced 201Tl over conventional redistribution 201Tl imaging for prognostic evaluation after myocardial infarction and thrombolysis

BACKGROUND: 201Tl imaging has been widely used for postinfarction risk stratification. However, thrombolytic therapy and aspirin have significantly changed outcome, and there are few nuclear imaging studies that assess prognosis in such patients. Furthermore, newer techniques of 201Tl imaging, such as reinjection and nitrate-enhanced rest 201Tl imaging, have been shown to improve the detection of viable but jeopardized myocardium. METHODS AND RESULTS: We studied 100 consecutive patients, who remained event free 6 weeks after myocardial infarction and thrombolysis. Patients underwent conventional exercise and 4-hour redistribution imaging, followed on a separate day by nitrate-enhanced rest 201Tl study. Planar images were reported semiquantitatively by two experienced observers blinded to clinical data. Redistribution and rest injection images were classified as demonstrating reversible ischemia if they showed improvement in uptake by at least two grades in at least two segments in comparison with the initial exercise scintigram. Patients were followed up for 8 to 32 months (mean, 21 months); during this period, 37 patients had first cardiac events. Reversible ischemia was present in 29 patients on redistribution, of whom 14 (48%) had events; of 71 without reversible defects, 23 (32%) had events (hazard ratio, 1.5; 95% CI, 0.8 to 3.0; P=NS). Nitrate-enhanced rest 201Tl imaging detected reversible defects in 68 patients, of whom 33 (49%) had events, whereas of 32 without reversible defects, only 4 (13%) had subsequent cardiac events (hazard ratio, 8.1; 95% CI, 2.7 to 23.8; P<.001). CONCLUSIONS: Thus, after myocardial infarction and thrombolysis, even "stable" patients have a high (68%) incidence of viable but jeopardized myocardium, causing a high event rate. Those identified to be at high risk by perfusion imaging may benefit from early intervention.     

Influence of various antithrombotic therapy methods on the incidence of subacute coronary stent occlusions, hemorrhagic complications and length of hospitalization

BACKGROUND: The clinical benefit of coronary stenting is reduced by the risk of thrombotic stent occlusion as well as hemorrhagic complications of intensive antithrombotic therapy. We compared the influence of different antithrombotic therapies on the incidence of post-interventional complications and in-hospital stay duration. METHODS: After successful placement of a coronary stent, 334 consecutive patients were given different antithrombotic treatments in addition to aspirin 100 mg/d indefinitely: (1) phenprocoumon for 3 months (n = 47), (2) low molecular weight heparin 2 x 100 U/kg/d s.c. for 4 weeks (n = 90), (3) ticlopidine 2 x 250 mg/d and low molecular weight heparin 2 x 100 U/kg/d s.c. for 4 weeks (n = 72) and (4) ticlopidine 2 x 250 mg/d for 4 weeks (n = 125). RESULTS: Major events were subacute stent thrombosis in 17 patients (5%), and severe hemorrhagic complication in 20 patients (5.9%). The incidence of subacute stent thrombosis in groups 1 to 4 was 10.6%, 11%, 1.4% and 0.8% respectively. The use of ticlopidine was associated with a significant lowering of stent occlusions in univariate and multivariate analysis (p = 0.0013). Additional uni- and multivariate predictors were stent placement as a "bail-out" procedure (p = 0.033) and in patients with acute coronary syndrome (p = 0.049). Anticoagulant therapy was associated with a higher incidence of severe hemorrhagic complications (p < 0.01) and a prolonged in-hospital stay (p = 0.01). CONCLUSIONS: These results confirm that anti-thrombotic therapy with aspirin and ticlopidine combines low rates of subacute stent occlusion and hemorrhagic complications. Treatment with phenprocoumon and low molecular weight heparin does not improve the rate of subacute stent occlusion but increases hemorrhagic complications. Very low rates of stent occlusion permit short in-hospital stays with concomitant reduction in cost.     

Dipyridamole stress echocardiography for risk stratification in hypertensive patients with chest pain

BACKGROUND: The noninvasive prognostic assessment of coronary artery disease (CAD) in hypertensive patients represents an unresolved task to date. In this study, we investigated the value of dipyridamole stress echocardiography in risk stratification of hypertensive patients with chest pain and unknown CAD. METHODS AND RESULTS: Dipyridamole stress echocardiography was performed in 257 hypertensives (110 men; age, 63+/-9 years) complaining of chest pain and without a history of CAD. No major complications occurred. Four tests were interrupted prematurely because of side effects, with 98. 4% feasibility of test. A positive echocardiographic response was found in 72 patients (27 during the low-dose [0.56 mg/kg]). During the follow-up (32+/-18 months), 27 cardiac events occurred: 3 deaths, 8 infarctions, and 16 cases of unstable angina. Moreover, 27 patients underwent coronary revascularization. At multivariate analysis, the positive echocardiographic result (OR, 5.5; 95% CI, 1.4 to 16.6) was the only predictor of hard cardiac events (death, infarction). Considering spontaneous cardiac events (death, infarction, and unstable angina) as end points, the positive echocardiographic result (OR, 4.2; 95% CI, 1.8 to 9.6) and family history of CAD (OR, 4.2; 95% CI, 1.5 to 6. 9) were independently associated with prognosis. The 3-year survival rates for the negative and the positive populations were, respectively, 97% and 87% (P=0.0019) considering hard cardiac events and 96% and 74% (P=0.0000) considering spontaneous cardiac events. CONCLUSIONS: Dipyridamole stress echocardiography is safe, highly feasible, and effective in risk stratification of hypertensives with chest pain and unknown CAD. At present, it represents an attractive option for prognostic assessment of this clinically defined population.     

Reduction of in-hospital complications after elective percutaneous transluminal coronary angioplasty using a combined pretreatment with ticlopidine and aspirin

OBJECTIVES: In a retrospective study the effect of a combined pretreatment using ticlopidine and aspirin (ASA) in patients undergoing elective PTCA procedures was investigated with respect to in-hospital complications of PTCA and with respect to the efficacy in avoiding a subacute stent thrombosis in case of stent implantation. The systematically performed pretreatment with ticlopidine and ASA takes the delayed begin of full antiplatelet effect of ticlopidine into account. METHODS: 1108 consecutive patients (group 1) underwent elective PTCA without pretreatment with ticlopidine. In case of stent implantation oral anticoagulation was initiated in this group. In 758 consecutive patients (group 2) with elective PTCA, a combined regimen with ticlopidine and ASA was initiated at least 24 h prior to PTCA and was continued in case of stent implantation. The rate of procedural success, necessary reinterventions, cardiac events (myocardial infarction, death) and complications as well as the rate of subacute stent thrombosis in the subgroups with stent implantation were evaluated. RESULTS: The number of patients without in-hospital cardiac complications (myocardial infarction, coronary artery bypass surgery, death) and without re-PTCA interventions was 92.8% in group 1 and 96.3% in group 2 (p < 0.005). Especially the rate of necessary reinterventions was significantly reduced in group 2 compared with group 1 (5.3% vs. 2.4%, p < 0.001). Cardiac events were reduced in group 2 (myocardial infarction: 2.0% vs. 1.1%, coronary artery bypass graft: 0.8% vs. 0.5%, exitus: 0.5% vs. 0%), the incidence of bleeding complications was similar in both groups (2.5% vs. 2.4%). The combined pretreatment with ticlopidine and ASA with a stent implantation rate of 16.4% in group 2 was effective to avoid a subacute stent thrombosis (1.6%, independent of the indication to stent implantation). One patient of 758 in group 2 had allergic reactions to ticlopidine. CONCLUSIONS: The "prophylactic" pretreatment with ticlopidine and ASA in combination with a higher rate of stent implantation reduces necessary reinterventions and cardiac events after PTCA and is effective to avoid subacute stent thrombosis without increase of complications, especially bleeding complications. Thus, this pretreatment can be proposed even in patients scheduled for elective PTCA without planned stent implantation to reduce the interval between a necessary unforeseen stent implantation and the full treatment effects of ticlopidine.     

Antithrombotic therapy after coronary stent placement

Subacute stent thrombosis and hemorrhagic complications due to intensive anticoagulant therapy limit the clinical benefit of coronary stenting. Antithrombotic therapy after coronary stent placement has not been standardized yet. From January 1994 to December 1995 a total of 338 Palmaz-Schatz stents were implanted in 285 patients. Procedural success rate was 98.8%. In the initial period, after stent placement, patients were treated with acetylsalicylic acid (ASA) and warfarin (135 patients, Group A), while subsequently, according to the results of other studies, patients were treated with ASA plus ticlopidine (146 patients, Group B). Two hours after sheath removal, Group A patients were treated with intravenous heparin until therapeutic INR (2.5-3.5) was reached; warfarin was stopped 3 months later. In Group B patients 2 hours after sheath removal a treatment with subcutaneous heparin 25,000 IU/die plus ticlopidine 500 mg/die was started. Subcutaneous heparin was maintained until hospital discharge, ticlopidine was stopped after 1 month and ASA was maintained indefinitely. There were no significant differences in baseline characteristics between the two groups. Most patients had unstable angina and in the majority of cases the stent was implanted due to intimal dissection after balloon dilation. Eleven patients had subacute thrombosis of the stent (3.9%): 9 patients were in Group A (6%) and 2 patients were in Group B (1.3%; p = 0.04). Seven patients (6 in Group A, 1 in Group B) were treated with emergency coronary angioplasty and 3 (2 in Group A, 1 in Group B) with coronary bypass; nevertheless 7 patients (6 in Group A, 1 in Group B) had an acute myocardial infarction. Eight patients (6 in Group A, 2 in Group B) had major bleeding due to a large groin hematoma requiring blood transfusion or vascular surgery. In conclusion, after coronary stenting antithrombotic therapy with ASA plus ticlopidine, as compared with anticoagulant therapy, reduces the incidence of both cardiac events and hemorrhagic complications.     

Heparin-coated Palmaz-Schatz stents in human coronary arteries. Early outcome of the Benestent-II Pilot Study

BACKGROUND: The purpose of the Benestent-II Pilot Study was to evaluate the safety of delaying and eliminating anticoagulant therapy in patients receiving a heparin-coated stent in conjunction with antiplatelet drugs. METHODS AND RESULTS: The study consisted of three initial phases (I, II, III) during which resumption of heparin therapy after sheath removal was progressively deferred by 6, 12, and 36 hours. In phase IV, coumadin and heparin were replaced by 250 mg ticlopidine and 100 mg aspirin. Of the 207 patients with stable angina pectoris and a de novo lesion in whom heparin-coated stent implantation was attempted, implantation was successful in 202 patients (98%). Stent thrombosis did not occur during all four phases, and the overall clinical success rate at discharge was 99%. Bleeding complications requiring blood transfusion or surgery fell from 7.9% in phase I to 5.9%, 4%, and 0% in the three following phases. Hospital stay was 7.4, 6.1, 7.2, and 3.1 days for the consecutive phases. The restenosis rate for the combined four phases was 13% (15% in phase I, 20% in phase II, 11% in phase III, and 6% in phase IV). The overall rate of reintervention for the four phases was 8.9%. At 6 months, 84%, 75%, 94%, and 92% of the patients of phases I to IV, respectively, were event free. For the four phases, the event-free rate was 86%, which compares favorably with the rate observed in the Benestent-I study (80%; relative risk, 0.68 [0.45 to 1.04]). CONCLUSIONS: The implantation of stents coated with polyamine and end-point-attached heparin in stable patients with one significant de novo coronary lesion is well tolerated, is associated with no (sub)acute stent thrombosis, and results in a favorable event-free survival after 6 months.     

Indications for carotid endarterectomy in patients with symptoms: when, where?

Carotid endarterectomy (CEA) is one of the most commonly used surgical methods in the treatment of cerebral stroke with both therapeutic and also prophylactic implications. CEA has been used in surgical practice for 40 years. At the beginning it was very popular and was widely used. Later, the opposite extreme was reached, and its therapeutic efficacy was denied unjustifiably. However, at the beginning of the ninetieth three large controlled studies were completed (North American Symptomatic Carotid Endarterectomy Trial, European Carotid Surgery Trial and Veterans Administrations Symptomatic Trial) and the results of these trials were the basis for establishing the solid criteria for the surgical procedure in some groups of symptomatic patients with stenosis of the internal carotid artery. Thus, CEA was in again. In accordance with the attitudes of the American Association Ad Hoc Committee (1995), evidenced indications for CEA in patients with symptomatic stenosis of the internal carotid artery (in the group with surgical risk less than 6%) include (a) single or recurrent episodes of TIA in the last 6 months, "crescendo" TIA combined with carotid stenosis > 70% with or without plaque ulceration, with or without antiplatelet therapy, and (b) mild stroke in last 6 months with carotid stenosis > 70% with or without plaque ulceration, with or without antiplatelet therapy. The authors report their experience and results of a six-month pilot study of 301 patients, of whom 248 were operated on for symptomatic carotid stenosis with low combined perioperative morbidity and mortality (0.6%). Also, indications for surgical reconstruction of carotid and coronary arteries in patients with marked signs of atherosclerosis in both arterial systems are discussed.     

Bleeding complications with new antithrombotics used in ischaemic heart disease

Despite adjunctive therapy with heparin and aspirin, patients undergoing percutaneous transluminal coronary angioplasty (PTCA) continue to be at risk of abrupt vessel closure and acute ischaemic events. In an attempt to overcome the limitations of traditional antithrombotics, more potent agents have been developed, including direct thrombin inhibitors (e.g., hirudin and hirulog) and new antiplatelet agents [e.g., the glycoprotein IIb/IIIa receptor inhibitor c7E3 Fab (ReoProTM)]. Initial phase-III trials of hirudin in patients with acute coronary syndromes identified an excess incidence of major bleeding complications. Some of these trials have been recommenced using lower doses. Reports on phase-III trials of hirulog should be forthcoming soon. Of the new agents, the chimeric monoclonal antibody fragment c7E3 Fab has the most extensive available data. In the phase-III evaluation of 7E3 for the Prevention of Ischemic Complications trial, the administration of a c7E3 Fab bolus plus c7E3 Fab infusion reduced the rate of major ischaemic events by 35% at 30 days (p = 0.008) in patients undergoing high-risk PTCA. Major bleeding episodes occurred more frequently with this regimen than with placebo, although rates of intracranial haemorrhage or surgery for bleeding did not differ between groups. The findings suggest that the risk of bleeding complications might be reduced, without compromising efficacy, by administering heparin on a weight-adjusted basis in patients treated with c7E3 Fab.     

Stenting for ischemic heart disease

This article examines current indications to intracoronary stenting for percutaneous cardiac revascularization. The data sources are a review of the published English literature, with focus on clinical and randomized trails of coronary artery stenting. Stents reduce the need for emergency bypass surgery in the setting of acute or threatened vessel closure after percutaneous transluminal coronary angioplasty (PTCA). In selected cases, when deployed electively in large native vessels with focal stenosis, clinical and angiographic recurrence are significantly reduced. Preliminary studies have also suggested a potential role in the treatment of saphenous vein graft lesions and restenotic lesions, and in improving on suboptimal results in lesions refractory to balloon dilatation. To prevent stent thrombosis, adjunctive antiplatelet therapy has been shown to be more efficacious than anticoagulation, and optimal stent apposition to the vessel wall appears to be critical. A recent exponential increase in the use of coronary stents has revolutionized the contemporary practice of interventional cardiology. Although technical factors and feasibility have been well refined and shown, evidence-based practice is lacking for many patient subsets.     

Stent placement compared with balloon angioplasty for obstructed coronary bypass grafts. Saphenous Vein De Novo Trial Investigators

BACKGROUND: Treatment of stenosis in saphenous-vein grafts after coronary-artery bypass surgery is a difficult challenge. The purpose of this study was to compare the effects of stent placement with those of balloon angioplasty on clinical and angiographic outcomes in patients with obstructive disease of saphenous-vein grafts. METHODS: A total of 220 patients with new lesions in aortocoronary-venous bypass grafts were randomly assigned to placement of Palmaz-Schatz stents or standard balloon angioplasty. Coronary angiography was performed during the index procedure and six months later. RESULTS: As compared with the patients assigned to angioplasty, those assigned to stenting had a higher rate of procedural efficacy, defined as a reduction in stenosis to less than 50 percent of the vessel diameter without a major cardiac complication (92 percent vs. 69 percent, P<0.001), but they had more frequent hemorrhagic complications (17 percent vs. 5 percent, P<0.01). Patients in the stent group had a larger mean (+/-SD) increase in luminal diameter immediately after the procedure (1.92+/-0.30 mm, as compared with 1.21+/-0.37 mm in the angioplasty group; P<0.001) and a greater mean net gain in luminal diameter at six months (0.85+/-0.96 vs. 0.54+/-0.91 mm, P=0.002). Restenosis occurred in 37 percent of the patients in the stent group and in 46 percent of the patients in the angioplasty group (P=0.24). The outcome in terms of freedom from death, myocardial infarction, repeated bypass surgery, or revascularization of the target lesion was significantly better in the stent group (73 percent vs. 58 percent, P = 0.03). CONCLUSIONS: As compared with balloon angioplasty, stenting of selected venous bypass-graft lesions resulted in superior procedural outcomes, a larger gain in luminal diameter, and a reduction in major cardiac events. However, there was no significant benefit in the rate of angiographic restenosis, which was the primary end point of the study.     

The use of empiric clinical data in the evaluation of practice guidelines for unstable angina

OBJECTIVE: To determine the applicability to emergency department (ED) clinical practice of a nationally disseminated practice guideline on the disposition of patients with a diagnosis of unstable angina, and to determine the potential impact of the guideline on hospital admissions and demand for intensive care beds. DESIGN: Application of guideline criteria for ED disposition decisions to a validation sample derived from a prospective clinical trial. SETTING: Five hospitals, including 2 urban general teaching hospitals, 2 urban tertiary care university hospitals, and 1 suburban university-affiliated community hospital. PATIENTS: A consecutive sample of 457 patients who presented with symptoms suggestive of acute cardiac ischemia and who had "unstable angina" or "rule out unstable angina" diagnosed by ED physicians. Greater than 90% of eligible patients were enrolled in the clinical trial; follow-up data sufficient for assignment of a definitive diagnosis were obtained for 99% of subjects. MAIN OUTCOME MEASURES: Acute myocardial infarction and unstable angina, based on blind review of initial and follow-up clinical data, including cardiac enzyme levels and electrocardiograms. After completion of the trial, without knowledge of final diagnosis or outcome, the investigators classified patients into risk groups specified by the unstable angina guideline. RESULTS: Of subjects with an ED diagnosis of unstable angina, only 6% (n=28) met the guideline's criteria corresponding to low risk for adverse events and were therefore suitable for discharge directly to home. Fifty-four percent (n=247) met the intermediate-risk criteria; 40% (n=182) met the high-risk criteria and were identified as requiring admission to an intensive care unit. Actual ED disposition differed from guideline recommendations in 2 major areas: only 4% (1/28) of low-risk patients were discharged to home with outpatient follow-up, and only 40% (72/182) of high-risk patients were admitted to an intensive care unit. CONCLUSIONS: Although the guideline was intended to reduce hospitalization by identifying a low-risk group, the small size of this group among ED patients suggests that little reduction in hospitalization can be expected. Indeed, the guideline may increase demand for the limited number of intensive care beds to accommodate patients with unstable angina considered high-risk but currently placed elsewhere. These results emphasize the need to use empiric data from target clinical settings to assess the likely actual impact of guidelines on clinical care prior to national dissemination.     

Care of the patient and management of complications after percutaneous coronary artery interventions

Certain aspects of patient management are common with conventional balloon angioplasty and newer coronary artery interventions. These aspects include the evaluation of chest pain or treatment of acute vessel closure shortly after the intervention, management of the vascular access site (especially if complications occur), prevention and treatment of contrast-induced renal dysfunction, and the use of anticoagulant or antiplatelet agents after the procedure. However, some aspects of management vary among techniques. Several different drug therapies are indicated after these procedures, but pharmacologic therapy for restenosis has been largely unsuccessful. Placement of an intracoronary stent decreases the frequency of restenosis and subsequent revascularization procedures, and functional testing may be of value in some patients after coronary artery interventions. It is important for the specialist in internal medicine to have a firm working knowledge of the various aspects of care that are required because their role in management is increasing.