The optimal management of patients on oral anticoagulation undergoing coronary artery stenting. The 10th Anniversary Overview.

Even 10 years after the first appearance in the literature of articles reporting on the management of patients on oral anticoagulation (OAC) undergoing percutaneous coronary intervention with stent (PCI-S), this issue is still controversial. Nonetheless, some guidance for the everyday management of this patient subset, accounting for about 5-8 % of all patients referred for PCI-S, has been developed. In general, a period of triple therapy (TT) of OAC, with either vitamin K-antagonists (VKA) or non-vitamin K-antagonist oral anticoagulants (NOAC), aspirin, and clopidogrel is warranted, followed by the combination of OAC, and a single antiplatelet agent for up to 12 months, and then OAC alone. The duration of the initial period of TT is dependent on the individual risk of thromboembolism, and bleeding, as well as the clinical context in which PCI-S is performed (elective vs acute coronary syndrome), and the type of stent implanted (bare-metal vs drug-eluting). In this article, we aim to provide a comprehensive, at-a-glance, overview of the management strategies, which are currently suggested for the peri-procedural, medium-term, and long-term periods following PCI-S in OAC patients. While acknowledging that most of the evidence has been obtained from patients on OAC because of atrial fibrillation, and with warfarin being the most frequently used VKA, we refer in this overview to the whole population of OAC patients undergoing PCI-S. We refer to the whole population of patients on OAC undergoing PCI-S also when OAC is carried out with NOAC rather than VKA, pointing out, when appropriate, the particular management issues.

Percutaneous rheolytic thrombectomy with the AngioJet System for the treatment of intermediate-risk acute pulmonary embolism: a case report and an appraisal of contemporary indications and technique.

Percutaneous mechanical thrombectomy (PMT) for treatment of clinically significant pulmonary embolism (PE) has been shown to be technically feasible and effective, aiming at thrombus resolution without increase in major bleeding. Despite its success, use of PMT in clinical practise has not become widespread, because it is challenging. Among several devices proposed, AngioJet rheolytic thrombectomy (ART) appears as the most effective and easy-to-use. We present the case of a 69-year-old woman who developed acute intermediate-risk PE, with right ventricular dysfunction and major myocardial necrosis, who was successfully treated by ART. The peculiarities of the case, toghether with the principles, tecnique and tips and tricks of ART, its effectiveness and potential complications are discussed.

Coronary stenting for ST-elevation myocardial infarction vs. other indications in patients on oral anticoagulation: any difference in in-hospital management and outcome?

AIM: The aim of this paper was to compare the in-hospital management and outcome of patients on oral anticoagulation (OAC) undergoing coronary artery stenting (PCI-S) for ST-elevation myocardial infarction (STEMI) vs. other indications. METHODS: One hundred and sixteen patients on OAC at the time of PCI-S who were prospectively enrolled in a multi-center, observational registry, were evaluated. Patients were segregated according to whether PCI-S was performed for STEMI (group 1) or other indications, such as non ST-elevation acute coronary syndromes, stable angina, silent ischemia, etc. (group 2), and the pharmacological and procedural management, as well as the in-hospital outcome, were compared. RESULTS: No significant differences were observed in vascular access site, sheath size and type of stent implanted, nor was significantly different the use of glycoprotein IIb/IIIa inhibitors, and the use and dose of intravenous unfractionated heparin. Although not statistically different, the in-hospital occurrence of death (3.7% vs. 1.1%; OR 3.3; 95% confidence intervals [CI] 0.2-56.0), stent thrombosis (3.7% vs. 1.1%; OR 3.3; 95% CI 0.2-56.0) and major bleeding (7.4% vs. 2.2%; OR 3.4; 95% CI 0.4-25.9) was consistently about 3-fold higher in group 1. CONCLUSION: The in-hospital pharmacological and procedural management of OAC patients undergoing PCI-S for STEMI vs. other indications appears not different. Although not significantly different however, the in-hospital occurrence of major bleeding, as well as of death and stent thrombosis, appears substantially higher in patients treated for STEMI, warranting therefore further larger, prospective studies.

Triple therapy of warfarin, aspirin and a thienopyridine for patients treated with vitamin K antagonists undergoing coronary stenting. A review of the evidence.

Dual antiplatelet treatment of aspirin and a thienopyridine (either ticlopidine or clopidogrel) is the standard of care in patients undergoing coronary artery stenting (PCI-S). Such treatment however, is not generally applicable in patients with concomitant indication for vitamin K antagonists (VKA), in whom therefore the optimal treatment is currently undefined. According to the limited available evidence, the management of these patients is substantially variable, but triple therapy of VKA, aspirin and a thienopyridine is the most frequently adopted. Both VKA and dual antiplatelet treatment in fact are warranted to actually prevent systemic thromboembolism and stent thrombosis, although an increased haemorrhagic risk might be associated with such therapy. A substantial incidence of bleeding has been effectively observed with triple therapy in a few, small, retrospective, observational series. The risk of haemorrhage appears to increase with the duration of treatment, although concomitant factors (i.e., advanced age, presence of gastrointestinal lesions, excessive anticoagulation or traumatic manoeuvres), rather than the administration of numerous antithrombotic agents in itself, may play a role. As expected, no thromboembolic or thrombotic events have been generally reported with such treatment. Because of the limited and poor quality data currently available on the management of patients with an indication for VKA undergoing PCI-S, large-scale registries and clinical trials are warranted to determine the optimal antithrombotic treatment in this patient subset, which is foreseen to progressively increase over the next years.

Contemporary antithrombotic treatment after coronary stenting in patients with indication for long-term anticoagulation.

AIM: Dual antiplatelet treatment with aspirin and a thienopyridine is the antithrombotic treatment recommended after percutaneous coronary intervention with stent implantation (PCI-S). Optimal treatment in patients with an indication for long-term oral anticoagulation (OAC) undergoing PCI-S is currently undefined. The aim of this study was to evaluate the contemporary management of these patients, and determine the safety and the efficacy of the various regimens. METHODS: A systematic review of the literature reporting on this issue was carried out. RESULTS: The adopted strategies showed substantial variability, and the regimens used included: substitution of OAC for dual antiplatelet therapy in 25-54% of cases, addition to OAC of a single antiplatelet agent in 12-25% and institution of triple therapy with OAC (or low-molecular-weight heparin), aspirin and a thienopyridine in about 60%. OAC was systematically aimed at a lower intensity in 33% of cases, whereas in another 29% this was pursued only when a high hemorrhagic risk was perceived. Both safety and efficacy of the various regimens appeared suboptimal, with a 30-day occurrence of major bleeding and thrombotic complications of 3-7% and 4%, respectively. CONCLUSIONS: Due to the suboptimal safety and/or efficacy of the various regimens adopted, the optimal antithrombotic treatment in patients with an indication for OAC undergoing PCI-S remains to be defined. Since the number of this patient subgroup is foreseen to progressively increase over the next years, large scale registries and clinical trials are warranted.

Subcutaneous enoxaparin following thrombolysis and intravenous unfractionated heparin in ST-elevation acute myocardial infarction: safety and efficacy of low vs full dose.

AIM: In ST-segment elevation myocardial infarction (STEMI) treated with fibrin-specific thrombolytic agents, early intravenous unfractionated heparin (UFH) is warranted. Low molecular weight heparin Enoxaparin currently represents an alternative to UFH, to be used until hospital discharge. Since optimal dosing of subcutaneous Enoxaparin is not standardized, we conducted an observational study to compare safety and efficacy of low (4,000 U once daily) vs full dose (100 U/kg twice daily) regimens. METHODS: All STEMI patients successfully treated with tenecteplase and intravenous UFH and referred to the Catheterization Laboratory between June 2002-November 2003 for predischarge coronary angiography, were evaluated. The primary end-point was the composite of hemorrhages and residual angina/reinfarction during Enoxaparin administration, whereas secondary end-points were occurrence of venous thromboembolism (VTE) during Enoxaparin administration, and infarct-related artery (IRA) patency rate at predischarge coronary angiography. RESULTS: Out of 123 patients, 57 (M/F 45/12, mean age 65.8+/-8.1 years) received low dose, and 66 (men/women 45/21, mean age 62.6+/-11.8 years) full dose subcutaneous Enoxaparin. The incidence of the composite primary end-point was comparable in both groups (19% vs 26%; P=NS). Also, null was the occurrence of VTE, whereas the IRA patency rate did not significantly differ in the 2 groups (84% vs 86% TIMI 3 and 11% vs 9% TIMI 2 flow grades; P=NS). CONCLUSIONS: In patients with STEMI undergoing successful recanalization with tenecteplase and intravenous UFH, low dose subcutaneous Enoxaparin appears preferable to full dose, in the light of comparable safety and clinical efficacy and superior easiness of use.

Increased cardiac troponin I on admission predicts in-hospital mortality in acute pulmonary embolism.

BACKGROUND: To investigate the frequency of cardiac troponin I (cTnI) increases in patients with pulmonary embolism (PE) and to assess the correlation between this finding, the clinical presentation, and outcomes. METHODS: Consecutive patients admitted to the coronary care unit with acute PE were prospectively enrolled between January 2000 and December 2001. cTnI was sequentially determined. Various cut off concentrations were analysed, but patients were categorised prospectively as having increased or no increased cTnI based on a cut off concentration of 0.6 ng/ml. The main outcome measure was in-hospital mortality. RESULTS: On admission, 14 of the 48 patients (29%) had cTnI concentrations greater than the receiver operating characteristic curve value used to diagnose acute myocardial infarction (> 0.6 ng/ml). Subsequently, six patients developed increases for an overall prevalence of 42% (20 of 42). The prevalence was higher when lower cut off concentrations were used: 73% (35 of 48) at the 99th centile and 60% (29 of 48) at the 10% coefficient of variability. Increased cTnI > 0.6 ng/ml was associated with a slower oxygen saturation (86 (7)% v 93 (4)%, p < 0.0001) and more frequent involvement of the main pulmonary arteries as assessed by spiral computed tomography (100% v 60%, p = 0.022). In-hospital mortality was 36% (5 of 14) of patients with increases > 0.6 ng/ml v 3% (1 of 42) of patients with lower concentrations (p = 0.008). Increased cTnI > 0.6 ng/ml on admission was the most powerful predictor of mortality (p = 0.046). CONCLUSIONS: In high risk patients with acute PE, cTnI was frequently detected on admission. It was the strongest independent predictor of mortality.

Enoxaparin for the treatment of acute myocardial infarction with persistent ST-segment elevation.

Enoxaparin (E) is a low-molecular-weight heparin which has been proven more effective than unfractionated heparin (UFH) for the treatment of non-ST-segment elevation acute coronary syndromes. Limited and inconclusive on the other hand, are the data on the use of E in acute myocardial infarction with persistent ST-segment elevation (STEAMI). Therefore, we performed a review of the literature in order to evaluate the level of evidence relative to the efficacy and safety of E in such a clinical setting. The effect of E in STEAMI has been evaluated in 7 clinical studies, including a total of about 9500 patients. Compared to placebo, E resulted more effective on the incidence of the combined end-point of death, re-infarction and recurrent angina in the study by Glick et al. and on the patency of the infarct-related artery in the AMI-SK study. Compared to UFH, E resulted more effective on the incidence of the combined end-point of death, reinfarction and unstable angina in the study by Baird et al. and of in-hospital re-infarction and refractory ischemia rates in both ASSENT-3 and ASSENT-3 PLUS, while the effect on the patency of the infarct-related artery, which was evaluated in HART-II and ENTIRE-TIMI 23, resulted non univocal. Overall, bleeding complications were more frequent than with placebo and comparable to UFH, with the exception of ASSENT-3 PLUS where pre-hospital administration of E was associated with a doubled incidence of intracranial bleeding (although only in patients older than 75 years). In conclusion, the administration of E, in association with aspirin and thrombolytics, already appears a possible therapeutic option for the treatment of STEAMI, due to its good efficacy and safety profile, along with its easiness of use. However, prior to have its use recommended, the current B level of evidence of a superior efficacy and safety compared to UFH needs to be reinforced. Further-more, some open issues relative to the use of E in particular settings (aged patients, in association with glycoprotein IIb/IIIa inhibitors and during percutaneous coronary revascularization) need to be clarified.

Outcome of percutaneous coronary angioplasty (PTCA) performed in a low-volume institution by low-volume operators, evaluated by means of the one-month major adverse cardiac event rate.

BACKGROUND: Since an inverse relationship between percutaneous coronary angioplasty (PTCA) case-load and in-hospital major adverse cardiac events (MACE) exists, we intended to evaluate the performance of low-volume PTCA operators, during the first year of our interventional program, by applying the more accurate index represented by the MACE rate within the first month. METHODS: The data relative to both the PTCA procedure and the control visit 3-4 weeks later, were retrospectively reviewed. Death, myocardial infarction and need for revascularization were the end-points evaluated, both globally and with respect to the individual operators. RESULTS: During 1999, 61 consecutive patients (53M, 8F; mean age: 59.9+/-10.4 years) were treated by two full-trained operators. Stable angina was the indication in 75% of cases. Comorbidities as diabetes and prior revascularization, were present in 16 and 5% of cases, respectively. Multivessel procedures were performed in 33% of cases, with a total number of lesions of 84 (77% A/B1 type). Stents were implanted in 70% of cases, as a bail-out in 12%. Procedural success rate was 93%. Overall one-month MACE rate was 3.3%, accounted for by 1 in-hospital emergency coronary surgery occurred to operator 1 (3.6% one-month MACE rate) and 1 elective coronary operation performed in a stable patient previously treated by operator 2 (3% one-month MACE rate). CONCLUSIONS: PTCA performed in a low-volume center by low-volume operators is not necessarily associated with a poor outcome, provided that adequate selection of low-risk cases is accomplished. Although only 52% of the Italian centers met in 1999 the recommended volume standards, reaching optimal case-load should anyway be pursued. Some time should however be conceded, provided that close monitoring of one-month MACE rate shows adequate performance of both the institution and the operators.

Ticlopidine versus oral anticoagulation for coronary stenting.

BACKGROUND: A 2-4 week course of ticlopidine plus aspirin following coronary stenting is considered effective in preventing thrombotic occlusion of the stented vessel and safe in regards to bleeding and peripheral vascular complications. However, rare, although potentially life-threatening haematological complications have been reported with this drug regimen. OBJECTIVES: To evaluate the efficacy and safety of ticlopidine plus aspirin versus oral anticoagulants after coronary stenting SEARCH STRATEGY: Electronic search of the Cochrane Library, Medline, Embase from 1991 to June 1999; references from trials and experts. SELECTION CRITERIA: Randomised controlled trials comparing ticlopidine plus aspirin versus oral anticoagulants (either with or without aspirin) after elective or bail out coronary stenting. DATA COLLECTION AND ANALYSIS: Three reviewers assessed trial quality and compiled data on outcomes including: total mortality, non fatal myocardial infarction and revascularization occurring within the first 30 days after hospitalization, stent thrombosis on angiography, major and minor bleeding, neutropenia, thrombocytopenia, thrombotic thrombocytopenic purpura. MAIN RESULTS: Four trials (n=2436 patients) were included. Ticlopidine plus aspirin compared to oral anticoagulants significantly reduced the risk of non-fatal acute myocardial infarction and revascularization at 30 days, combined negative events (mortality, myocardial infarction, revascularization at 30 days) (RR: 0.41; 95% CI: 0.25-0.69; NNT for 30 days: 22; 95% CI: 14-45), and major bleeding (RR in high quality studies: 0.24; 95% CI: 0.07-0.79). Ticlopidine plus aspirin compared to oral anticoagulants significantly increased the risk of eutropenia, thrombocytopenia and neutropenia (RR 5; 95% CI: 1.08-13.07; NNT for 30 days: 142; 95% CI: 76-1000). Ticlopidine plus aspirin vs oral anticoagulation did not affect all cause mortality. Ticlopidine plus aspirin significantly reduced the risk of stent thrombosis (angiography) which was seen only on studies with blinded outcome assessment (RR: 0.14; 95% CI: 0.03-0.60; NNT for 30 days: 33; 95% CI:16-166). Minor bleeding was reported only in one study and no studies recorded thrombotic thrombocytopenic purpura (TTP). REVIEWER'S CONCLUSIONS: Ticlopidine plus aspirin after coronary stenting is effective in reducing the risk of the revascularization, non fatal myocardial infarction and bleeding complications when compared with oral anticoagulants. No effect is observed on total mortality. However, the haematological side effects of ticlopidine are still a matter of concern, and strict monitoring of blood-cell counts is recommended. Physicians should also be aware of the possibility of rare although potentially life-threatening complications such as TTP

Appropriateness of the use of coronary angiography in a population of patients with ischemic heart disease.

BACKGROUND: Due to its pivotal role in the management of patients with ischemic heart disease, the use of coronary angiography has been continuously and progressively increasing over the years. However, an inappropriate rate of its utilization has been reported in 2 to 58% of cases. The aim of our study was therefore to evaluate the appropriateness of the indications for coronary angiography at our Institution. METHODS: All the patients undergoing coronary angiography at the catheterization laboratory of the Maggiore Hospital in Bologna during 1999 were evaluated. By retrospectively reviewing the data forms filled in at the time of insertion of the patient on the waiting list, the indications for coronary angiography were categorized as appropriate (class I/IIa), of uncertain value (class IIb) and inappropriate (class III), according to the guidelines of the American College of Cardiology/American Heart Association. In a blind fashion to this classification, the reports of coronary angiography were also reviewed to determine, both globally and in the different clinical subsets, the prevalence of significant coronary stenoses and of angiographically normal vessels. RESULTS: Class I/IIa indications were found in 72% of patients, as opposed to 28% in class lIb and none in class III. In the clinical subsets of stable angina, previous myocardial infarction and out-of-hospital cardiac arrest, the appropriateness was significantly higher, ranging from 74 to 100%, compared to recent myocardial infarction (63%) and unstable angina (59%) (accounting by itself for about one half of all class IIb indications). The overall prevalence of significant coronary artery disease was 87%, while in only 3% of cases did coronary angiography reveal normal vessels. CONCLUSIONS: In our population, the use of coronary angiography was highly appropriate and only seldom of uncertain value. The accurate noninvasive selection of patients which, in view of the limited access to the catheterization laboratory, we needed to perform before proceeding to coronary angiography probably played a major role in these results.

Current perspectives The diagnosis of acute pulmonary embolism. A review of the literature and current clinical practice.

The optimal approach to the diagnosis of acute pulmonary embolism is still controversial. The poor sensitivity and specificity of most of the clinical manifestations, the suboptimal accuracy of the majority of the laboratory and instrumental examinations and the highly variable local availability of the diagnostic resources, makes it in fact difficult for a univocal strategy to be adopted. Recently published practical guidelines, however, support the use of lung scanning (either ventilation/perfusion or only perfusion) as a first-line imaging test, since this approach allows for a correct diagnosis in most patients, after careful history taking, physical examination and electrocardiogram, chest X-ray and arterial blood gas analysis performance. When lung scanning is non-diagnostic, either serial non-invasive (i.e. ultrasonographic) evaluation of the lower limbs or pulmonary angiography should follow. Growing evidence is accumulating on the use of spiral computed tomography scanning either as an alternative or as a complement to lung scanning, while echocardiography should be reserved for the bedside evaluation of critically ill patients, when more validated techniques are not readily available. The role of plasma D-dimer measurement has yet to be defined, especially in hospitalized patients. In current clinical practice, however, these recommendations seem to be only partially followed. Depending in fact on the different characteristics of the populations examined in the seven available studies reporting on this issue, the use of the different diagnostic techniques appears highly variable. Although a standard diagnostic pathway does not seem applicable to all patients with suspected acute pulmonary embolism, further work is nonetheless needed in order to identify in different patient subsets the diagnostic approach capable of minimizing the use of diagnostic resources while obtaining the greatest amount of information.

Diagnostic approach to acute pulmonary embolism in a general hospital. A two-year analysis.

BACKGROUND: Several approaches have been proposed for the diagnosis of acute pulmonary embolism (PE), but little is known about the strategies effectively used in daily clinical practice. METHODS: Retrospective evaluation of the diagnostic strategy used in our institution in the patients (pts) discharged between January 1st 1995 and December 31st 1996 with diagnostic code 415.1, corresponding to acute PE in the International Classification of Disease. RESULTS: One-hundred-twenty-seven patients (49 M; 78 F; mean age: 71.5 +/- 15 years; range: 25-95) were identified. Electrocardiogram, chest X-ray, blood gas analysis and plasma D-dimer measurement were performed in 122 (96%), 121 (95%), 114 (90%) and 86 (68%) pts, respectively. Out of the 102 pts surviving the initial phase (early mortality: 20%), 83 (81%) underwent lung scintigraphy, 10 (10%) spiral CT scanning and 2 (2%) pulmonary angiography, while 7 (7%) were treated directly. Thirty of the 83 pts undergoing lung scintigraphy had non-diagnostic results, but only 8 of them underwent further investigation (with spiral CT in 6 cases and pulmonary angiography in 2 cases). Transthoracic echocardiography and ultrasonography of the lower limbs were used in 49 (48%) and 74 (73%) pts respectively, for diagnostic confirmation and to search for the embolic source. CONCLUSIONS: At our institution, where multiple and modern diagnostic facilities are available, ventilation/perfusion lung scanning still represents the most frequently used imaging technique. Spiral CT is employed quite often as an alternative to either lung scintigraphy or pulmonary angiography which, in turn, is used very seldom. Ultrasonography of the lower-limbs is widely utilized (although not in a serial manner and only as a second-line test), while the role of echocardiography appears to be marginal. Spiral CT, pulmonary angiography and lower-limb ultrasonography showed high diagnostic accuracy, while the accuracy of lung scintigraphy and echocardiography was confirmed as being suboptimal. However, due to the retrospective design of our study and the characteristics of our population, these results cannot be extrapolated to pts referred for suspected acute PE, in whom further investigations are thus warranted in order to identify the most cost-effective diagnostic approach.

[Initial experience with the use of abciximab in the salvage treatment of acute coronary thrombosis in the Hemodynamics Laboratory]. / Esperienza iniziale sull'uso di abciximab nel trattamento "di salvataggio" della trombosi coronarica acuta nel Laboratorio di Emodinamica.

The optimal treatment of acute thrombotic complications in the Catheterization Laboratory has not been defined yet, due to the limited efficacy shown by various pharmacological regimens, even when associated to coronary angioplasty (PTCA). The aim of our study was therefore to evaluate the effects of abciximab (ReoPro), a new potent inhibitor of the platelet glycoprotein IIb/IIIa, when administered as a "rescue" treatment for acute thrombotic coronary occlusion during diagnostic or interventional procedures. Sixteen patients (12 males, 4 females, mean age 59.3 +/- 9.2 years, range 43-77 years), with unstable angina and consecutively treated with abciximab due to clinical instability attributable to coronary thrombosis angiographically proven during PTCA (9 cases) or diagnostic angiography (7 cases), were identified. The individual angiographic films and medical records were then reviewed in order to evaluate the effects of treatment on coronary flow, thrombus size and occurrence of in-hospital adverse events: death, non-fatal acute myocardial infarction (AMI), need for urgent myocardial revascularization and hemorrhage. The administration of abciximab, in association with PTCA (associated in turn with stent implantation in 8 cases), induced a significant increase of coronary TIMI flow grade (0.3 +/- 0.6 vs 2.4 +/- 0.9; p < 0.05) and a significant decrease of thrombus "score" (size) 2.4 +/- 0.9 vs 1.3 +/- 0.6; p < 0.01). No deaths nor need for urgent myocardial revascularization were observed; in 31% of cases (5 patients) evolution towards AMI occurred, while however 94% of cases (15 patients) had a coronary occlusion before treatment. No major hemorrhagic complications were observed, while in 12% of cases (2 patients) a groin hematoma associated with moderate hemoglobin drop, developed. In conclusion, the administration of abciximab, associated with the common "rescue" interventional procedures, in patients with acute thrombotic coronary occlusion in the Catheterization Laboratory, appears to be effective in restoring adequate coronary flow and reducing the thrombus size (limiting therefore the evolution towards AMI), and safe, not having been associated with significant hemorrhagic complications.