RESUMEN
Bicycloalkyl groups have been previously described as phenyl group bioisosteres. This article describes the synthesis of new building blocks allowing their introduction into complex molecules, and explores their use as a means to modify the physicochemical properties of drug candidates and improve the quality of imaging agents. In particular, the replacement of an aromatic ring with a bicyclo[1.1.1]pentane-1,3-diyl (BCP) group improves aqueous solubility by at least 50-fold, and markedly decreases nonspecific binding (NSB) as measured by CHI(IAM), the chromatographic hydrophobicity index on immobilized artificial membranes. Structural variations with the bicyclo[2.2.2]octane-1,4-diyl group led to more lipophilic molecules and did not show the same benefits regarding NSB or solubility, whereas substitutions with cubane-1,4-diyl showed improvements for both parameters. These results confirm the potential advantages of both BCP and cubane motifs as bioisosteric replacements for optimizing para-phenyl-substituted molecules.
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Compuestos Bicíclicos con Puentes/química , Membranas Artificiales , Compuestos de Anilina/química , Compuestos Bicíclicos con Puentes/síntesis química , Ácidos Carboxílicos/química , Interacciones Hidrofóbicas e Hidrofílicas , Ligandos , SolubilidadRESUMEN
BACKGROUND: Whether cyclosporine A (CsA) has beneficial effects in reperfused myocardial infarction (MI) is debated. OBJECTIVES: This study investigated whether CsA improved ST-segment resolution in a randomized, multicenter phase II study. METHODS: The authors randomly assigned 410 patients from 31 cardiac care units, age 63 ± 12 years, with large ST-segment elevation MI within 6 h of symptom onset, Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 to 1 in the infarct-related artery, and committed to primary percutaneous coronary intervention, to 2.5 mg/kg intravenous CsA (n = 207) or control (n = 203) groups. The primary endpoint was incidence of ≥70% ST-segment resolution 60 min after TIMI flow grade 3. Secondary endpoints included high-sensitivity cardiac troponin T (hs-cTnT) on day 4, left ventricular (LV) remodeling, and clinical events at 6-month follow-up. RESULTS: Time from symptom onset to first antegrade flow was 180 ± 67 min; a median of 5 electrocardiography leads showed ST-segment deviation (quartile [Q]1 to Q3: 4 to 6); 49.8% of MIs were anterior. ST-segment resolution ≥70% was found in 52.0% of CsA patients and 49.0% of controls (p = 0.55). Median hs-cTnT on day 4 was 2,160 (Q1 to Q3: 1,087 to 3,274) ng/l in CsA and 2,068 (1,117 to 3,690) ng/l in controls (p = 0.85). The 2 groups did not differ in LV ejection fraction on day 4 and at 6 months. Infarct site did not influence CsA efficacy. There were no acute allergic reactions or nonsignificant excesses of 6-month mortality (5.7% CsA vs. 3.2% controls, p = 0.17) or cardiogenic shock (2.4% CsA vs. 1.5% controls, p = 0.33). CONCLUSIONS: In the CYCLE (CYCLosporinE A in Reperfused Acute Myocardial Infarction) trial, a single intravenous CsA bolus just before primary percutaneous coronary intervention had no effect on ST-segment resolution or hs-cTnT, and did not improve clinical outcomes or LV remodeling up to 6 months. (CYCLosporinE A in Reperfused Acute Myocardial Infarction [CYCLE]; NCT01650662; EudraCT number 2011-002876-18).
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Ciclosporina/administración & dosificación , Electrocardiografía , Infarto del Miocardio/terapia , Reperfusión Miocárdica/métodos , Función Ventricular Izquierda/fisiología , Remodelación Ventricular/efectos de los fármacos , Angiografía Coronaria , Relación Dosis-Respuesta a Droga , Ecocardiografía , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/administración & dosificación , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/fisiopatología , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Objective of this study was to assess the clinical performance of bioresorbable vascular scaffold (BVS) compared to everolimus-eluting stent (EES) in subjects with ST-segment elevation myocardial infarction (STEMI). We included all consecutive patients with STEMI who underwent percutaneous coronary intervention (PCI) with BVS implantation in centers participating to the Italian ABSORB Prospective Registry (BVS-RAI) and PCI with EES in the same centers during the same period. The 2 groups were compared. The primary end point was patient-oriented composite end point (POCE) including cardiac death, myocardial infarction, and target lesion revascularization (TLR) at the longest available follow-up. BVS or EES thrombosis at follow-up was also evaluated. Of the 563 patients with STEMI included, 122 received BVS and 441 EES. Procedural success was obtained in 549 (97.5%) cases without significant differences between the 2 groups (BVS 99.3% vs EES 97.0%, p = 0.2). At a median of 220-day (interquartile range 178 to 369) follow-up, no significant differences were observed in terms of POCE (BVS 4.9% vs EES 7.0%, p = 0.4); death (BVS 0.8%, EES 2.0%, p = 0.4), MI (BVS 4.1%, EES 2.0%, p = 0.2), TLR (BVS 4.1%, EES 4.5%, p = 0.8), device thrombosis (BVS 2.5%, EES 1.4%, p = 0.4). All TLR cases were successfully managed with re-PCI in both groups. A propensity matching of the study populations showed no significant differences regarding POCE at the longest available follow-up (odds ratio 0.53, 0.1 to 4.3). In conclusion, in this direct prospective comparison, BVS was associated with similar clinical results compared to EES in the STEMI setting. Larger and adequately powered randomized trials are needed to fully assess the potential clinical benefit of BVS versus the current standard of care in patients with STEMI.
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Implantes Absorbibles , Stents Liberadores de Fármacos , Infarto del Miocardio/cirugía , Intervención Coronaria Percutánea/métodos , Sirolimus/análogos & derivados , Andamios del Tejido , Anciano , Antineoplásicos , Angiografía Coronaria , Electrocardiografía , Everolimus , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/farmacología , Incidencia , Italia/epidemiología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Diseño de Prótesis , Sirolimus/farmacología , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of this study was to collect information to understand how citizens perceive the National Health System (NHS), and what is the degree of confidence they have in the NHS. METHODS: We carried out an opinion poll with the Demos & Pi group on the perception of the NHS by Italian citizens, with particular reference to the activities related to cardiology, by interviewing 2311 people with a set of 33 questions, about the perception of their health status, lifestyles, the propensity to use public or private services, consideration of the level of the NHS, and the trust in the medical profession. The subjects included were also preliminarily stratified according to the presence or absence of heart disease. RESULTS: Overall, Italian citizens express a high level of satisfaction for the NHS (on average, 65% of approval rating), including the whole professional staff, hoping that the NHS will be kept appropriately funded. The result is even better in the subset of interviewed citizens, who suffered from cardiovascular disease. People also consider the NHS an essential requirement to ensure equity in access to medical treatment and to keep costs competitive, even compared to private healthcare. The NHS major weakness remains the waiting lists, which are considered too long for diagnostic procedures and ordinary interventions. CONCLUSIONS: There is a widespread positive feeling among Italian citizens concerning the role and functioning of the NHS. Such opinion, shared by the whole country, should be taken into account when the time will come to define strategies for health policy of the Italian society in the near future.
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Cardiología , Atención a la Salud , Política de Salud , Programas Nacionales de Salud , Satisfacción del Paciente , Adolescente , Adulto , Anciano , Femenino , Encuestas de Atención de la Salud , Cardiopatías/diagnóstico , Cardiopatías/terapia , Humanos , Italia , Masculino , Persona de Mediana Edad , Medicina Estatal , Encuestas y CuestionariosRESUMEN
AIMS: In this multicentre prospective registry we sought to evaluate the immediate and midterm clinical outcomes following single or multiple overlapping bioresorbable vascular scaffold (BVS) implantation in the STEMI setting. METHODS AND RESULTS: A prospective cohort analysis was performed on all STEMI patients who underwent primary PCI with BVS implantation. Between December 2012 and February 2014, 1,232 STEMI patients underwent primary PCI at the participating centres. Of these, 74 (6.0%) received a BVS, 18 (24.3%) of them were multiple and overlapping. Procedural success was obtained in 72 (97.3%) cases without differences between the groups (overlapping BVS 100% vs. single BVS 96.4%, p=0.5). One patient experienced a reinfarction due to subacute BVS thrombosis which was successfully managed with balloon-only PCI while the other patient had a "slow-flow" phenomenon (final TIMI flow 2). At six-month follow-up, two non-fatal MI (2.7%), three target lesion revascularisations (4.1%), and one subacute BVS thrombosis were reported in three patients (one [5.6%] overlapping BVS and two [3.6%] in the single BVS group, p=0.5). All the events were successfully managed with re-PCI. CONCLUSIONS: BVS implantation in STEMI patients can be successfully performed with a high procedural success rate and encouraging midterm outcomes. Larger randomised trials and longer follow-up are needed to assess the potential clinical benefit of BVS versus new-generation DES in this setting.
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Implantes Absorbibles , Stents Liberadores de Fármacos , Everolimus/uso terapéutico , Infarto del Miocardio/cirugía , Intervención Coronaria Percutánea , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/métodos , Estudios Prospectivos , Sistema de Registros , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: To obtain further, and more focused, information on the efficacy and safety of the antithrombotic regimens, including triple therapy (TT) of warfarin, aspirin, and clopidogrel; dual therapy (DT) of warfarin and single antiplatelet agent (aspirin or clopidogrel); and dual-antiplatelet therapy (DAPT) of aspirin and clopidogrel, prescribed to patients on oral anticoagulation (OAC) undergoing percutaneous coronary intervention with stent (PCI-S). BACKGROUND: The true efficacy and safety of TT, DT, and DAPT in OAC patients undergoing PCI-S is largely undefined. METHODS: We analyzed the database of the prospective, multicenter WARfarin and coronary STENTing (WAR-STENT) registry (ClinicalTrials.gov identifier NCT00722319), only including the post-discharge period. RESULTS: Of the 401 patients discharged alive from index hospitalization, 339 (85%), 20 (5%), and 42 (10%) were prescribed TT, DT, and DAPT, respectively. Throughout a mean follow-up of 368.3 ± 22.8 days, major adverse cardiovascular events (MACE) (including cardiovascular death, myocardial infarction, repeat revascularization, stent thrombosis, and thromboembolism), total bleeding, major bleeding, and combination of MACE plus total bleeding were comparable across the three treatment groups. The absolute rate of major bleeding with TT was 4%. The antithrombotic treatment actually ongoing at major bleeding was TT in 44%, DT in 50%, and DAPT in 6% of cases. CONCLUSION: In the real-world population of OAC patients undergoing PCI-S in the WAR-STENT registry, the three antithrombotic regimens of TT, DT, and DAPT showed comparable efficacy and safety. Due to several limitations, our data cannot be considered conclusive in confuting the current recommendations to prescribe TT. Further properly designed and sized studies are warranted.
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Angioplastia Coronaria con Balón , Aspirina/efectos adversos , Aspirina/uso terapéutico , Stents Liberadores de Fármacos , Ticlopidina/análogos & derivados , Warfarina/efectos adversos , Warfarina/uso terapéutico , Administración Oral , Clopidogrel , Bases de Datos Bibliográficas , Quimioterapia Combinada , Estudios de Seguimiento , Hemorragia/inducido químicamente , Estudios Prospectivos , Sistema de Registros , Ticlopidina/efectos adversos , Ticlopidina/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Hypertension continues to be a major burden of public health concern despite the recent advances and proven benefit of pharmacological therapy. A certain subset of patients has hypertension resistant to maximal medical therapy and appropriate lifestyle measures. A novel catheter-based technique for renal denervation (RDN) as a new therapeutic avenue has great promise for the treatment of refractory hypertension. SUMMARY: This review included the physiology of the renal sympathetic nervous system and the renal nerve anatomy. Furthermore, the RDN procedure, technology systems, and RDN clinical trials as well as findings besides antihypertensive effects were discussed. Findings on safety and efficacy seem to suggest that renal sympathetic denervation could be of therapeutic benefit in refractory hypertensive patients. Despite the fast pace of development in RDN therapies, only initial and very limited clinical data are available. Large gaps in knowledge concerning the long-term effects and consequences of RDN still exist, and solid, randomized data are warranted.
RESUMEN
BACKGROUND: Coronary bifurcation lesions represent a difficult problem regularly confronting interventional cardiologist, in part due to the lack of dedicated device. OBJECTIVE: To investigate the feasibility, safety and effectiveness of the Tryton Side Branch Stent (Tryton Medical, Durham, NC, USA), a dedicated bare metal stent deployed in conjunction with a standard drug-eluting stent to treat bifurcation lesions. METHODS: The SAFE-TRY is a prospective single arm multicenter registry including patients with de novo bifurcation lesions in native coronary arteries and syntax score <32. The primary endpoint was target vessel failure (TVF) at 30 days that comprised cardiac death, target vessel myocardial infarction and clinically driven target vessel revascularization. Secondary endpoints included device, angiographic and procedural success, 9-month major adverse cardiac and cerebrovascular event (MACCE), and stent thrombosis (ST) rates (ClinicalTrials.gov identifier: NCT01174433). RESULTS: Among 252 enrolled patients, 24% had diabetes and 35.3% unstable angina. True bifurcation lesions involving both branches occurred in 96.8% of cases with Medina classification 1.1.1 in 62%. The left anterior descending artery and the left main were treated in 70% and 8.3% of the patients, respectively. A 6 Fr guide catheter was used in 61% of the cases. Device, angiographic and procedural success rates were 99.6%, 99.6% and 97.2% respectively. The 30-day TVF was 2.8%; the 9-month MACCE rate was 13.7%, with target lesion revascularization being 4.4%. No definite ST occurred. CONCLUSIONS: This prospective, multicenter study confirmed the feasibility, safety and effectiveness of the Tryton Side Branch Stent to treat patients with de novo complex bifurcation lesions.
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Angioplastia Coronaria con Balón/instrumentación , Enfermedad de la Arteria Coronaria/terapia , Stents Liberadores de Fármacos/efectos adversos , Stents/efectos adversos , Anciano , Angioplastia Coronaria con Balón/estadística & datos numéricos , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Reestenosis Coronaria/epidemiología , Trombosis Coronaria/epidemiología , Vasos Coronarios/patología , Stents Liberadores de Fármacos/estadística & datos numéricos , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros/estadística & datos numéricos , Stents/estadística & datos numéricos , Resultado del TratamientoRESUMEN
OBJECTIVES: This study sought to investigate the efficacy and performance of the XIENCE V everolimus-eluting stent (EES) (Abbott Vascular, Santa Clara, California) in the treatment of de novo coronary lesions in patients with 2- to 3-vessel multivessel coronary artery disease (MV-CAD). BACKGROUND: Drug-eluting stents (DES) have emerged as an alternative to conventional coronary artery bypass surgery in patients with MV-CAD although first-generation DES yielded inferior efficacy and safety compared with surgery. METHODS: Prospective, randomized (1:1), multicenter feasibility trial was designed to assess angiographic efficacy of EES compared with the TAXUS paclitaxel-eluting stent (PES) in 200 patients, and a prospective, open-label, single-arm, controlled registry was designed to analyze the clinical outcome of EES at 1-year follow-up in 400 MV-CAD patients. For the randomized trial, the primary endpoint was in-stent late loss at 9 months. For the registry, the primary endpoint was a composite of all-cause death, myocardial infarction, and ischemia-driven target vessel revascularization at 12 months. RESULTS: The primary endpoint per single lesion was significantly lower in the EES group compared with the PES group (-0.03 ± 0.49 mm vs. 0.23 ± 0.51 mm, p = 0.001). Similar results were observed when analyzing all lesions (0.05 ± 0.51 mm vs. 0.24 ± 0.50 mm, p < 0.001). Clinical outcome at 1 year yielded a composite of major adverse cardiac events of 9.2% in the single-arm registry, and 11.1% and 16.5% in the EES and PES randomized groups, respectively (p = 0.30). CONCLUSIONS: The EXECUTIVE trial was a randomized pilot trial dedicated to the comparison of the efficacy of 2 different DES among patients with 2- to 3-vessel MV-CAD. The study shows lower in-stent late loss at 9 months with the EES XIENCE V compared with the PES TAXUS Libertè, and a low major adverse cardiac event rate at 1 year in patients with 2-to 3-vessel MV-CAD. (EXECUTIVE [EXecutive RCT: Evaluating XIENCE V in a Multi Vessel Disease]; NCT00531011).
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Fármacos Cardiovasculares/administración & dosificación , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/terapia , Vasos Coronarios/efectos de los fármacos , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea/instrumentación , Sirolimus/análogos & derivados , Anciano , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/fisiopatología , Reestenosis Coronaria/etiología , Reestenosis Coronaria/prevención & control , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Everolimus , Estudios de Factibilidad , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Infarto del Miocardio/prevención & control , Paclitaxel/administración & dosificación , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Diseño de Prótesis , Sistema de Registros , Sirolimus/administración & dosificación , Factores de Tiempo , Resultado del TratamientoRESUMEN
A synthesis of all four stereoisomers of 3-(tert-butoxycarbonyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid has been developed, thereby significantly shortening the known literature procedures for the syntheses of these unnatural amino acids. With a simple adjustment of the reaction conditions, we were able to obtain either pure cis or trans acid. Optical resolution was accomplished via diastereomeric salt formation or alternatively via chromatography on a chiral stationary phase. Finally, ab initio calculations gave an explanation for the observed cis selectivity in the initial step.
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Aminoácidos/síntesis química , Compuestos Bicíclicos Heterocíclicos con Puentes/síntesis química , Ciclohexanos/síntesis química , Aminoácidos/química , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Ciclohexanos/química , Estructura Molecular , Teoría Cuántica , EstereoisomerismoAsunto(s)
Adhesión a Directriz , Revascularización Miocárdica/normas , Guías de Práctica Clínica como Asunto , Síndrome Coronario Agudo/fisiopatología , Síndrome Coronario Agudo/cirugía , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/cirugía , Humanos , Educación del Paciente como AsuntoRESUMEN
Adjunctive therapy with abciximab during primary percutaneous coronary intervention (PPCI) in patients with ST-elevation myocardial infarction (STEMI) determines a better short-term outcome compared to placebo. Tirofiban and eptifibatide represent a valid option with lower cost, but these have been less studied. The aim of the present study was to combine all randomized trials and registries to demonstrate the noninferiority of tirofiban and eptifibatide compared to abciximab in patients with STEMI treated with PPCI. We identified 6 randomized trials and 4 registries. Overall, 4,653 received small molecules and 2,696 abciximab, and the rate of combined death and nonfatal reinfarction did not differ (4.6% vs 4.5%, odds ratio 0.99, 95% confidence interval [CI] 0.78 to 1.27, p = 0.95) up to 30 days of follow-up, with an absolute difference of 0.1% (95% CI -1.06 to 0.8). Because the noninferiority limit was set at +1.5%, and because the upper point estimate (0.8%) of the 95% CI did not cross the prespecified limit, the noninferiority of the small molecules was documented. In-hospital major bleeding was also similar (8.8% vs 6.1%, odds ratio 0.92, 95% CI 0.75 to 1.13, p = 0.43). Sensitivity analysis comparing randomized trials to registries and tirofiban or eptifibatide to abciximab did not show any significant differences. In conclusion, our results documented noninferiority of "small molecules" compared to abciximab and, therefore, support their alternative use as adjunctive therapy during PPCI for patients with STEMI.
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Infarto del Miocardio/terapia , Inhibidores de Agregación Plaquetaria/uso terapéutico , Abciximab , Anciano , Angioplastia Coronaria con Balón , Anticuerpos Monoclonales/uso terapéutico , Electrocardiografía , Eptifibatida , Femenino , Humanos , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Masculino , Persona de Mediana Edad , Péptidos/uso terapéutico , Tirofibán , Resultado del Tratamiento , Tirosina/análogos & derivados , Tirosina/uso terapéuticoRESUMEN
BACKGROUND: Myocardial revascularization with drug-eluting stents (DESs) is emerging as an alternative to conventional coronary artery bypass surgery in patients with multivessel coronary artery disease (MV-CAD). First-generation DESs have yielded equivalent safety results at mid-term compared with surgery, but inferior efficacy in preventing the recurrence of ischemic symptoms. The outcome of percutaneous coronary intervention with a second-generation everolimus DES as compared with a paclitaxel DES in patients with MV-CAD has not been established. AIM OF THE STUDY: The aim of the study is the assessment of the efficacy and performance of the XIENCE V everolimus-eluting stent in the treatment of de-novo coronary artery lesions in patients with MV-CAD. STUDY DESIGN: The study is composed of two parts: a prospective, double arm, randomized multicenter trial to assess the angiographic efficacy of the XIENCE V everolimus-eluting coronary stent system (EECSS) compared with the Taxus Liberté Paclitaxel Eluting Coronary Stent System (Taxus Liberté Stent) and a prospective, open-label, single arm, controlled registry to analyze the clinical efficacy and safety of XIENCE V EECSS at mid-term and long-term follow-up in patients treated for MV-CAD. ENDPOINTS: For the EXECUTIVE randomized trial, the primary endpoint is in-stent late lumen loss at 9 months. For the EXECUTIVE registry, the primary endpoint is a composite of all death, myocardial infarction (Q-wave and non-Q-wave), and ischemia-driven target vessel revascularization at 12 months. The study will be conducted at 30 study centers in Italy and 600 patients will be enrolled in total: 200 patients will be enrolled (1: 1) in the randomized trial and 400 patients will enter the registry. SAMPLE SIZE: It was calculated that, assuming a mean in-stent late lumen loss of 0.20 +/- 0.41 mm in the XIENCE V EECSS arm and 0.30 +/- 0.53 mm in the Taxus Liberté stent arm, and a noninferiority margin delta of 0.12 (according to the SPIRIT III results), the analysis of 81 lesions per arm would provide over 90% power. Therefore, 200 patients will be enrolled to account for dropouts. CONCLUSION: The present study is expected to provide as yet unavailable information about the performance of second-generation stents in the specific setting of patients with MV-CAD.
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Enfermedad de la Arteria Coronaria/cirugía , Stents Liberadores de Fármacos , Inmunosupresores/administración & dosificación , Proyectos de Investigación , Sirolimus/análogos & derivados , Angiografía , Implantación de Prótesis Vascular , Protocolos Clínicos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Análisis Costo-Beneficio , Everolimus , Humanos , Revascularización Miocárdica , Estudios Prospectivos , Sirolimus/administración & dosificaciónRESUMEN
BACKGROUND: Atrial fibrillation is the most common arrhythmia in clinical practice. Its treatment is still widely debated due to the large variety of therapeutic options. Radiofrequency catheter ablation (RFCA) around pulmonary vein ostia and in the left atrium has been proposed as a technique to cure atrial fibrillation and is now performed with increasing success worldwide. However, few randomized controlled trials (RCTs) are available. Some of these have been published recently and are not yet included in meta-analyses. OBJECTIVES: We conducted a meta-analysis to summarize the current evidence base for the efficacy and safety of RFCA in patients with atrial fibrillation. METHODS: We searched electronic databases for relevant RCTs comparing RFCA with antiarrhythmic drugs for the management of atrial fibrillation. Recurrence of any atrial tachyarrhythmia (including atrial fibrillation, atrial flutter and atrial tachycardia) and rate of complications and adverse events were the end-points of the analysis. The results are reported as relative risk and 95% confidence interval, calculated using RevMan 5. RESULTS: A total of eight RCTs were identified including 844 patients. Overall, 98 (23.2%) of 421 patients in the treatment group and 324 (76.6%) of 423 patients in the control group had atrial tachyarrhythmia recurrence. RFCA decreased atrial tachyarrhythmia recurrence by 71% (relative risk 0.29, 95% confidence interval 0.20-0.41, P < 0.00001, with random effects model). Fewer complications and adverse events were reported in the ablation group compared with the control group (relative risk 0.72, 95% confidence interval 0.40-1.30, P = 0.28, with random effects model). CONCLUSION: In selected patients with atrial fibrillation, RFCA is a relatively effective and well-tolerated procedure to cure atrial fibrillation. Even though the results of our systematic review favour ablation therapy, large, well-designed RCTs are needed to confirm the efficacy and safety of RFCA for the management of atrial fibrillation.
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Antiarrítmicos/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/cirugía , Ablación por Catéter , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an unusual cause of acute myocardial ischemia that in almost 50% of cases is followed by sudden death. The increasing frequency of SCAD diagnosis may reflect the widespread use of coronary angiography and percutaneous coronary interventions in acute coronary syndromes (ACS). The incidence of SCAD is estimated between 0.1 and 0.28% of all ACS or sudden deaths evaluated by angiography or by anatomical examination, respectively. Most published data available so far deal with single case reports and probably the real incidence of this disease is underestimated. Some predisposing conditions to SCAD are well known and include Marfan syndrome, pregnancy and peripartum state, drug abuse and some anatomical abnormalities of the coronary arteries like aneurysms and severe kinking. The most appropriate therapeutic approach to SCAD is still controversial and decision making is often based on the clinical presentation, extent of dissection and amount of ischemic myocardium. OBJECTIVES AND METHODS: The purpose of this multicenter prospective registry, named DISCOVERY (DISsection of COronary arteries: Veneto and Emilia RegistrY), with a case-control group is to try to assess the role of SCAD in the pathogenesis of ACS. The primary endpoint is the occurrence of major adverse cardiovascular events related to the therapeutic strategy in the acute phase and in the mid-term follow-up. The secondary endpoints are the estimation of the prevalence of SCAD in the pathogenesis of ACS, the association or disassociation of SCAD with presumptive predisposing factors, the appreciation of the timing and extent of multivessel involvement when present, the occurrence of vascular and ocular comorbidities (i.e. carotid dissection and ocular lens abnormalities), the evaluation of the immediate success and the mid-term outcome of percutaneous coronary interventions and the definition of the role of intravascular ultrasound in diagnosis and treatment of SCAD. The enrollment of approximately 50 patients with SCAD is planned. A planned control group of patients of comparable age, sex and clinical presentation will allow us to identify potential peculiar or specific aspects of SCAD in any phase of the disease. CONCLUSION: The DISCOVERY multicenter registry, with a case-control group, is the first large prospective study aimed at assessing the role of SCAD in the pathogenesis of ACS and at identifying the role of different therapeutic strategies in this unusual, multifaceted and probably underestimated pathologic condition.
Asunto(s)
Síndrome Coronario Agudo/etiología , Disección Aórtica/complicaciones , Aneurisma Coronario/complicaciones , Sistema de Registros , Proyectos de Investigación , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/mortalidad , Síndrome Coronario Agudo/terapia , Disección Aórtica/diagnóstico , Disección Aórtica/mortalidad , Disección Aórtica/terapia , Angioplastia Coronaria con Balón , Estudios de Casos y Controles , Aneurisma Coronario/diagnóstico , Aneurisma Coronario/mortalidad , Aneurisma Coronario/terapia , Angiografía Coronaria , Humanos , Italia/epidemiología , Prevalencia , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
PURPOSE: In patients on oral anticoagulation (OAC) undergoing coronary stenting (PCI-S), procedural management and in-hospital outcome have never been specifically and prospectively investigated. Also, the contribution of early bleeding to the relevant hemorrhagic rate reported at follow-up with triple therapy of OAC, aspirin, and clopidogrel is largely unknown. METHODS: Consecutive patients with indication for OAC undergoing PCI-S at 5 centers were enrolled and prospectively evaluated. RESULTS: Out of 3410 patients undergoing PCI-S in the study period, indication for OAC was present in 4.8%. Femoral approach and bare metal stents were the most frequently used. During PCI-S, OAC was continued in about 30% of patients, whereas in about 20% heparin bridging was carried out. Glycoprotein IIb/IIIa inhibitors were rarely used (11%), whereas a standard bolus of unfractionated heparin was given in 93% of cases. Major adverse cardiovascular events (MACE) occurred in 4.8% of patients and major bleeding in 4.3%. No predictors of MACE or bleeding were identified, although the femoral approach was of borderline significance for major bleeding (OR 4.6, 95% CI 1.0-20.8; P = 0.05). A history of previous hemorrhage (OR 5.3, 95% CI 1.6-18.1; P = 0.007) predicted Carbofilm-coated stent implantation. CONCLUSIONS: A limited, albeit clinically relevant, proportion of patients undergoing PCI-S has indication for OAC. Procedural management appears not substantially different from that of common patients. In-hospital major bleeding is relevant and should be taken into account when evaluating the overall hemorrhagic rate at a medium- to long-term follow-up.
Asunto(s)
Angioplastia Coronaria con Balón , Anticoagulantes/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Vasos Coronarios , Stents Liberadores de Fármacos , Hospitalización/estadística & datos numéricos , Cuidados Intraoperatorios , Inhibidores de Agregación Plaquetaria/uso terapéutico , Resultado del Tratamiento , Intervalos de Confianza , Enfermedad de la Arteria Coronaria/terapia , Humanos , Modelos Logísticos , Oportunidad Relativa , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: The optimal management of patients on oral anticoagulation (OAC) undergoing coronary stenting (PCI-S) is currently undefined. Available evidence suggests that triple therapy of OAC, aspirin and clopidogrel is the most effective, though associated with a relevant incidence of major bleeding. Nearly all data, however, derive from small-size, retrospective studies in which the occurrence of bleeding has seldom been reported according to the ongoing therapy, and the relative contribution to overall bleeding of early haemorrhages has rarely been analysed separately. We design a prospective multicentre registry, which will include patients on OAC undergoing PCI-S. OBJECTIVE: To prospectively evaluate the post-PCI-S antithrombotic treatment in patients on OAC, relative safety and efficacy of the various regimens, and periprocedural technical and pharmacological management. STUDY DESIGN: Sixty to seventy Italian centres will be enlisted. Patients on OAC at the time of PCI-S will be enrolled and followed up for 12 months. The primary endpoint will be the composite of major/minor bleeding, major adverse cardiac events (e.g., need for urgent re-revascularization, myocardial infarction, death) (MACE), arterial and/or venous thrombosis/thromboembolism. Secondary endpoints will be: major/minor bleeding, MACE, stent thrombosis, arterial or venous thromboembolic complications or both, and the need for blood transfusions. EXPECTED RESULTS AND IMPLICATIONS: This multicentre, prospective registry of patients on OAC undergoing PCI-S will provide for the first time extensive and updated information on current clinical practice, and on the safety and efficacy of the various strategies. As a consequence, clues for the optimal management of this patient subset will be obtained.
Asunto(s)
Angioplastia Coronaria con Balón/instrumentación , Anticoagulantes/administración & dosificación , Enfermedad de la Arteria Coronaria/terapia , Stents , Tromboembolia/prevención & control , Trombosis/prevención & control , Warfarina/administración & dosificación , Administración Oral , Angioplastia Coronaria con Balón/efectos adversos , Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Humanos , Italia , Estudios Prospectivos , Sistema de Registros , Proyectos de Investigación , Medición de Riesgo , Tromboembolia/etiología , Trombosis/etiología , Warfarina/efectos adversosRESUMEN
Percutaneous coronary intervention (PCI) is routinely performed in patients with non-ST elevation acute coronary syndromes after pretreatment with clopidogrel and periprocedural administration of unfractionated heparin on a weight-adjusted basis. Although activated clotting time (ACT) monitoring is encouraged to verify the adequacy of anticoagulation during the procedures, this is not a common practice in many laboratories. The authors describe 4 cases of patients with bifurcation lesions involving the left anterior descending coronary artery, who developed periprocedural thrombosis with acute transmural ischemia. All patients had inadequate ACT measurements, despite conventional heparin dosage and ongoing clopidogrel treatment. In order to achieve complete anticoagulation, patients were switched to bivalirudin, which determined a prompt effect on measured ACT. This therapeutic regimen, coupled with further intervention, allowed resolution of the thrombotic complication without bleeding. This report suggests the feasibility of a strategy of bivalirudin use in patients who have some degree of heparin 'resistance' in the setting of complicated PCI.
Asunto(s)
Síndrome Coronario Agudo/terapia , Angioplastia Coronaria con Balón/efectos adversos , Anticoagulantes/administración & dosificación , Trombosis Coronaria/tratamiento farmacológico , Hirudinas/administración & dosificación , Fragmentos de Péptidos/administración & dosificación , Anciano , Trombosis Coronaria/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/administración & dosificación , Resultado del TratamientoRESUMEN
We report two cases in which intra-aortic balloon pump (IABP) was used successfully as a bridge to cardiac resynchronization therapy (CRT) to treat patients with refractory systolic heart failure. The study was designed to assess the acute haemodynamic effects of IABP coupled with CRT using standard haemodynamic monitoring. In both cases, a marked elevation of V-wave in pulmonary capillary wedge pressure (PCWP) was shown, and a moderate-to-severe functional mitral regurgitation was observed. IABP and CRT resulted in a significant acute improvement in aortic pressure, PCWP, and V-wave amplitude compared with baseline measurements and IABP alone. These results provide a basis for studies examining the haemodynamic effects of IABP support associated with CRT in patients with heart failure refractory to medical therapy.