ANMCO Research Center Activities 2008


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ANMCO Research Center Activities 2008

  1. 1. ANMCO Research Center Activities 2008
  2. 2. ANMCO Research Center Certified UNI EN ISO 9001:2000 STORY ANMCO is the Italian Association of Hospital In 1998 ANMCO founded the Heart Care Cardiologists, a no-profit professional association of Foundation (HCF), legally recognized by the Ministry over 4100 Italian Cardiologists operating within the of Health on September 2000. HCF is registered in National Health Service. Founded in 1963, ANMCO the ONLUS registry. is dedicated to promote optimal care, prevention The aim of the foundation is to provide citizens with and rehabilitation of cardiovascular diseases a correct information on cardiovascular diseases and through organization’s proposals, clinical research, to support scientific research in the cardiovascular professional education and CME programs. field. ANMCO Research Center activities passed It also has a key role in the development and therefore to HCF. implementation of standards and guidelines for The ANMCO Research Center of HCF has received cardiological clinical practice in Italy. on December 22, 2005 the certification UNI EN In 1992 ANMCO created the ANMCO Research ISO 9001:2000 for the planning, development, Center, responsible for planning and conducting the management and coordination of research scientific and cultural projects of the Association. projects in the biomedical field. TEAM Statisticians Director Data Managers Donata Lucci Aldo P. Maggioni Marco Gorini Lucio Gonzini Giampietro Orsini Daniele Dall’Osso Regulatory and the staff of the ANMCO Administration Statistic Consultant Research Center Andrea Lorimer Renato Urso Paola Priami Laura Costanzo Fabiana Serafini Medical Consultants Secretariat Monitoring Gianna Fabbri Barbara Bartolomei Mecatti Martina Ceseri Angela Franchi Laura Sarti Francesca Bianchini Francesco Orso Ilaria Cangioli Chiara Pierattini Irina Suliman Elisa Bianchini Laura Cintelli Beatrice Del Taglia Laura Cipressa Gianluca Grilli Maria Lucia Cipressa Filippo Bambi Silvia Cabiddu Antonio Atzori ◆ 12 external clinical monitors The ANMCO Research Center is ◆ 4131 Cardiologists NETWORK coordinating a clinical Network of: ◆ 880 Cardiology Centers ◆ 44 Diabetology Centers ◆ 80 Internal Medicine Divisions This large network of centers, involved in co-operative activities, offers the possibility to conduct large observational or controlled studies enrolling patients of real world clinical practice where they are routinely treated. In this way, research and clinical practice finish to coincide, offering an incredible opportunity to optimize the quality of patient care. Such a big network gives also the possibility to translate the research results directly to clinical practice narrowing the gap between scientific knowledge and patient care.
  3. 3. ANMCO Research Center Certified UNI EN ISO 9001:2000 ACTIVITIES • Evaluation of clinical epidemiology of cardiovascular diseases in Italy • Use of resources and evaluation of their appropriateness • Diagnostic and therapeutic approaches for major cardiovascular diseases • Management of clinical trials and outcome research studies The Staff, the clinical network and the long term expertise in the cardiology field give ANMCO Research Center the possibility to manage each aspect of a clinical trial such as: ◆ Planning and preparing study protocols ◆ Clinical monitoring ◆ Managing regulatory and administrative ◆ Clinical helpline aspects of clinical trials ◆ Clinical events adjudication ◆ Safety surveillance ◆ Data management ◆ Medical communication (study material, ◆ Statistical analysis newsletter, etc.) ◆ Publications The ANMCO Research Center possesses all the tools required to manage clinical studies focused on crucial clinical questions that can lead to results with a significant impact on the clinical practice. The conduction of the research is continuously monitored by a group of clinical monitors trained in- house and co-ordinated by ANMCO Research Center. The group has a central function: it is the guarantee of a careful and appropriate management of the trial and assists and helps researchers in the management of study procedures, as established by the Good Clinical Practice rules. COLLABORATION ANMCO Research Center collaborates with Research is the promoter of the GISSI Studies independent institutions such as US National since the very beginning. In this context the Institute of Health, the Italian Ministry of Health ANMCO Research Center is serving as or the European Society of Cardiology, fully Coordinating Center for two current GISSI proj- managing a study or just co-ordinating the ects (GISSI Heart Failure and GISSI Atrial Italian Network. Fibrillation). Due to the consolidated network of cardiology The identification of real clinical problems, the centers and the expertise in managing research organization of studies aimed to clarify or solve activities, the ANMCO Research Center also co- some of these problems, the network of the cen- ordinated the Italian component of multination- ters, well representing real clinical practice, the al large-scale clinical trials planned by pharma- expertise of the staff in managing trials, the full ceutical companies. independence in conducting and interpreting results, the quick transferability of the study GISSI Studies results to clinical practice contributed to plan ANMCO together with the “Mario and implement appropriate health policies for Negri” Institute for Pharmacological the management of cardiovascular diseases.
  4. 4. PROJECT REVIEW The ANMCO working groups or any member of the A pharmaceutical or device company can support Association can propose a project of research. Each the approved projects of research. In any case, the proposed research project is evaluated by a scientif- property of the database and the right to publish ic committee nominated by the ANMCO board, the results remain by contract in the hands of the which provides an expert opinion about the scien- Foundation, assuring the full independence of the tific plausibility of the study. Then, the Research projects. Center verifies the feasibility of the proposal, defines The ANMCO Research Center has the full responsi- the costs and guarantees the technical and scientif- bility of the conduction of most of the studies ic accuracy of study management. approved by the ANMCO board. SELECTED REFERENCES OF YEAR 2007 Staszewsky L, Wond M, Masson S, Barlera S, Carretta E, Latini R, Masson S, Anand IS, Missov E, Carlson M, Vago T, Maggioni AP, Anand IS, Cohn JN, Tognoni G, Latini R, for the Angelici L, Barlera S, Parrinello G, Maggioni AP, Tognoni G, Cohn Valsartan Heart Failure Trial Investigators. Clinical, neurohor- JN and for the Val-HeFT Investigators. Prognostic value of very low monal, and inflammatory markers and overall prognostic role plasma concentrations of troponin T in patients with stable chron- of chronic obstructive pulmonary disease in patients with heart ic heart failure. Circulation 2007; 116: 1242-1249. failure: data from the Val-HeFT heart failure trial. J Card Fail Mozzafarian D, Anker SD, Anand I, Linker DT, Sullivan MD, 2007; 13: 797-804 Cleland JGF, Carson PE, Maggioni AP, Mann DL, Pitt B, Poole- Silletta MG, Marfisi RM, Levantesi G, Boccanelli A, Chieffo C, Wilson P, Levy WC. Prediction of mode of death in heart failure. Franzosi MG, Geraci E, Maggioni AP, Nicolosi GL, Schweiger C, The Seattle Heart Failure Model. Circulation 2007; 116: Tavazzi L, Tognoni G, Marchioli R on behalf of the GISSI- 392-398 Prevenzione Investigators. Coffee consumption and risk of car- Torp-Pedersen C, Caterson I, Coutinho W, Finer N, Van Gaal L, diovascular events after acute myocardial infarction. Results Maggioni A, Sharma A, Brisco W, Deaton R, Shepherd G, James from the GISSI (Gruppo Italiano per lo Studio sulla P on the behalf of the SCOUT Investigators. Cardiovascular Sopravvivenza nell’Infarto miocardico)-Prevenzione Trial. responses to weight management and sibutramine in high-risk Circulation 2007; 116: 2944-2951 subjects: an analysis from the SCOUT trial. Eur Heart J 2007; Colombo GL, Caruggi M, Ottolini C, Maggioni AP. 28: 2915-2923 Candesartan in heart failure: Assessment of reduction in mor- Casella G, Di Pasquale G, Tavazzi L, Maggioni AP. La frequenza tality and morbidity (CHARM) and resource utilization and cardiaca come obiettivo terapeutico dell’angina stabile. Ruolo costs in Italy. Vascular Health and Risk Management delle terapie attuali e loro sottoutilizzo in Italia. G Ital Cardiol 2008; 4(1): 1-12 2007; 8: 207-214. Marchioli R, Marfisi RM, Borrelli G, Chieffo C, Franzosi MG, Fabbri G, Gorini M, Maggioni AP, Di Lenarda A. Come è cambia- Levantesi G, Maggioni AP, Nicolosi GL, Scarano M, Silletta MG, ta la terapia farmacologica nel registro IN-CHF dal 1995 al 2005. Schweiger C, Tavazzi L, Tognoni G. Efficacy of n-3 polyunsatu- G Ital Cardiol 2007; 8(2): 102-106 rated fatty acids according to clinical characteristics of patients with recent myocardial infarction: insights from the GISSI- Gheorghiade M, Konstam MA, Burnett JC Jr, Grinfeld L, Maggioni Prevenzione trial. J Cardiovasc Med 2007; 8(suppl 1): AP, Swedberg K, Udelson JE, Zannad F, Cook T, Ouyang J, Zimmer S34-37. C, Orlandi C; Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators. Short- Verdecchia P, Reboldi G, Angeli F, Avanzini F, de Simone G, term clinical effects of tolvaptan, an oral vasopressin antagonist, in Pede S, Perticone F, Schillaci G, Vanuzzo D, Maggioni AP, patients hospitalized for heart failure: the EVEREST Clinical Status HEART survey study group. Prognostic value of serial electro- Trials. JAMA 2007; 297: 1332-1343. cardiographic voltage and repolarization changes in essential hypertension: the HEART Survey study. Am J Hypertens Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni 2007; 20: 997-1004 AP, Swedberg K, Udelson JE, Zannad F, Cook T, Ouyang J, Zimmer C, Orlandi C; Efficacy of Vasopressin Antagonism in Fabbri G, Gorini M, Maggioni AP, Oliva F. Scompenso cardia- Heart Failure Outcome Study With Tolvaptan (EVEREST) co: pazienti critici. G Ital Cardiol 2007; 8(9): 568-573 Investigators. Effects of oral tolvaptan in patients hospitalized for Fabbri G, Gorini M, Maggioni AP, Oliva F. Scompenso cardia- worsening heart failure: the EVEREST Outcome Trial. JAMA co: l’importanza della continuità assistenziale. G Ital Cardiol 2007; 297: 1319-1331. 2007; 8(6): 353-358 Zannad F, Huvelle E, Dickstein K, van Veldhuisen DJ, Stellbrink C, Køber L, Cazeau S, Ritter P, Maggioni AP, Ferrari R, Lechat P. Left Boccanelli A, Cacciatore G, Mureddu GF, de Simone G, bundle branch block as a risk factor for progression to heart fail- Clemenza F, De Maria R, Di Lenarda A, Gavazzi A, Latini R, ure. Eur J Heart Fail 2007; 9: 7-14 Masson S, Porcu M, Vanasia M, Gonzini L, Maggioni AP, on behalf of the AREA IN-CHF Investigators. Baseline characteris- Krum H, Latini R, Maggioni AP, Anand I, Masson S, Carretta E, tics of patients recruited in the AREA IN-CHF study Ingrillì F, Pettinati G, Glazer R, Tognoni G, Cohn J. Statins and (Antiremodelling Effect of Aldosterone Receptors Blockade symptomatic chronic systolic heart failure: a post-hoc analysis with Canrenone in Mild Chronic Heart Failure). J Cardiovasc of 5010 patients enrolled in Val-HeFT. Int J Cardiol 2007; Med (Hagerstown) 2007; 8: 683-691 119: 48-53
  5. 5. IN-HF Italian Network on Heart Failure Working Group: Heart Failure STUDY PARTIALLY SUPPORTED BY NOVARTIS BACKGROUND AND RATIONALE A registry able to capture all the relevant clinical information of patients Chronic Heart Failure (CHF) is associated with a high burden of mortali- with HF including their acute episodes of decompensation could ty and morbidity, reduced quality of life and increasing healthcare costs improve our knowledge on epidemiology and outcomes of real world in both US and Europe. Evidence-based medicine represents the most patients with this clinical condition. effective mean of ensuring that patients receive high-quality care and appropriate pharmacological/non-pharmacological management. MAIN OBJECTIVES With the increased prevalence of CHF there is a concomitant increase in To provide the Italian Cardiology Units with an ad-hoc electronic system the number of related hospitalizations and, as CHF progresses, the risk for the collection of clinical epidemiological variables of patients with of acute exacerbation increases. Acute Heart Failure (AHF) is a complex, acute and chronic HF. heterogenous, clinical syndrome characterized by a rapid onset of signs A large network of centers dedicated to the treatment of patients with and symptoms secondary to abnormal cardiac function, and it is often HF will allow a reliable description of: life threatening, requiring urgent therapy. • clinical epidemiology of patients with HF In the United States, a primary diagnosis of AHF accounts for more than • prescription patterns one million hospitalizations each year, with similar numbers suggested • epidemiology of the diagnostic/therapeutic strategies for Europe. Despite significant advances in diagnosis and therapy, • postmarketing surveillance patients with AHF continue to have a poor long-term prognosis. Clinical • prognostic score evaluation destabilizations leading to hospitalization are associated with haemody- • cost analysis namic and neuro-hormonal alterations which can contribute to progres- sive ventricular dysfunction and dilation, mitral regurgitation, increased • subgroups of patients of specific clinical interest wall stress, and progressive myocyte loss as a result of apoptosis and • reference data for clinical trial design. necrosis. Registries and surveys have been conducted in patients with either CHF STUDY DESIGN AND RECRUITING CENTERS or AHF but a description of the whole clinical story of patients with HF Permanent, multicentric, prospective, observational registry. including the acute episodes and the consequent changes in clinical All the Italian centers interested in the treatment of patients with HF can conditions and in the management strategies are not available. participate in data collection. IN-HF OUTCOME Italian Registry on Heart Failure (IN-HF) Outcome IN-HF Outcome Steering Committee: L. Tavazzi (Chairman), G. Cacciatore, A. Chinaglia, A. Di Lenarda, A.P. Maggioni, M. Metra, A. Mortara, F. Oliva, M. Senni STUDY PARTIALLY SUPPORTED BY NOVARTIS, MEDTRONIC AND ABBOTT STUDY DESIGN Subgroup of patients with hypertension: approximately 1300-1800 Prospective, non-interventional, multicentric observational study in patients. patients with chronic (CHF) and acute heart failure (AHF). Subgroup of patients with implanted devices: approximately 325-550 patients. MAIN STUDY OBJECTIVES Subgroup of patients admitted for AHF treated with IV inotropes or vasodilators: approximately 1500 patients. To describe the demographic, clinical, and biological characteristics of Patients will be included by approximately 70 Italian Cardiology Centers. patients with CHF and AHF followed by a setting of Italian cardiology centers. To describe the diagnostic and pharmacological/non pharmacological STUDY ADVANCEMENT (as of May 5, 2008) therapeutic approaches undertaken in the routine practice of cardiologists in following out-patients with CHF and during the hospital phase for AHF. Study enrollment started on November 2007 To assess the in-hospital and out-of-hospital outcome of patients with CHF Participating centers: 82 and the prognostic predictors of this outcome. Activated centers: 34 Recruiting centers: 10 STUDY POPULATION Enrolled patients: 225 Outpatients with CHF diagnosed according to the ESC guidelines. Pts with acute heart failure 7 Patients admitted for AHF and treated with IV therapy. Subpopulations of HF patients will be specifically focused with larger and more detailed data Pts with chronic heart failure 218 collection: TOP TEN • Patients with HF in whom ICD, CRT or both are implanted during the course of the study. Center N. of pts • Patients admitted for AHF with a story of hypertension and a SBP >160 Roma, Ospedale S. Giovanni, U.O. Cardiologia 188 mmHg. • Patients admitted for AHF and treated with IV inotropic agents or Ascoli Piceno, Osp. Gen.le Prov.le, Divisione di Cardiologia 53 vasodilators. Albano Laziale, Osp. Riuniti Albano-Genzano, U.O.C. di Cardiologia 25 ENROLLMENT AND FOLLOW-UP PERIOD Passirana-Rho, Presidio Ospedaliero,Divisione di Cardiologia 19 The enrollment will last twelve month. Each included patients will be fol- lowed up for 1 year. Patients with CHF and patients with AHF treated with Lumezzane, Fondazione Salvatore Maugeri, U.O. di Cardiol. Riabil. 16 IV inotropes or vasodilators and those admitted for hypertensive HF will be followed-up at 3, 6 and 12 months. Napoli, Ospedale Incurabili, Divisione di Medicina 14 Firenze, Nuovo Ospedale San Giovanni di Dio, U.O. Cardiologia 12 SAMPLE SIZE A formal sample size was not calculated. With respect to the different cat- Firenze, Az. Ospedaliero-Universitaria, Cardiologia Generale 1 10 egories of patients the expectations in terms of numeros- San Pietro Vernotico, Ospedale N. Melli, U.O. Semplice Cardiologia 8 ity are reported below: CHF: approximately 2500-3500 patients. Brescia, Spedali Civili, Divisione di Cardiologia 7 AHF: approximately 2500-3000 patients.
  6. 6. GISSI-HF A large scale clinical trial testing the effects of n-3 PUFA and statins on mortality/morbidity of patients with symptomatic chronic Heart Failure Steering Committee: L. Tavazzi (Chairman), G. Tognoni (Co-Chairman) M.G. Franzosi, R. Latini, A.P. Maggioni, R. Marchioli, G.L. Nicolosi, M. Porcu STUDY PARTIALLY SUPPORTED BY PFIZER, SPA, SIGMA TAU FOR THE N-3 PUFA HYPOTHESIS AND BY ASTRAZENECA FOR THE STATIN HYPOTHESIS In collaboration with Mario Negri Institute, Milan, Italy and Consorzio Mario Negri Sud, S. Maria Imbaro, Italy BACKGROUND - any condition that in the opinion of the investi- NUMBER OF PATIENTS TO BE RECRUITED While pharmacological treatments specifically tar- gator would jeopardize the evaluation of effica- Since the trial is event driven, the number of geted to the cardio-circulatory system have been cy or safety or be associated with poor adher- ence to the protocol; expected deaths which are needed to allow a reli- largely investigated, scanty controlled data are able evaluation of the efficacy of tested drugs is set available concerning the role of dietary and meta- - presence of any non-cardiac disease (e.g. can- cer) that is likely to significantly shorten life for both R1 and R2 at 1252 for a study power of bolic approaches in the management/outcome of 90% at the significance level α=0.045. patients with heart failure. A large scale, random- expectancy; - treatment with any investigational agent within Patients enrolled in each trial will be followed until ized, clinical trial is proposed to test the effects of (a) n-3 PUFA and (b) a lipid lowering agent on top of 1 month before randomization; the occurrence of a sufficient number of deaths in R2 the best recommended treatments for heart failure. - patients already on treatment with n-3 PUFA or unless the trial is stopped early on the basis either of statin for whom the prescription is confirmed. the interim analysis or of new scientific evidences. STUDY DESIGN R2 (statin hypothesis): EXCLUSION CRITERIA FOR All primary end points will be validated centrally The GISSI-HF is a prospective, multicenter, random- - current serum creatinine level >2.5 mg/dL; by an ad-hoc committee (E. Geraci, M. Scherillo, ized, double blind, placebo controlled study, with - current ALT, AST level >1.5 times the upper nor- D. Bertoli, F. Cobelli, C. Fresco, A. Ledda, G. Levan- randomized allocation of patients with a clinical mal limit; tesi, C. Opasich, F. Rusconi, G. Sinagra, F. Turazza, diagnosis of heart failure. - current CPK upper normal limits. A. Volpi). GISSI-HF SUBPROJECTS Final satus on substudies Active Pts with at Substudy least 1 exam centers (number, % of target) Echo (S. Ghio) 33 628 (84%) Blood (R. Latini, S. Masson) 54 1233 (154%) Genetic (M.G. Franzosi, L. Crociati) 116 2300 (115%) OBJECTIVES OF THE STUDY Holter (M.T. La Rovere) 42 432 (58%) PRIMARY OBJECTIVES Exercise (U. Corrà) 9 86 (22%) • All-cause mortality • All-cause mortality or hospitalizations for cardio- Quality of life (P. Di Giulio) 83 1573 (79%) vascular reasons OTHER END-POINT MEASURES OF EFFICACY Microalbuminuria (R. Latini, S. Masson) 76 2529 (101%) • Cardiovascular mortality • Cardiovascular mortality or hospitalizations for any reason STUDY ADVANCEMENT (as of May 2, 2007) • Sudden cardiac death Participating Centres: 356 Patient Enrolled: 6975 • Hospitalizations for any reason Enrollment: August 2002-February 2005 • Hospitalizations for cardiovascular reasons • Hospitalizations for congestive heart failure R1 (n-3 PUFA vs Placebo) R2 (Rosuvastatine vs Placebo) • Myocardial infarction Males 5459 (78.3%) 3542 (77.4%) • Stroke ENTRY CRITERIA Age (mean±SD) yrs 67.2±10.7 (range 18-97) 67.6±10.8 (range 18-97) • Clinical evidence of heart failure according to >70 yrs 2964 (42.5%) 2026 (44.3%) the ESC guidelines (NYHA class II-IV) • Any left ventricular EF measured within 3 months NYHA II 4424 (63.4%) 2859 (62.5%) from enrolment (if EF >40%, at least 1 hospital admission for HF in the previous year) NYHA III 2365 (33.9%) 1599 (35.0%) • No age limits NYHA IV 185 (2.7%) 115 (2.5%) • Any etiology • Informed consent CHD etiology 3467 (49.7%) 1828 (40.0%) COMMON EXCLUSION CRITERIA (R1=n-3 PUFA vs placebo and R2=rosuvastatin vs placebo): EF% (mean±SD) 33.1±8.5 (range 10-87) 33.2±8.7 (range 10-87) - AMI, unstable angina or revascularization proce- >40% 654 (9.4%) 461 (10.1%) dure within 1 month; - planned cardiac surgery, expected to be per- formed within 3 months; TOTAL DEATHS - congenital or primary valvular etiology; - known hypersensitivity to study treatments; R1 R2 - significant liver disease; 1964/6975 (28.2%) 1297/4574 (28.4%) - pregnant or lactating women or women of childbearing potential not protected from preg- nancy by an accepted method of contraception; Final results will be presented at the next ESC Congress in Munich (August 30 - September 3, 2008)
  7. 7. CENSUS OF THE CARDIOLOGY CENTERS OF THE ITALIAN NATIONAL HEALTH SERVICE STUDY ENDORSED BY THE ITALIAN FEDERATION OF CARDIOLOGY (FIC) In collaboration with the Italian Society of Cardiology (SIC) PARTIALLY SUPPORTED BY MERCK SHARP & DOHME AIMS ♥ Describe the distribution of Italian Cardiology Centers. The survey included: - University centers - Hospital centers - Private hospital centers with beds ope- simple (echo, stress test, Holter) and more Cardiosurgery together. In Table 1 the number rating within the Italian National complex (stress echo, transesophageal of hospital with cardiology center and Nuclear Health Service echo, transesophageal electrophisiology). Medicine and with Electrophysiology facilities ♥ Describe the organization, the activities is also reported. and the services provided by each cardiolo- METHODS gy center in the year 2005. The number of CCUs and CCUs beds/popula- On March 2006 a letter was sent to the heads Qualitative and quantitative data have tion overall in Italy (1 CCU/136577 and 1 CCU of the 843 Italian Cardiology centers infor- been collected in terms of: bed 1/21816) and in the 21 Italian regions are ming them of the interest for a new census - Number and territorial distribution of reported in Figure 2. The historical gap survey based on the data of year 2005. Coronary Care Units (CCU) between North and South is no more present. Each center received a user name and a pas- - Cardiology beds: sword to enter the data of the census using a The number of physicians operating in the - CCU beds WEB based system. 773 centers who replied to this questionnaire - Other cardiology beds is 6915. The mean number of physicians oper- R E S U LT S - Cardiac catheterization laboratories ating in Hospital, University and Private cen- (with/without interventional section) The rate of reply was 92% (773/843 Centers: ters and in any different type of cardiology - Electrophysiology laboratories 93% Hospital; 89% University and 84% centers is reported in Figure 3. The mean Private Hospital) and provides a complete pic- number varies in relation to the complexity of - Nuclear cardiology laboratories ture of the cardiology network in the Italian the centers ranging from 3.65 physicians for - Specific outpatients cardiology clinics: Health Service (Figure 1). - Pace maker the centers without beds to 15.44 physicians - Hypertension for the centers with CCU and Cath Lab. There is a cardiology center in 728 (48%) out - Heart Failure of 1503 Italian hospitals. Out of these 728 - Pediatry hospital 55% have CCU, 32% a Cath Lab Rate of reply - Epidemiology and prevention (90% with PCI facility). There are 83 (11%) ♥ Describe the type of routine non invasive hospitals with Cardiosurgery. In 70 hospitals examinations performed in each center: (10%) there are CCU, Cath Lab and Hospitals with cardiology centers Table 1 Figure 1 Inhabitants / CCU bed Mean number of physicians in the cardiology centers P VA L BZ TN V F LG ER North TO U MR LZ A Center MO CM PG B CL SI SA South Italy Figure 2 Figure 3
  8. 8. BLITZ 3 Epidemiology of the hospitalizations in the Italian Coronary Care Unit network Working Group on Emergency/Urgency Steering Committee: L. Oltrona Visconti (Chairman), F. Chiarella, M. Cassin, A. Chinaglia, S. Pirelli, G. Scorcu, G. Casella, M.R. Conte, G. Fradella STUDY PARTIALLY SUPPORTED BY NOVARTIS, BOEHRINGER-INGELHEIM, SANOFI-AVENTIS RATIONALE term outcome, the prevalence of the most important co-mor- The current worldwide scientific cardiology community shares a bidities (diabetes, kidney failure, broncho-pulmonary obstructive consensual opinion on the relevance of prospective registries, disease) and furthermore, the implications in terms of resource due to the reliable description of the epidemiological profile and absorption. The diagnostic procedures and therapeutic options therapeutic management of the patients of real clinical practice, have been registered in a case-report web-based form. that randomized trials generally do not appropriately represent. On the same time, the role of the Intensive Heart Care Unit INCLUSION CRITERIA (IHCU) has changed: nowadays various cardiovascular patholo- All patients admitted in the participating IHCU from April 7 to gies like cardiogenic shock, acute heart failure, arrhythmias, pul- 20, 2008. monary embolism, myocarditis, post-coronary angiography fol- low-up added to acute coronary syndromes, but precise preva- lence is still unknown. There is also no evidence regarding the EXCLUSION CRITERIA admission rate, the most frequent diagnosis, the patients-flow Only the patients who refused their written informed consent between Department Emergency Admission (DEA), 118 and were excluded. IHCU, the follow-up in other units or other hospitals. THERAPEUTIC OPTIONS OBJECTIVES AND METHODS Being fully observational, the study did foresee neither specific The present study as the aim to describe the epidemiological pharmacological/non-pharmacological treatments nor specific profile of the current admission in the IHCU, the main aspects of invasive/non invasive diagnostic procedures, but the patients’ the clinical patients’ management including “the road map” management was left to the decisions of the enrolling cardiol- after the acute phase (transfer to other Departments), the short- ogists. PRELIMINARY RESULTS 6986 consecutive admissions were registered by 332 Italian IHCUs, well representing the existing IHCUs in Italy. Italian IHCU Participating Italian IHCU Where patients are coming from? n. n. (%) Transfer with 118: 25.8% Italy 409 332 (81%) North 169 135 (80%) Center 97 77 (79%) South 143 120 (84%) Type of hospital Only IHCU 205 162 (79%) IHCU and Cath Lab 124 105 (85%) IHCU and Cath Lab ■ Emergency room/DEA ■ Other hospital and Heart Surgery Unit 80 65 (81%) ■ Directly from outside the hospital to IHCU with 118 ■ Cardiology ward ■ Other department of the same hospital Baseline Characteristics Females 36.3% Length of stay in IHCU (days) Age >75 years 38.9% Age (mean±SD), years 70±13 All admissions median [25%, 75%] 4 [2, 5] All-cause mortality in IHCU 3.3% Patients with STEMI median [25%, 75%] 4 [3, 5] Most frequent diagnosis at discharge from IHCU Patients with NSTEMI/Unstable Angina STEMI 21.4% median [25%, 75%] 4 [3, 6] NSTEMI/Unstable Angina 30.7% Patients with Heart Failure Heart Failure 13.1% median [25%, 75%] 4 [3, 6]
  9. 9. GISSI-AF Randomized, prospective, multicenter study on the use of an angiotensin II AT1-receptor blocker in the prevention of Atrial Fibrillation recurrence Steering Committee: M. Disertori (Chairman), R. Latini (Co-Chairman), A.P. Maggioni, P. Delise, G. Di Pasquale, M.G. Franzosi, L. Staszewsky, G. Tognoni STUDY PARTIALLY SUPPORTED BY NOVARTIS In collaboration with Mario Negri Institute, Milan BACKGROUND STUDY DESIGN The possibility to prevent atrial fibrillation (AF) recurrence with antiar- rhythmic agents is very limited, given the discouraging results obtained with current drugs in many patients. Data from experimental studies suggest that angiotensin II AT1-receptor blockers (ARBs) can influence atrial remodeling, a key factor in AF initiation and maintenance. Moreover, some preliminary clinical data show that ARBs can prevent AF episodes. GISSI-AF is a randomized, prospective, parallel group, placebo- controlled, multicenter study designed to test whether ARBs can reduce AF recurrence. OBJECTIVES AND METHODS Primary objective of the study is to demonstrate that, in patients with his- tory of recent AF treated with the best recommended therapies, the addi- tion of the ARBs valsartan (titrated up to 320 mg) is superior to placebo in reducing: 1. first recurrence of AF, 2. rate of patients with more than one AF episode, over the whole follow-up. A substudy will analyse the effect of valsartan on left atrial dimensions and on neurohormones. NUMBER OF PATIENTS TO BE RECRUITED The study population will consist of patients with symptomatic AF (at least 2 ECG documented AF episodes in the previous 6 months or suc- The GISSI-AF is the largest trial ever conducted aimed at assessing the cessful cardioversion in the last 2 weeks) and having underlying cardio- role of ARBs in reducing recurrence of AF. vascular diseases or comorbidities. The patients will be randomized in a The sample size has been calculated with the following assumptions: AF 1:1 ratio to receive valsartan or placebo. The patients will be followed for recurrence over 1 year of follow-up in the control group= 50%, relative 12 months from study entry. reduction of AF recurrence with valsartan =17.6 % (from 50% to 41.2 %), with 88% power and a 2 error of 0.04. A total of 1402 patients (701 in each arm) will be randomized in a 1:1 ratio to receive either val- INCLUSION CRITERIA sartan or placebo on top of the existing treatments. 1. Male and female patients with at least 40 years of age, 2. In sinus rhythm at randomization (for at least 48 h in case of electric STUDY ADVANCEMENT (as of May 5, 2008) or pharmacologic cardioversion), 3. At least two ECG documented episodes of symptomatic AF in the pre- Randomization closed on January 14, 2007 vious 6 months, Follow up period closed December 31, 2007 or Recruiting centres: 114 Patients enrolled: 1442 Successful cardioversion for AF between 14 days and 48 hours before randomization, CHARACTERISTICS OF ENROLLED PATIENTS (n. 1442) 4. At least one of the following: a) HF or documented history of LV dysfunction (defined as an EF Female 37.7% <40%), b) History of hypertension 6 months with or without LVH, Age mean (mean±DS) years 67.8±9.2 (range 40-92) c) Type II diabetes mellitus, d) Documented history of stroke or peripheral vascular disease, Age >70 years 44.5% e) Documented history of coronary artery disease, f) Lone AF with documented LA dilation (LA diameter 45 mm for At least 2 episodes of AF in the last 6 months 24.2% men and 40 mm for women). Both criteria: 15.4% 5. Informed consent. CVE in the last 2 weeks 60.4% EXCLUSION CRITERIA QUALITY SCORE TOP TEN 1. Need for a continuous treatment with ARBs for any clinical reason, 2. Contraindications or known hypersensitivity to ARBs, Quality Hospitals 3. Persistent standing systolic blood pressure <110 mmHg, Score 4. Recent (<6 weeks) acute myocardial infarction or bypass surgery, or percutaneous coronary intervention, Bergamo, USC Cardiologia, Ospedali Riuniti 10.0 5. Clinically significant valvular etiologies, 6. Thyroid dysfunction, San Bonifacio, UOC Cardiologia, Ospedale G. Fracastoro 10.0 7. Indication for pacemaker or ICD implant or for an ablative treatment, Terni, UO Cardiologia Territoriale, Azienda USL 4 Terni 10.0 8. Planned cardiac surgery, expected to be performed within 3 months, 9. Serum creatinine level above 2.5 mg/dL, San Daniele del Friuli, UOS Cardiologia, Ospedale S. Antonio 9.7 10. Significant liver disease, 11. Pregnant or lactating women or women of childbearing potential Roma, Divisione di Cardiologia e UTIC, Osp. S. Filippo Neri 9.7 who are not protected from pregnancy by an accepted method of contraception, Cosenza, Divisione di Cardiologia, Ospedale SS. Annunziata 9.7 12. Any condition that in the opinion of the investigator would jeopard- ize the evaluation of efficacy or safety or be associated with poor Catania, UOC di Cardiologia, Ospedale Garibaldi-Nesima 9.7 adherence to the protocol, 13. Presence of any non-cardiac disease (e.g. cancer) that is likely to sig- Milazzo, Servizio di Cardiologia, Pres. Ospedaliero ‘G. Fogliani’ 9.7 nificantly shorten life expectancy, Cles, Medicina Interna, Ospedale di Cles 9.7 14. Treatment with any investigational agent within 1 month before randomization, Bari, UO di Cardiologia Ospedaliera, Osp. Consorziale Policlinico 9.5 15. Currently decompensated HF.
  10. 10. Cardio-Sis Italian Study on the Cardiovascular Effect of Systolic Blood Pressure Control Working Group: Prevention Steering Committee: P. Verdecchia (Chairman), J.A. Staessen, A. Achilli, G. De Simone, A. Ganau, G. Mureddu, S. Pede STUDY PARTIALLY SUPPORTED BY BOEHRINGER-INGELHEIM, PFIZER, SANOFI-AVENTIS In collaboration with the Associazione Umbria Cuore e Ipertensione (AUCI) RATIONALE composite pool of major cardiovascular events. 5) Causes precluding ECG interpretation for LVH: com- Only a minority of treated hypertensive subjects achieve 7. To assess the distribution of the different treatments plete right or left bundle block, Wolff-Parkinson- adequate BP control. Unfortunately, poor control of BP at any visit, both in the total population and in spe- White syndrome, previous Q-wave myocardial during treatment predicts a high risk of future cardio- cific subgroups (defined by sex, age, etc). infarction. vascular disease. There is growing evidence that ECG Comparisons between different treatments will not 6) Any disease causing reduced life expectancy. changes in LVH during treatment are potent predictors be allowed because treatments are not given accord- 7) Unwilling to participate. of outcome. In the Framingham Heart Study, subjects ing to a randomised sequence and therefore an allo- 8) Significant valvular heart disease. with baseline LVH and serial increase over time in the cation bias would be most likely to occur. TREATMENT ECG voltages were twice as likely to suffer a cardiovas- INCLUSION CRITERIA Antihypertensive therapy will be administered in an cular event over the subsequent years when compared To be eligible, patients must meet all the following criteria: open fashion and tailored to the single subject accord- with those with a decrease in the voltages. 1. Written informed consent to the study. ing to individual risk profile defined by concomitant risk There is no evidence from prospective, randomised, 2. Age 55 years at randomisation. There is no upper factors and diseases, in line with current guidelines. controlled studies that a therapeutic strategy aimed to age limit. Pharmacologic and non pharmacologic treatment of achieve a tighter control of systolic BP (for example: 3. Clinic blood pressure 150 systolic in 2 visits at dis- lipid disorders will also be guided by individual risk pro- < 130 mmHg) will result in a greater reduction in LVH tance of 7-14 days, irrespective of diastolic pressure. file, according to current guidelines. Achievement of than a usual strategy (systolic BP reduction < 140 Duration of treatment before visit 1 must be at least adequate BP control may require adjunct of further mmHg). 12 weeks. drugs to those already taken by patients. STUDY OBJECTIVE 4. At least one additional risk factor including the fol- Thus, treatment will include different combinations of Aim of the study is to ascertain whether an intensive lowing: prior drugs (background therapy) and dispensed drugs. treatment strategy finalized to decrease office systolic 4.1. Current cigarette smoking. In order to well define applicability of results of the BP < 130 mmHg is superior to the usual strategy 4.2. Total cholesterol 200 mg/dl, or HDL choles- study to the clinical practice, the use of specific antihy- focused on lowering systolic BP < 140 mmHg in hyper- terol < 40 mg/dl, or LDL cholesterol 130 pertensive drugs which will be dispensed for the pur- tensive subjects aged ≥ 55 years and poorly controlled mg/dl. pose of this study will be restricted according to the fol- (office systolic BP 150 mmHg), in terms of favourable 4.3. Family history of cardiovascular disease in male lowing list: change in ECG criteria for LVH. Patients with concomi- first degree relative < 55 years or female first - Diuretics: hydrochlorothiazide (in fixed combination tant diabetes or renal failure will be excluded from this degree relative < 65 years. with ramipril or telmisartan), furosemide [25 mg]. 4.4. Previous TIA or stroke. - Beta-blockers: bisoprolol [10 mg]. study because achievement of a tight BP control in 4.5. Previous coronary artery disease defined by evi- - ACE-inhibitors: ramipril (alone [5 and 10 mg] or in these patients is already supported by existing evidence. dence of: fixed combination with hydrochlorothiazide [ramipril LVH at ECG will be assessed by the Perugia score. 4.5.1. Documented myocardial ischemia by 5 mg + hydrochlorothiazide 25 mg]). The primary end-point for the comparison between the ECG, stress-echocardiography or scintig- - Angiotensin II receptor antagonists: telmisartan (alone two groups will be the change in LVH at ECG. raphy, or Secondary end-points: [80 mg] or in fixed combination with hydrochloroth- 4.5.2. Angiographic stenosis > 50% in at least 2 1. To compare the 2 groups in the time course of BP iazide [telmisartan 80 mg + hydrochlorothiazide 12.5 major epicardial vessels, or changes. mg]). 4.5.3. Prior aorto-coronary by-pass or percuta- 2. To compare the 2 groups in the primary and second- - Calcium-antagonists: amlodipine [10 mg]. neous coronary angioplasty, or ary end-points only in the subjects who achieved the 4.5.4. Non Q wave myocardial infarction. - Centrally acting sympathetic inhibiting drugs: cloni- target BP (< 140 mmHg and < 130 mmHg) (‘by pro- 4.6. History of peripheral occlusive arterial disease dine (transdermal) [2 mg]. tocol-analysis’). (claudicatio intermittens associated with angio- STUDY ADVANCEMENT (as of May 5, 2008) 3. To perform the following pre-specified sub-group graphic or ecographic evidence of > 60% steno- analyses: sis). Duration of the study: 4 years (2 years for enrollment, 3.1. Absence Vs presence of LVH at randomization. 2 years follow-up) 3.2. Age > Vs < 70 years at randomization. EXCLUSION CRITERIA Study enrollment started on February 2005 3.3. Men Vs Women. 1) Diabetes, defined by fasting glucose > 125 mg/dl in Study enrollment closed on February 2007 4. To compare the 2 groups in the continuous (Cornell 2 samples or ongoing anti-diabetic treatment. Patients expected: 1100 voltage) and non continuous (strain, Romhilt-Estes) 2) Renal failure, defined by a serum creatinine > 2.0 Activated Centers: 50 components of the Perugia score. mg/dl. Randomizing Centers: 44 5. To assess the relation between BP changes and LVH 3) Chronic atrial fibrillation or flutter. Randomized Patients: 1111 changes in the total sample and in each group. 4) Clinically significant hepatic or haematological disor- 6. To compare the two groups in the incidence of a ders, alcoholism, drug addiction. Patients who already concluded the study: 484 Baseline characteristics Randomized Patients randomized Patients randomized Patients to Usual strategy to Intensive strategy (n. 1111) (n. 553) (n. 558) Clinical and demographic variables Age (years)* 66 (7) 66 (7) 66 (7) Males (%) 41 41 41 Weight (Kg) (mean) 74 74 74 Height (cm) (mean) 163 163 163 SBP at visit 1 (mmHg)* 162 (11) 162 (11) 162 (11) DBP at visit 1 (mmHg)* 89 (9) 89 (9) 89 (9) HR at visit 1 (bpm)* 70 (10) 70 (11) 70 (10) Prevalence of risk factors Cigarette smoking (%) 21 20 21 Hypercholesterolemia (%) 75 76 74 Family history for CV disease (%) 27 28 26 Previous stroke/TIA (%) 8 8 7 Coronary artery disease (%) 11 12 10 Claudicatio intermittens (%) 2 1 3 Laboratory Examination Creatininemia (mg/dl)* 0,94 (0,23) 0,94 (0,22) 0,94 (0,23) Glycemia (mg/dl)* 97 (13) 97 (11) 97 (14) Uric acid (mg/dl)* 5,8 (4,3) 5,9 (4,9) 5,7 (3,7) Total Cholesterol (mg/dl)* 216 (42) 217 (45) 215 (39) HDL Cholesterol (mg/dl)* 57 (20) 57 (20) 57 (20) LDL Cholesterol (mg/dl)* 130 (38) 130 (40) 130 (37) Triglycerides (mg/dl)* 140 (80) 143 (88) 137 (72) Proteinuria (%) 5 6 5 * mean (± SD)
  11. 11. DYDA Left ventricular DYsfunction in DiAbetes Epidemiological survey on incidence and prevalence of left ventricular dysfunction in diabetic patients without known cardiac disease Working Groups: Heart Failure and Prevention Steering Committee: M. Comaschi (Chairman), A. Di Lenarda (Co-Chairman), P. Faggiano, C. Giorda, L. Tarantini, M. Velussi SUBSTUDY ON LEFT VENTRICULAR DYSFUNCTION IN DIABETIC PATIENTS WITH ARTERIAL HYPERTENSION G. Cioffi, G. De Simone, P. Faggiano (Coordinator), G.F. Mureddu, P. Verdecchia STUDY PARTIALLY SUPPORTED BY SANOFI-AVENTIS In collaboration with AMD (Associazione Medici Diabetologi) BACKGROUND Centre will have to enrol at least 30 patients. 40 PARTICIPATING CENTERS Diabetes is a well known risk factor for heart failure and poses an additional risk to develop left ventricular dysfunction (LVD): in the Interpretation of findings community studies, LVD have twofold higher prevalence in diabetic from instrumental examina- than non diabetic subjects. tions such as ECG, echocar- The presence of asymptomatic LVD in diabetics is frequent and is diogram, and from blood prognostically grim. samples analysis such as BNP, In the Cardiovascular Health Study, at baseline evaluation, 40% of the HbA1c, hs-CRP and microal- 1343 diabetic patients (age >65 years) had subclinical LVD and dur- buminuria at baseline and ing the follow-up of 6.4 years had higher mortality rate (relative risk after two-years of follow up 1.5) with respect to diabetic subjects without asymptomatic LVD. (only for ECG and echocar- Thus, there is the need to identify practicable and cost-effective path- diogram) will be done by a ways to screen diabetic subjects at high risk to develop LVD in order central Core Lab. to initiate an early appropriate and intensive diagnostic and thera- Registry. For seven days, peutic plan. before the beginning of the enrolment period, each dia- STUDY DESIGN betology center will keep a registry of all patients visited. Prospective, multicentric, nationwide epidemiological study. The Study duration: Two years screening and enrolment phase will last 12 months or until the enrol- for each patient enrolled. ment of 1000 patients. STUDY ADVANCEMENT (as of May 5, 2008) Enrollment 12 months 24 months Enrollment: July 2006 - March 2008 ● ➠ ● ➠ ● Participating centers: 37 Visit 1 Visit 2 Visit 1 (at entry) (12 months (24 months Enrolled patients: 970 follow-up) follow-up) The follow up period is ongoing ECHO ECHO ECG ECG Baseline characteristics of 970 enrolled patients Biohumoral sample Males 603 (62.2%) Age (mean±SD) years 62 ± 7.7 OBJECTIVES Age >70 years 144 (14.9%) Primary Objective. To evaluate in patients with type II diabetes without documented TOP TEN heart disease, the prevalence of diastolic and/or systolic left ventricu- lar dysfunction (ejection fraction 50% and/or diastolic abnormali- Center n. of pts ties) at echocardiogram at enrollment and to identify their predicting Terni, clinical, laboratory and non-invasive instrumental parameters. A.O. Santa Maria, Clinica Medica 51 Secondary Objective. Montecchio Emilia, 1) to evaluate the incidence of systolic and/or diastolic LVD at two Ospedale E. Franchini, Medicina Interna 50 years in patients with normal ventricular function at baseline, Milano, 2) to evaluate the incidence and types of ECG abnormalities at two Ospedale San Paolo, Medicina II 49 years in patients with normal ECG at baseline, Chieri, 3) to evaluate two year all-cause mortality and hospitalization for car- Ospedale Maggiore, Diabetologia 47 diovascular causes. Brescia, STUDY POPULATION Spedali Civili, U.O. Diabetologia 44 Inclusion Criteria Mirano, 1) Patients with type II diabetes (according to WHO criteria) Ospedale Civile, Medicina 44 2) No history of heart disease San Benedetto del Tronto, 3) Age > 45 years Osp. Madonna del Soccorso, Diabetologia 40 4) Written consent form Firenze, Nuovo Osp. San Giovanni di Dio, Diabetologia 40 STUDY SETTING Arenzano, The study will be performed in 40 Italian Ospedale La Colletta, U.O. Diabetologia 37 Diabetology Centres. Each Center will be associat- Prato, ed to a reference Cardiology unit where instrumen- Osp. Misericordia a Dolce, Diabetologia 35 tal cardiology evaluation will be performed. Each
  12. 12. IN-ACS OUTCOME Italian Network on Acute Coronary Sindromes Clinical epidemiology (and outcome) of patients hospitalized in Italy with acute coronary sindromes Working Group: Acute Cardiac Care IN-ACS Outcome Steering Committee: A. Boccanelli (Chairman), S. Giampaoli (Co-chairperson), L. Bolognese, F. Chiarella, G. Di Pasquale, A. Mafrici, M. Scherillo, C. Schweiger STUDY PARTIALLY SUPPORTED BY SANOFI-AVENTIS AND BRISTOL-MYERS SQUIBB In collaboration with the Istituto Superiore di Sanità STUDY DESIGN AND STUDY POPULATION Substudy IN-ACS Get Appropriate modified the most relevant current guide- The study is designed as a national, multicen- Antiplatelet therapy is the leading therapy in lines. For this reason it seemed necessary to tre, observational study. Clinical data at base patients with ACS without ST elevation develop a substudy of IN-ACS Outcome to line and during a follow-up period of one year undergoing or not to a revascularization pro- verify the rate of application of guidelines and will be collected using a web-based system. cedure. the safety profile of the different antiplatelet The study population is composed of patients, Recently several clinical trials have markedly therapies in the “real world” patients. with a diagnosis of ACS, admitted consecu- tively to cardiology and internal medicine STUDY ADVANCEMENT (as of May 5, 2008) wards participating in the study. Duration: one year of enrolment for each 41 Recruiting centers centre, one year of follow-up for each patient 32 CCUs TOP TEN (at 1, 3, 6 and 12 months). 7 internal medicine Center N° of pts 2 cardiology ward Roma, Ospedale San Giovanni 588 AIM OF THE STUDY To verify short and mid-term outcome of in- Enrolment period December 2005-February 2008 Bologna, Osp. Maggiore C.A. Pizzardi 576 patients with ACS. Patients enrolled: 5892 Arezzo, Ospedale San Donato 405 To obtain information on the management Follow up period is ongoing pathways of different medical centers. Cuneo, A.O. Santa Croce e Carle 380 To obtain information on the adherence to Clinical characteristics on 5869 patients the current guidelines. Trieste, Az. Osp.-Univ. Ospedali Riuniti 358 Bentivoglio (BO), Osp. di Bentivoglio 278 Inclusion Criteria Patients of any age that are admitted to the Giugliano In Campania (NA), 272 participating centers with a diagnosis of ACS Osp. Generale di Zona within 48 hours from the last symptomatic episode will be included in the study. We iden- Pedara (CT), Centro Cuore Morgagni 230 tify as necessary criteria for the diagnosis of Chiari (BS), Ospedale Civile Mellini 223 acute myocardial ischaemia a tipical clinical presentation associated with at least one of Pietra Ligure (SV), Osp. Santa Corona 215 the following: • Acute ischaemic modifications at the ECG - ST depression > or = 0.5 mm, transient ST elevation lasting <20 min, negative T waves >1 mm in at least two contiguous leads. - ST elevation, persistent at least 20 min, > or = 1 mm in two contiguous peripheral leads or >2 mm in two contiguous pre- cordial leads. • Biochemical evidence of myocardial necro- sis (CK, CK-MB, troponins). • Previous myocardial revascularization (PTCA or CABG) or documentation of CAD (coronary artery disease) with at least 50% stenosis of one of the major coronary ves- sels. • Documentation of previous myocardial infarction. Patients who present ACS during elective revascularization procedures (PTCA or CABG) will also be enrolled. Exclusion Criteria • Patients who present ACS secondary to confounding comorbidities (such as car accidents, traumas or non cardiac surgery) • No informed consent
  13. 13. SWEET-ACS Intensified Multifactorial Intervention on Hyperglycemic Patients with Acute Coronary Syndromes Steering Committee: G. Casella (Chairman), S. Del Prato, G. Di Pasquale, C. Fresco, M. Galvani, C. Greco, C. Giorda, A.P. Maggioni, G. Steffenino STUDY PARTIALLY SUPPORTED BY PFIZER BACKGROUND SAMPLE SIZE Despite the recent improvements of treatment of Acute Coronary Since the trial is event driven the number of events which are needed to Syndromes (ACS), hyperglycemia is still a marker of worse outcomes. demonstrate the superiority of the intensive strategy is set at 347, for a This finding has been extensively demonstrated for patients either with study power of 90% at the significance level =0,05. ST-elevated myocardial infarction (STE-MI) or with non ST-elevated To reach this number of events we plan to enroll 1.500 patients over a myocardial infarction (NSTE-MI), whether diabetes has been previously period of 18 months. diagnosed or not. Moreover, hyperglycemic patients without a previous history of diabetes have a higher mortality than diabetics when admitted for ACS. In addi- tion, blood glucose level represents a continuous variable with respect to cardiovascular risk and even milder elevations portend a poor prognosis. During the last few years, several studies demonstrated that an intensive insulin treatment improves outcomes of hyperglycemic, critical patients, with or without previous history of diabetes. However, it is not clear whether these effects are the consequence of better glycemic control or result from a direct favorable actions of insulin. Moreover, diabetes and hyperglycemia represent the hallmark of a more complex metabolic con- dition. In fact, tight control of blood pressure, dyslipidemia and glucose in type 2 diabetic patients is associated with evident benefits, both in primary and secondary prevention. Thus, it is legitimate to expect that these beneficial effects may be translated in ACS patients with milder impairment of glu- cose homeostasis. In spite of all these evidences, ACS patients with impaired glucose tolerance and diabetes are still undertreated. AIM OF THE STUDY To evaluate the application of current evidence-based strategies (and therapies) in patients with blood glucose levels ≥200 mg/dl with ACS and to assess the efficacy of an intensified, targeted, multifactorial intervention strategy targeted to several modifiable risk factors in patients with ACS and abnormal glucose tolerance (blood glucose ≥140 mg/dl and <200 mg/dl) on admission. STUDY POPULATION Patients of any age, admitted to the Italian CCU network with ACS with or without ST elevation and troponin positive, <24 hours from symptom onset and blood glucose on admission ≥140 mg/dl. STUDY CHARACTERISTICS The study has two parts: 1. Observational (outcome study) 2. Multicenter, prospective, randomized, open-label study (active study) 1) Outcome Study Patients with blood glucose levels on admission ≥200 mg/dl are enrolled in a 2-year observational, outcome study since current guidelines already STUDY ADVANCEMENT (as of May 5, 2008) recommend intensive medical treatment in such cases. All patients enrolled in the registry should be treated according to standard practice Study enrollment started on June 2007 Recruiting centers: 19 at local institutions and followed up for 2 years. Participating centers: 89 Enrolled patients in the Registry: 41 2) Intensified, Multifactorial, Intervention Study Activated centers: 44 Randomized patients: 45 Patients with or without known type 2 diabetes and blood glucose on admission ≥140 mg/dl and <200 mg/dl will be randomized (1:1) < 24 hours from symptom onset to aggressive or conventional treatment TOP TEN strategies. The same intensified treatment of the index ACS will be imple- Registry Randomized mented in both arms of the study during the acute phase. Center Pts Pts 1) Intensified multifactorial intervention strategy arm. Strict normalization of blood glucose levels during the acute phase of ACS (target fasting Cuneo, A.O. S. Croce e Carle 5 8 blood glucose: 80-110 mg/dl) will be pursued according to diabetologic consultations. Pozzuoli, Osp. S.M. Grazie 2 10 After discharge, such patients should undergo intensive treatment of their cardiovascular disease and risk factors, aiming at therapeutic goals more Savigliano, Osp. Maggiore 6 6 stringent than that stated in the ADA 2005 guidelines. 2) Conventional Care Treatment Arm. Strict normalization of blood glu- Teramo, Osp. Civile G. Mazzini 3 4 cose levels is not requested (in-hospital target glucose levels <140 mg/dl). Patients are treated at discretion of the attending physician Bologna, Osp. Maggiore 7 0 according to evidence-based international guidelines. Before discharge a secondary prevention program aiming at several modifiable risk factors L’Aquila, P.O. S. Salvatore 2 4 with therapeutic goals similar to that stated by the JNC 7 guidelines is rec- ommended. Parma, A.O. Universitaria 4 1 PRIMARY END POINT Composite end point of cardiovascular mortality, non fatal infarction, non Rieti, P.O. San Camillo 2 2 fatal stroke or hospitalization for heart failure. SECONDARY END POINTS Giugliano in Campania, Osp. Gen.le 3 1 Several clinical and biochemical or metabolic end points have been planned either at 30-days or at 2 Piombino, Osp. Villamarina 1 2 years follow-up.
  14. 14. STUDIES ENDORSED BY ANMCO CandHeart Effects of CANDesartan cilexitil vs standard therapy on serum levels of brain natriuretic peptide in patients suffering from chronic HEart fAilure with depressed and preseRved sysTolic function Steering Committee: G. Sinagra (Chairman), G.Cacciatore, R. Latini, A.P. Maggioni, G. Misuraca STUDY SUPPORTED BY TAKEDA RATIONALE - both genders, apy for CHF (group 1) or to the prosecution of Despite the improvements in the management of - stable NYHA II-IV class CHF with any LVEF, treat- their ongoing standard therapy for CHF (group 2). chronic heart failure (CHF), the risk of death ed with standard therapy including ACE- In order to allow for a sufficient number of CHF remains high for a consistent proportion of inhibitors and/or beta-blockers; for patients with patients with preserved LV systolic function patients. There is a need to search for prognostic LVEF 40%, at least 1 cardiovascular hospitalisa- (defined as LVEF 40%) to be enrolled, approxi- markers able to predict outcome. The B-type brain tion during the past 12 months is required, mately one third of the patients at each site should - written informed consent. belong to this group. natriuretic peptide (BNP), the only hormone syn- thesized in the heart and released in response to Drugs. Oral candesartan cilexetil (4 mg once daily up-titrated to the maximum dosage of 32 mg/die, STUDY ADVANCEMENT (as of May 5, 2008) increased ventricular wall stress, has been found to be a highly sensitive and specific marker for car- if tolerated) added to ongoing standard therapy Participating Centers: 105 diac dysfunction. Its circulating levels in patients for CHF, versus oral standard therapy (at dosages normally employed for CHF). Study enrollment started December 13, 2005 with CHF have been shown to be related to the Activated centers: 85 severity of the disease and mortality. Angiotensin Duration. 48-week treatment period. II type-1 receptor blockers (ARBs) significantly Objectives. The primary objective of the study is Randomizing centers: 70 reduce BNP plasma levels; however, there are no to assess, after a 3-month treatment period, the Enrolled patients: 498 formal evidences that a sustained reduction of cir- effects of candesartan, in addition to ongoing stan- culating levels of BNP may result in a significant dard CHF therapy versus standard CHF therapy, on Baseline characteristics clinical benefit and, moreover, there are no avail- circulating levels of BNP. Secondary objectives of the study are to assess, Males 371 (76%) able data on CHF patients with preserved LV sys- tolic function. after a 48-week treatment period: - circulating levels of BNP (48 weeks), Age (mean±SD) yrs 66.5±11.3 (range 30-94) STUDY DESIGN - circulating levels of aldosterone, pentraxin-3 (a >70 yrs 214 (44%) protein considered as an early indicator of Phase III, multi-centre, open-label, randomised trial myocyte irreversible injury in patients with designed to investigate the effects of candesartan, ischaemic cardiomyopathy), and C-reactive pro- NYHA II 352 (72%) as compared to standard therapy, in a large CHF tein (a marker of inflammation and a prognostic NYHA III 128 (26%) population, including patients with either pre- factor in patients with ischaemic cardiomyopa- served or reduced LV systolic function. NYHA IV 7 (1%) thy), Population. 1500 patients will be recruited in - NYHA functional class and quality of life, approximately 130 Italian Centres (100 Cardiology - LV dimensions, systolic and diastolic function. CHD etiology 245 (50%) sites and 30 Internal Medicine sites) in order to Design. Patients satisfying all the inclusion criteria have 650 assessable patients for each group. and none of the exclusion criteria will be enrolled EF% (mean±SD) 36±9.3 (range 10-75) The eligibility criteria are: in the study, being centrally randomised either to >40% 86 (18%) - age 18 years, candesartan added to their ongoing standard ther- ALOFT A twelve-week, randomized, double-blind, multi-center, placebo controlled, parallel group study to evaluate the safety and efficacy of aliskiren 150 mg when added to standard therapy in patients with stable heart failure Steering Committee: B. Pitt, J.J.V. McMurray, R. Latini, A.P. Maggioni STUDY SUPPORTED BY NOVARTIS OBJECTIVES 105 patients have been randomized by 25 centers. reducing plasma NT-pro BNP, plasma BNP and uri- The primary objective of this study is to evaluate Final results were presented at the ESC Congress nary aldosterone. the overall safety and tolerability of aliskiren when held in Wien in September 2007. The potential therapeutic role of aliskiren as alter- given in addition to standard therapy in hyperten- native or “add-on” therapy to an ACE inhibitor (or sive patients with stable heart failure. The study is S U M M A RY A N D C O N C L U S I O N S ARB) in HF is worth investigating further. further designed as an evaluation of the safety and Aliskiren effectively inhibited plasma renin activity, efficacy (neurohormonal biomarkers, cardiac even though most patients were treated with a hemodynamics, symptomatic relief of heart failure, beta-blocker. heart rate variability and quality of life assessment) Adding the direct renin inhibitor, aliskiren, in of aliskiren. This study will provide a preliminary patients also treated with an ACE inhibitor (or ARB) evaluation of the safety and efficacy of aliskiren in and, in a third of cases an aldosterone antagonist, order to support decisions about whether to con- appeared to be well tolerated. duct further outcome studies in this population. Aliskiren had favourable neurohumoral actions, STUDY DESIGN This is a 12 week, randomized, double-blind, multi-center, placebo controlled, parallel group study to evaluate the safety and efficacy of aliskiren (150 mg OD) versus placebo when added to stan- dard therapy in hypertensive patients with stable heart failure. STUDY POPULATION Men and women with essential hypertension and stable heart failure, and a baseline BNP >150 pg/mL. Overall 302 patients have been included. In Italy,