Wetenschappelijke publicaties

Transcriptie

1 Overzicht wetenschappelijke publicaties 2012

2 2013 Amphia Ziekenhuis Alle rechten voorbehouden. Niets uit deze uitgave mag worden verveelvoudigd, opgeslagen in een geautomatiseerd gegevensbestand, of openbaar gemaakt, in enige vorm of op enige wijze, hetzij elektronisch, mechanisch, door fotokopieën, opnamen, of enige andere manier, zonder voorafgaande toestemming van de uitgever. Voor zover het maken van kopieën uit deze uitgave is toegestaan op grond van artikel 16B Auteurswet 1912 j het Besluit van 20 juni 1974, St.b. 351, zoals gewijzigd bij Besluit van 23 augustus 1985, St.b. 471 en artikel 17 Auteurswet 1912, dient men de daarvoor wettelijk verschuldigde vergoedingen te voldoen aan de Stichting Reprorecht. Voor het overnemen van gedeelte(n) uit deze uitgave in bloemlezingen, readers en andere compilatie- of andere werken (artikel 16 Auteurswet 1912), in welke vorm dan ook, dient men zich tot de samenstellers/vormgever te wenden. De inzichten in de geneeskunde en wetenschap zijn voortdurend aan verandering onderhevig als gevolg van onderzoek en ervaring. De auteurs en uitgever zijn uiterst zorgvuldig te werk gegaan, om ervoor te zorgen dat de in dit boek verstrekte informatie, in overeenstemming is met de huidige kennis van zaken. Dit ontslaat de gebruiker van het boek echter niet van de verplichting om aan de hand van bestaande richtlijnen, protocollen en wetenschappelijke informatie te controleren of de daar verstrekte informatie afwijkt van de gegevens in dit boek en daarmee vast te stellen of de inhoud nog in overeenstemming is met de huidige stand van zaken ten aanzien van kennis en handelen. Ondanks alle aan de samenstelling van deze uitgave bestede zorg, zullen noch de samenstellers, noch de vormgever aansprakelijkheid aanvaarden voor eventuele schade die zou kunnen voortvloeien uit enige fout die in deze uitgave zou kunnen voorkomen. 2

3 Voorwoord Dit is het vijfde wetenschapsboek van het Amphia Ziekenhuis. Net als voorgaande jaren geeft het een goed overzicht van de diverse wetenschappelijke activiteiten van het afgelopen jaar. Veel specialisten hebben ook nu weer naast hun reguliere werkzaamheden bijgedragen aan wetenschappelijk onderzoek. Dit is noodzakelijk om de geneeskunde verder te brengen en genezing dichterbij. Hierin spelen STZ ziekenhuizen inmiddels een centrale rol. Door hun goede infrastructuur voor wetenschap en opleiding, en hun grote patiëntenpopulatie zijn zij de leveranciers van omvangrijke patiëntencohorten die noodzakelijk zijn voor de noodzakelijke bewijskracht (power) achter wetenschappelijke studies en experimenten. Gelukkig zijn steeds meer patiënten bereid om ook daaraan mee te werken. Op deze plaats is ook een woord van dank op zijn plaats aan al die patiënten die belangeloos meewerken aan nieuwe studies. Op het gebied van de primaire STZ-taken, te weten wetenschap, onderwijs en opleiding heeft het Amphia Ziekenhuis zich wederom bewezen. Door middel van de hier gepresenteerde onderzoeksresultaten, maar ook door een zeer geslaagde hernieuwing van haar lidmaatschap en het doorstaan van bijbehorende visitaties. Ik wens u veel genoegen met het doorlezen en spreek namens het Directiecomité mijn dank uit aan auteurs van de artikelen en de samenstellers van dit boek. Dr. J.J. (Hans) Meij, directeur Innovatie 3

4 Wetenschapsbureau In de zorg betaalt men voor de Mercedes evenveel als voor de Fiat Panda Decaan prof. dr. Jo Caris en wetenschapscoördinator dr. Attie Tuinenburg van het Wetenschapsbureau van de Amphia Academie zetten zich in voor meer wetenschappelijk onderzoek van hoog niveau. Dat gebeurt onder meer door het ondersteunen en stimuleren van onderzoekers. Een belangrijk uitgangspunt is integratie van zorg, opleiding en onderzoek, zowel voor de praktijk als in het beleid. Hiermee streven we naar een optimaal onderzoeksklimaat. Het Amphia Ziekenhuis is een Samenwerkend Topklinisch opleidingsziekenhuis (STZ). Anders dan bij academische ziekenhuizen valt het niet altijd mee om tijd vrij te maken voor onderzoek. Medici en paramedici besteden het grootste deel van hun tijd en aandacht aan de zorg voor patiënten, en terecht. Wetenschapscoördinator dr. Attie Tuinenburg (links) en decaan prof.dr. Jo Caris. Wetenschapsbureau 4

5 Attie Tuinenburg: Wat wij als wetenschapsbureau kunnen doen, is het voor de onderzoekers zo gemakkelijk mogelijk maken om onderzoek te doen. We kunnen ondersteunen met bijvoorbeeld methodologische en statistische hulp. Daarnaast verbeteren we de procedures rondom onderzoek binnen het ziekenhuis. Een belangrijk uitgangspunt voor het onderzoek in het Amphia Ziekenhuis is integratie van zorg, opleiding en onderzoek, zowel voor de praktijk als in het beleid. De nadruk ligt op de samenhang tussen de kwaliteit van zorg, de organisatie van zorg, en de kosten. We stimuleren onderzoek dat de eigen discipline overstijgt, dus waarbij zorgkernen samenwerken. Maatschappelijke relevantie Naast een duidelijk omschreven klinische relevantie benadrukken Caris en Tuinenburg ook het toenemende belang van de maatschappelijke relevantie van wetenschappelijk onderzoek. Zo kan een andere behandeling naast reductie van bijvoorbeeld morbiditeit ook leiden tot een snellere terugkeer van de patiënt op de arbeidsmarkt, of kan een minder invasieve behandeling leiden tot een hogere kwaliteit van leven en lagere kosten. De maatschappij (publiek, patiëntenorganisaties, politiek, verzekeraars) verwacht hiervoor tegenwoordig steeds meer aandacht. Bijna al het wetenschappelijk onderzoek dat in het Amphia Ziekenhuis wordt uitgevoerd bevat deze elementen zonder dat ze nadrukkelijk benoemd worden. Het accentueren van de klinische en maatschappelijke relevantie kan als voordeel hebben dat er eerder tweede en derde geldstromen beschikbaar worden gesteld ter financiering van het betreffende onderzoek. Organisatorisch onderzoek Het woord organisatie valt regelmatig tijdens het gesprek. Jo Caris is opgeleid als organisatiepsycholoog en zat dertig jaar lang in besturen van zorginstellingen. Hij promoveerde op het onderwerp Kwaliteit van consulten. Caris als hoogleraar Organisatieontwikkeling in de Zorg verbonden aan de TiasNimbas Business School (Universiteit Tilburg). Onderzoek via de Theory of Constraints (waarbij naar optimalisering van processen wordt gekeken) en de discussie over tussenafdelingen, zoals een PACU (post anesthesia care unit) zijn voorbeelden van organisatorische thema s met zorginhoudelijke en kwaliteitsconsequenties. Caris stelt dat de toenemende complexiteit van de zorg aanzet tot nadenken over beheersbaarheid en bestuurbaarheid. De zorg is de enige sector waar kwaliteit nog losgekoppeld is van kosten. Maar je koopt toch ook geen auto zonder dat daar een prijskaartje aan hangt? In de zorg betaalt men voor de Mercedes evenveel als voor de Fiat Panda. Maar als je een boodschappenwagen zoekt dan koop je toch geen Jaguar, als je de kosten zelf moet betalen? Voegt het waarde toe om personen van 93 jaar te opereren? Misschien wel, maar het is belangrijk om op voorhand wél die vraag te stellen en de consequenties goed te onderkennen. Wetenschapsbureau 5

6 Industrie-geïnitieerd en eigen onderzoek Waarom is het belangrijk dat er onderzoek in het Amphia Ziekenhuis plaatsvindt? Het is voor de kwaliteit van zorg van belang dat de zorgverleners op de hoogte zijn van de meest recente ontwikkelingen en onderzoeksresultaten. Door deel te nemen aan bijvoorbeeld industrie-geïnitieerd onderzoek staan de zorgverlener en de patiënt op de voorste rij wat betreft behandeling, antwoordt Tuinenburg. Maar ook studies geïnitieerd door onderzoekers uit het Amphia Ziekenhuis leiden tot verbetering van zorg of zorgprocessen waar de patiënt voordeel bij heeft. Tuinenburg benadrukt dat samenwerking met academische ziekenhuizen gestimuleerd wordt. Veel onderzoek wordt daar opgestart. Kennis, ervaring en data uit STZ-ziekenhuizen zijn daarbij onmisbaar. Attie Tuinenburg is opgeleid als arts en epidemioloog en deed haar promotieonderzoek (zowel lab- als klinisch onderzoek) naar hart- en vaatziekten en slagaderverkalking bij patiënten met stollingsstoornissen. In maart 2013 promoveerde ze. Deze functie past prima bij mij. Ik ben bezig met wetenschapsinhoud, methodologie en statistiek. Daarbij is een artsenopleiding een groot voordeel, ik kan snel schakelen en aansluiten bij de beroepspraktijk. Caris en Tuinenburg vullen elkaar naar eigen zeggen aan door de combinatie van methodisch en organisatorisch denken en dat zorgt voor een stevige bundeling van krachten. Ambitie en groei De wetenschap ontwikkelt zich in Amphia! Jo Caris en Attie Tuinenburg zijn recent gestart in het Amphia Ziekenhuis. Met Jan van Trier (bibliothecaris), Elmar Beekman (Kernproject Subsidies, Sponsoring en Fondsenwerving) en Birgitte Schaerlaeckens- Jordan (ambtelijk secretaris AMOA (Adviescommisssie Mensgebonden Onderzoek Amphia) vormen zij op dit moment het Wetenschapsbureau. Caris: De afgelopen weken hebben we veel onderzoekers gesproken. En de komende tijd richten we ons op wetenschappelijke inhoudelijke ondersteuning, beleidsontwikkeling, procesverbetering (AMOA/METC) en wetenschapspromotie. De komende jaren streven we naar een optimaal wetenschapsklimaat in het Amphia Ziekenhuis, waarbij het Wetenschapsbureau goed toegankelijk is en onderzoekers op alle benodigde gebieden kan ondersteunen. Wetenschapsbureau 6

7 Inhoud Anesthesiologie 8 Cardiologie 14 Cardiothoracale Chirurgie 35 Chirurgie 37 Dermatologie 64 Gynaecologie 65 Interne Geneeskunde en Maag- Darm- Levergeneeskunde 77 Keel-, Neus- en Oorheelkunde 86 Kindergeneeskunde 89 Klinisch Chemisch Hematologisch Laboratorium 95 Klinische Farmacie 99 Klinische Geriatrie 102 Laboratorium voor Microbiologie en Infectiepreventie 103 Longgeneeskunde 122 Mondziekten, Kaak- en Aangezichtschirurgie 136 Neurologie 139 Nucleaire Geneeskunde 142 Oogheelkunde 144 Orthopedie 147 Pathologie 158 Radiologie 159 Reumatologie 165 Seksuologie 170 Sportgeneeskunde 171 Urologie 172 Kwaliteit & Veiligheid 177 Zorginnovatie 182 Publicaties medisch specialisten Publicaties arts-assistenten Publicaties overige werknemers

8 Anesthesiologie Kerngegevens Zorgkern Anesthesiologie 28 anesthesiologen: A. (Anna) Besselink-Lobanova, S.F. (Sjoerd) de Boer, H.P. (Henk) van Driel, M.J.P.G. (Maarten) van Eerd, F.E.A. (Ferd) Geisler, G. (Gerhard) van Gelder, dr. B.M. (Bas) Gerritse, C. (Carla) van Gompel, dr. V.L.H. (Vincent) Hoffmann, L.H. (Lode) Jacobs, G.M.J. (Greg) Jansen, A. (Aad) van Keeken, J.D.L. (Johan) Konings, E.B. (Edmund) Lachitjaran, F. (Frank) de Loos, P.P.M. (Paul) Maas, dr. B.J.M. (Nardo) van der Meer, R.J. (Robert) Meulemans, F.X. (Frank) O Connor, P.M.J. (Peter) Rosseel, T.A. (Tom) Rijpstra, D.B. (David) Schockman, T.V. (Thierry) Scohy, G.C.H. (Gilbert) Tjiang, W.A. (Anton) Visser, M.A.J. (Michael) Voets, E. (Erik) Winters, S.I.M. (Simone) van Zijll Langhout-Kokke. 5 assistenten niet in opleiding 3 assistenten in opleiding Chef de clinique: P.A.V. (Peter) Frietman, P. (Pim) van der Heiden, I. (Iris) Witsch Internist-intensivist: R.A.L. (Ruud) de Waal, F.J. (Frits) Schuitemaker Longarts-intensivist: H.N.A. (Huub) Belderbos Samenvattingen gepubliceerde artikelen Van der Kleij SC, Koolen BB, Newhall DA, Gerritse BM, Rosseel PM, Rijpstra TA, Geisler FE, van der Meer NJ.Clinical evaluation of a new tracheal impedance cardiography method. Anaesthesia Jul;67(7): Epub 2012 Mar 15. Non-invasive cardiac output measurement by means of impedance cardiography has been evaluated before, and agreement with other methods has been variable. We decided to study a newly developed tracheal impedance device, that is claimed to be more accurate and reliable. This incorporates new software and mathematical formulae, that are designed to reduce signal noise from diathermy, leading to improved accuracy. In 25 cardiothoracic surgery patients, simultaneous measurements were performed using both pulmonary artery thermodilution and the tracheal impedance device, at five peri-operative time points: before skin incision; after weaning from cardiopulmonary bypass; after sternal closure; and 30 min and 2 h after arrival in the intensive care unit. Mean cardiac output, bias and 95% limits of agreement were 5.3, 0.03 and -2.8 to 2.8 l.min(-1), respectively. Tracheal impedance showed good correla tion with measurement trends using thermodilution in 88% of measurements, with a mean (95% limit of agreement) angular bias of -9.0 (-83.3 to 65.3 ). However, the wide limits of agreement and high percentage error of 53% that were apparent in this study mean that, in its present guise, tracheal impedance is not an acceptable alternative to thermodilution in cardiac surgical patients. Anaesthesia 2012 The Association of Anaesthetists of Great Britain and Ireland. PMID: Anesthesiologie 8

9 Dieleman JM, Nierich AP, Rosseel PM, van der Maaten JM, Hofland J, Diephuis JC, Schepp RM, Boer C, Moons KG, van Herwerden LA, Tijssen JG, Numan SC, Kalkman CJ, van Dijk D; Dexamethasone for Cardiac Surgery (DECS) Study Group*. [van der Meer NJ et al...]. Intraoperative high-dose dexamethasone for cardiac surgery: a randomized controlled trial. JAMA Nov 7;308(17): CONTEXT: Prophylactic corticosteroids are often administered during cardiac surgery to attenuate the inflammatory response to cardiopulmonary bypass and surgical trauma; however, evidence that routine corticosteroid use can prevent major adverse events is lacking. OBJECTIVE: To quantify the effect of intraoperative high-dose dexamethasone on the incidence of major adverse events in patients undergoing cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, double-blind, placebo-controlled trial of 4494 patients aged 18 years or older undergoing cardiac surgery with cardiopulmonary bypass at 8 cardiac surgical centers in The Netherlands enrolled between April 13, 2006, and November 23, INTERVENTION: Patients were randomly assigned to receive a single intraoperative dose of 1 mg/kg dexamethasone (n = 2239) or placebo (n = 2255). MAIN OUTCOME MEASURES: A composite of death, myocardial infarction, stroke, renal failure, or respiratory failure, within 30 days of randomization. RESULTS: Of the 4494 patients who underwent randomization, 4482 (99.7%) could be evaluated for the primary outcome. A total of 157 patients (7.0%) in the dexamethasone group and 191 patients (8.5%) in the placebo group reached the primary study end point (relative risk, 0.83; 95% CI, ; absolute risk reduction, -1.5%; 95% CI, -3.0% to 0.1%; P =.07). Dexamethasone was associated with reductions in postoperative infection, duration of postoperative mechanical ventilation, and lengths of intensive care unit and hospital stays. In contrast, dexamethasone was associated with higher postoperative glucose levels. CONCLUSION: In our trial of adults undergoing cardiac surgery, the use of intraoperative dexamethasone did not reduce the 30-day incidence of major adverse events compared with placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT Anesthesiologie 9

10 Collaborators (42) : Bredée JJ, Buhre WF, Dieleman JM, van Dijk D, van Herwerden LA, Kalkman CJ, van Klarenbosch J, Moons KG, Nathoe HM, Numan SC, Ottens TH, Roes KC, Sauer AM, Slooter AJ, Nierich AP, Ennema JJ, Rosseel PM, van der Meer NJ, van der Maaten JM, Cernak V, Hofland J, van Thiel RJ, Diephuis JC, Schepp RM, Haenen J, de Lange F, Boer C, de Jong JR, Tijssen JG, Hofland J, de Jong JR. PMID: Van Seventer R, Vos C, Giezeman M, Meerding WJ, Arnould B, Regnault A, van Eerd M, Martin C, Huygen F. Validation of the Dutch Version of the DN4 Diagnostic Questionnaire for Neuropathic Pain. Pain Pract Jun;13(5): Epub 2012 Oct 31. Difficulties in diagnosing neuropathic pain in routine clinical practice support the need for validated and easy-to-use diagnostic tools. The DN4 neuropathic pain diagnostic questionnaire aims to discriminate neuropathic pain from nociceptive pain, but needs clinical validation. A total of 269 patients with chronic pain in three pain clinics were included in the study of which 248 had analyzable data. The mean duration of pain was 4.9 years. The most frequent etiologies were posttraumatic (36%), (pseudo) radicular (14%), and mechanical back pain (12%). The mean intensity of pain at visit was 5.6 on a 0-10 scale. Hundred and ninety-six of 248 patients had an identical pain diagnosis from both physicians: 85 had neuropathic pain, 57 had nociceptive pain, and 54 had mixed pain. Among patients with identical diagnoses of neuropathic or nociceptive pain, using a receiver operating characteristic curve analysis, the area under the curve (AUC) was 0.81 for the DN4 7-item and 0.82 for the 10-item version. A cutoff point of 5/10 for the full questionnaire resulted in a sensitivity of 75% and a specificity of 79%, while a cutoff point of 4/7 for the partial questionnaire resulted in a sensitivity of 74% and a specificity of 79%. The items brushing, painful cold, and numbness were most discriminating. The DN4 is an easy-to-use screening tool that is reliable for discriminating between neuropathic and nociceptive pain conditions in daily practice. Item-specific scores provide important information in addition to the total score The Authors Pain Practice 2012 World Institute of Pain. PMID: Hulsman N, Gerritse BM. Het cardiale trauma. A&I : nascholingstijdschrift over perioperatieve geneeskunde. 2012;4(4): Cardiaal letsel kan worden onderverdeeld in stomp en penetrerend letsel. Stompe cardiale traumata kunnen, afhankelijk van de omvang van het trauma, worden onderverdeeld in een contusio en een commotio cordis. Ook kan bij een hoogener- Anesthesiologie 10

11 getisch trauma letsel ontstaan aan de anatomische structuren van het hart (hartkleppen, coronairarteriën en septum). De belangrijkste complicatie van stomp en penetrerend cardiaal letsel is een tamponnade. Bij de opvang van een multitrauma is het herkennen van cardiaal letsel en eventuele complicaties cruciaal. Niemeijer ND, van Daele PL, Caliskan K, Oei FB, Loosveld OJ, van der Meer NJ. Löffler endocarditis: a rare cause of acute cardiac failure. J Cardiothorac Surg Oct 10;7(1):109. [Epub ahead of print] We describe a patient with acute cardiogenic shock due to cardiac involvement in idiopathic hypereosinophilic syndrome (Loffler endocarditis). At the echocardiography, there was a huge mass in the left ventricular cavity, resulting in inflow- and outflow tract obstruction. The posterior leaflet of the mitral valve apparatus was completely embedded in a big (organized) thrombus mass. The patient was treated with high dose corticosteroids, however without effect. Partial remission was achieved after treatment with hydroxycarbamide. He was also treated with anticoagulants and high dose beta-blockers. The patient s condition improved remarkably after correction of the mitral valve insufficiency by a mitral valve bioprothesis. PMID: Jansen NE, van Leiden HA, Haase-Kromwijk BJ, van der Meer NJ, Vorstius Kruijff EV, van der Lely N, van Zon H, Meinders AJ, Mosselman MJ, Hoitsma AJ. Inzet van getrainde donatiedeskundigen: vaker toestemming van nabestaanden voor orgaanen weefseldonatie* [Appointing trained donation practitioners results in a higher family consent rate in the Netherlands: a multicenter study]. Ned Tijdschr Geneeskd. 2012;156(6):A4300. [ ]. OBJECTIVE: The process of obtaining consent for organ and tissue donation is complex for both families and professionals. The objective of this study was to assess whether the long-term guidance of the relatives of ICU patients, in combination with the training of staff on communicating on organ donation, is of overriding importance in increasing the donation consent rate. A multicentre study was conducted at 3 hospitals for this purpose. DESIGN: Multicentre study. METHOD: We compared the family consent rate for donation at 1 intervention hospital with those from 2 control hospitals between December 2007 and November At the intervention hospital, trained donation practitioners guided 66 families throughout the ICU hospitalisation until they had reached decisions regarding donation. At the first control hospital, where no family guidance or training took place, 107 families were approached. At the second control hospital, hostesses not trained in discussing Anesthesiologie 11

12 donation-related questions supported 99 families during the period of hospitalisation. A total of 272 families of potential donors were approached and asked to consent for donation. We compared consent rates, and evaluated the families experiences by means of a questionnaire sent approximately 4 months after death. RESULTS: Family consent rates were significantly higher at the intervention hospital (57.6%) than at the control hospitals (34.6% and 39.4%, respectively). The response rate to the questionnaire was 69%. The answers revealed no confounding variables that could have influenced the consent rate. CONCLUSION: The appointment of trained donation practitioners at the intervention hospital, who guided families during the period of ICU hospitalisation and the dona tion decision-making process, resulted in a significantly higher consent rate. Comment in [More donation: through the community, the government or the market?]. [Ned Tijdschr Geneeskd. 2012] [More donation: through the community, the government or the market?]. Bos GM. Ned Tijdschr Geneeskd. 2012; 156(6):A4556. PMID: Scohy Th V. Perioperatieve driedimensionale transoesofagiale echocardiografie : Inleiding in de praktische toepassing. A&I dec;4(4). 3D TEE is een logisch vervolg op de 2D-echocardiografie en stelt ons in staat om perioperatief betrouwbare en gedetailleerde uitspraken te doen, m.n. aangaande klepafwijkingen. De 3D echografische technologie moet gezien worden als een aanvulling op de al bestaande 2D en dopplerechografie. 3D-echocardiografie heeft een duidelijk voordeel wat betreft LVEF-meting en morfologische en functionele analyse van hartafwijkingen. Toekomstig onderzoek zal deze nieuwe technologie in het juiste perspectief plaatsen. Visser WA, Ermens AA, De Boer HD, Van Os E. Rocuronium reversed by sugammadex for electroconvulsive therapy in a patient with prolonged duration of action of succinylcholine. Anaesth Intensive Care Nov;39(6): No abstract available. Comment on: Anaesth Intensive Care Jul;39(4): PMID: Anesthesiologie 12

13 Visser WA. Spinal anesthesia failure after local anesthetic injection into cerebrospinal fluid. Reg Anesth Pain Med Nov-Dec;36(6):631. Comment on: Reg Anesth Pain Med Jul-Aug;36(4): Fuzier R [et al...]: Spinal anesthesia failure after local anesthetic injection into cerebrospinal fluid: a multicenter prospective analysis of its incidence and related risk factors in 1214 patients. PMID: Xxx 13

14 Cardiologie Kerngegevens Zorgkern Cardiologie 15 cardiologen: dr. A.M.W. (Marco) Alings, dr. B.J.L. (Ben) van den Branden, W.A.J. (Wim) Bruggeling, dr. P.H.J.M. (Peter) Dunselman, H.P.J. (Henry) de Haan, dr. P. (Peter) den Heijer, dr. B. (Bart) Hooft van Huysduynen, dr. M. (Martijn) Meuwissen, S.G (Sander) Molhoek, dr. J. (Jeroen) Schaap, dr. B. (Bas) Schölzel, dr. S. (Sipke) Strikwerda, dr. J. (Jeroen) Vos, dr. R.P. (Rob) Wielenga, dr. W.J.M. Dewilde chef de clinique: dr. D.P.W. (Driek) Beelen, cardioloog 3 assistenten in opleiding 10 assistenten niet in opleiding 4 verpleegkundig specialisten Subspecialismen: algemene cardiologie (hart- en vaatziekten in brede zin), beeldvorming (echocardiografie, cardiale CT en MRI), interventiecardiologie (stenten dotterbehandelingen, vervanging hartklep), elektrofysiologie (behandeling van hartritmestoornissen) Samenvattingen gepubliceerde artikelen Van der Werf C, Nederend I, Hofman N, van Geloven N, Ebink C, Frohn-Mulder IM, Alings AM, Bosker HA, Bracke FA, van den Heuvel F, Waalewijn RA, Bikker H, van Tintelen JP, Bhuiyan ZA, van den Berg MP, Wilde AA. Familial evaluation in catecholaminergic polymorphic ventricular tachycardia: disease penetrance and expression in cardiac ryanodine receptor mutation-carrying relatives. Circ Arrhythm Electrophysiol Aug 1;5(4): Epub 2012 Jul 10. BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene (Ryr2) in the majority of patients. Previous studies of CPVT patients mainly involved probands, so current insight into disease penetrance, expression, genotype-phenotype correlations, and arrhythmic event rates in relatives carrying the Ryr2 mutation is limited. METHODS AND RESULTS: One-hundred sixteen relatives carrying the Ryr2 mutation from 15 families who were identified by cascade screening of the Ryr2 mutation causing CPVT in the proband were clinically characterized, including 61 relatives from 1 family. Fifty-four of 108 antiarrhythmic drug-free relatives (50%) had a CPVT phenotype at the first cardiological examination, including 27 (25%) with nonsustained ventricular tachycardia. Relatives carrying a Ryr2 mutation in the C-terminal channelforming domain showed an increased odds of nonsustained ventricular tachycardia (odds ratio, 4.1; 95% CI, ; P=0.007, compared with N-terminal domain) compared with N-terminal domain. Sinus bradycardia was observed in 19% of relatives, whereas other supraventricular dysrhythmias were present in 16%. Ninety-eight (most actively treated) relatives (84%) were followed up for a median of 4.7 years (range, years). During follow-up, 2 asymptomatic relatives experienced exercise-induced syncope. One relative was not being treated, whereas the other was noncompliant. Cardiologie 14

15 None of the 116 relatives died of CPVT during a 6.7-year follow-up (range, years). CONCLUSIONS: Relatives carrying an Ryr2 mutation show a marked phenotypic diversity. The vast majority do not have signs of supraventricular disease manifestations. Mutation location may be associated with severity of the phenotype. The arrhythmic event rate during follow-up was low. PMID: Van den Broek KC, Kupper N, van der Voort PH, Alings M, Denollet J, Nyklícek I. Trajectories of Perceived Emotional and Physical Distress in Patients with an Implantable Cardioverter Defibrillator. Int J Behav Med Nov 17. [Epub ahead of print]. BACKGROUND: Little is known about the course of emotional and physical distress in patients with an implantable cardioverter defibrillator (ICD). PURPOSE: We examined (1) trajectories of emotional and physical distress in the first 18 months postimplantation and (2) predictors of these trajectories, including demographical, clinical, and personality factors. METHODS: Dutch patients with an ICD (N?=?645) completed measures on anxiety, depression, somatic symptoms, and perceived disability at the time of implantation, and 2, 12, and 18 months postimplantation. Measures on Type D personality (tendency to inhibit the expression of negative emotions) and anxiety sensitivity (tendency to fear anxiety-related sensations) were also completed at baseline. RESULTS: Latent class analysis (LatentGOLD) identified six to seven distinct trajectories, varying largely in overall levels of distress, and remaining relatively stable after a small initial decline. Multinomial regression showed that Type D personality and anxiety sensitivity were the most prominent predictors, particularly of trajectories that reflected higher distress levels. Cardiac resynchronization therapy and coronary artery disease also increased the risk for distress, whereas ICD indication and shocks did not. CONCLUSIONS: The course of emotional and physical distress may be relatively stable after ICD implantation. In clinical practice, identification of patients with high risk of higher levels of emotional and physical distress may be warranted; as such, patients with high levels of anxiety sensitivity or a Type D personality should be identified and offered behavioral support. PMID: Cardiologie 15

16 Borer JS, Böhm M, Ford I, Komajda M, Tavazzi L, Sendon JL, Alings M, Lopez-de-Sa E, Swedberg K; SHIFT Investigators*. Effect of ivabradine on recurrent hospitalization for worsening heart failure in patients with chronic systolic heart failure: the SHIFT Study. Eur Heart J Nov;33(22): Epub 2012 Aug 27. AIMS: We explored the effect of treatment with ivabradine, a pure heart rate-slowing agent, on recurrent hospitalizations for worsening heart failure (HF) in the SHIFT trial. METHODS AND RESULTS: SHIFT was a double-blind clinical trial in which 6505 patients with moderate-to-severe HF and left ventricular systolic dysfunction, all of whom had been hospitalized for HF during the preceding year, were randomized to ivabradine or to placebo on a background of guideline-recommended HF therapy (including maximized ß-blockade). In total, 1186 patients experienced at least one additional HF hospitalization during the study, 472 suffered at least two, and 218 suffered at least 3. Patients with additional HF hospitalizations had more severe disease than those without. Ivabradine was associated with fewer total HF hospitalizations [902 vs events with placebo; incidence rate ratio, 0.75, 95% confidence interval (CI), , P = ] during the 22.9-month median follow-up. Ivabradine-treated patients evidenced lower risk for a second or third additional HF hospitalization [hazard ratio (HR): 0.66, 95% CI, , P < and HR: 0.71, 95% CI, , P = 0.012, respectively]. Similar observations were made for all-cause and cardiovascular hospitalizations. CONCLUSION: Treatment with ivabradine, on a background of guidelines-based HF therapy, is associated with a substantial reduction in the likelihood of recurrent hospitalizations for worsening HF. This benefit can be expected to improve the quality of life and to substantially reduce health-care costs. Comment in: Time to move on from time-to-first : should all events be included in the analysis of clinical trials? [Eur Heart J. 2012] Time to move on from time-to-first : should all events be included in the analysis of clinical trials?anker SD, McMurray JJ. Eur Heart J Nov; 33(22): Epub 2012 Aug 27. PMID: Easton JD, Lopes RD, Bahit MC, Wojdyla DM, Granger CB, Wallentin L, Alings M, Goto S, Lewis BS, Rosenqvist M, Hanna M, Mohan P, Alexander JH, Diener HC; ARISTOTLE Committees and Investigators Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial. Lancet Neurol Jun;11(6): Epub 2012 May 8. BACKGROUND: In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Pa Cardiologie 16

17 tients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. METHODS: Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18,201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio ). The median duration of follow-up was 1 8 years (IQR ). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC FINDINGS: Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2 46 per 100 patient-years of follow-up in the apixaban group and 3 24 in the warfarin group (hazard ratio [HR] 0 76, 95% CI 0 56 to 1 03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1 01 per 100 patient-years of follow-up with apixaban and 1 23 with warfarin (HR 0 82, 95% CI 0 65 to 1 03; p for interaction=0 71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0 77 per 100 patient-years of follow-up (95% CI to 1 63) in patients with and 0 22 (-0 03 to 0 47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1 07 per 100 patient-years (95% CI ) in patients with and 0 93 ( ) in those without previous stroke or TIA. INTERPRETATION: The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population. FUNDING: Bristol-Myers Squibb and Pfizer. Copyright 2012 Elsevier Ltd. All rights reserved. *Collaborators (1129) Erratum in: Lancet Neurol Dec;11(12):1021. Comment in: Reducing the risk of recurrent stroke in patients with AF.Hart RG, Eikelboom JW. Lancet Neurol Jun; 11(6): Epub 2012 May 8. PMID: Cardiologie 17

18 Bogale N, Priori S, Cleland JG, Brugada J, Linde C, Auricchio A, van Veldhuisen DJ, Limbourg T, Gitt A, Gras D, Stellbrink C, Gasparini M, Metra M, Derumeaux G, Gadler F, Buga L, Dickstein K; Scientific Committee, National Coordinators, and Investigators* [Alings M et al...]. The European CRT Survey: 1 year (9-15 months) follow-up results. Eur J Heart Fail Jan;14(1): METHODS AND RESULTS: Patients who had a successful CRT implantation were enrolled from 141 centres in 13 countries between November 2008 and June Baseline demographics, clinical and implantation data were collected, with a follow-up of ~1 year (9-15 months). The current report describes clinical outcomes including symptom severity, cardiovascular (CV) hospitalization, and survival. A total of 2438 patients were enrolled, and follow-up data were acquired from 2111 patients (87%). The population included important groups of patients poorly represented in randomized controlled trials, including very elderly patients and those with prior device implantation, atrial fibrillation, and/or QRS duration <120 ms. Investigators reported substantial improvement in New York Heart Association (NYHA) functional class at follow-up. Patient selfassessment indicated that 81% of the patients felt improved, 16% reported no change, and 4% reported deterioration. During follow-up, 207 (10%) patients died, 346 (16%) had a CV hospitalization, and 501 (24%) died or had CV hospitalization. Worse NYHA functional class, atrial fibrillation, ischaemic aetiology, and device type (CRT-P, i.e. CRT alone) were associated with poorer survival. Women had a better outcome, as did patients who had a CRT-D (with an implantable cardioverter defibrillator function) device. CONCLUSIONS: Outcomes including death and hospitalization in this European CRT survey were consistent with results from clinical trials of CRT. At 1 year follow-up, most patients who received a CRT device considered their symptoms improved compared with their pre-implant assessment. Although prospective, this is an observational study of successful CRT implantations, and outcomes in subgroup analyses must be interpreted with appropriate conservatism. *Collaborators (40): Dickstein K, Priori S, Auricchio A, Bogale N, Brugada J, Cleland JG, Derumeaux G, Gitt A, Gras D, Komajda M, Linde C, Morgan J, van Veldhuisen DJ, Fruhwald F, Strohmer B, Goethals M, Vijgen J, Trochu JN, Gras D, Kindermann M, Stellbrink C, McDonnald K, Keane D, Ben Gal T, Glikson M, Metra M, Gasparini M, Maass A, Jordaens L, Alings M, Larsen AI, Færestrand S, Delgado J, Mont L, Persson H, Gadler F, Brunner-La Rocca HP, Osswald S, Squire I, Morgan J. PMID: Cardiologie 18

19 Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, Chaitman BR, Holme IM, Kallend D, Leiter LA, Leitersdorf E, McMurray JJ, Mundl H, Nicholls SJ, Shah PK, Tardif JC, Wright RS; dal-outcomes Investigators* [Alings MA et al...]. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med Nov 29;367(22): Epub 2012 Nov 5. BACKGROUND: In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes. METHODS: We randomly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or placebo, in addition to the best available evidence-based care. The primary efficacy end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation. RESULTS: At the time of randomization, the mean HDL cholesterol level was 42 mg per deciliter (1.1 mmol per liter), and the mean low-density lipoprotein (LDL) cholesterol level was 76 mg per deciliter (2.0 mmol per liter). Over the course of the trial, HDL cholesterol levels increased from baseline by 4 to 11% in the placebo group and by 31 to 40% in the dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels. Patients were followed for a median of 31 months. At a prespecified interim analysis that included 1135 primary end-point events (71% of the projected total number), the independent data and safety monitoring board recommended termination of the trial for futility. As compared with placebo, dalcetrapib did not alter the risk of the primary end point (cumulative event rate, 8.0% and 8.3%, respectively; hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P=0.52) and did not have a significant effect on any component of the primary end point or total mortality. The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo (P<0.001 for both comparisons). CONCLUSIONS: In patients who had had a recent acute coronary syndrome, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events. (Funded by F. Hoffmann-La Roche; dal-outcomes ClinicalTrials. gov number, NCT ). Comment in Dalcetrapib in patients with an acute coronary syndrome. [N Engl J Med. 2013] Dalcetrapib in patients with an acute coronary syndrome.schwartz GG, Olsson AG, Barter PJ. N Engl J Med Feb 28; 368(9): Cardiologie 19

20 Dalcetrapib in patients with an acute coronary syndrome. [N Engl J Med. 2013] Dalcetrapib in patients with an acute coronary syndrome.tomoda H. N Engl J Med Feb 28; 368(9):869. Lipids. Dalcetrapib raises HDL-cholesterol level, but does not reduce cardiac risk. [Nat Rev Cardiol. 2013] Lipids. Dalcetrapib raises HDL-cholesterol level, but does not reduce cardiac risk.lim GB. Nat Rev Cardiol Jan; 10(1):5. Epub 2012 Nov 20. *Collaborators (1041) PMID: Teeuwen K, Adriaenssens T, Van den Branden BJ, Henriques JP, Van der Schaaf RJ, Koolen JJ, Vermeersch PH, Bosschaert MA, Tijssen JG, Suttorp MJ. A randomized multicenter comparison of hybrid sirolimus-eluting stents with bioresorbable polymer versus everolimus-eluting stents with durable polymer in total coronary occlusion: rationale and design of the Primary Stenting of Occluded Native Coronary Arteries IV study. Trials Dec 15;13:240. BACKGROUND: Percutaneous recanalization of total coronary occlusion (TCO) was historically hampered by high rates of restenosis and reocclusions. The PRISON II trial demonstrated a significant restenosis reduction in patients treated with sirolimuse luting stents compared with bare metal stents for TCO. Similar reductions in restenosis were observed with the second-generation zotarolimus-eluting stent and everolimuseluting stent. Despite favorable anti-restenotic efficacy, safety concerns evolved after identifying an increased rate of very late stent thrombosis (VLST) with drug-eluting stents (DES) for the treatment of TCO. Late malapposition caused by hyper sensitivity reactions and chronic inflammation was suggested as a probable cause of these VLST. New DES with bioresorbable polymer coatings were developed to address these safety concerns. No randomized trials have evaluated the efficacy and safety of the newgeneration DES with bioresorbable polymers in patients treated for TCO. METHODS/DESIGN: The prospective, randomized, single-blinded, multicenter, noninferiority PRISON IV trial was designed to evaluate the safety, efficacy, and angiographic outcome of hybrid sirolimus-eluting stents with bioresorbable polymers (Orsiro; Biotronik, Berlin, Germany) compared with everolimus-eluting stents with durable polymers (Xience Prime/Xpedition; Abbott Vascular, Santa Clara, CA, USA) in patients with successfully recanalized TCOs. In total, 330 patients have been randomly allocated to each treatment arm. Patients are eligible with estimated duration of TCO =4 weeks with evidence of ischemia in the supply area of the TCO. The primary endpoint is insegment late luminal loss at 9-month follow-up angiography. Secondary angiographic endpoints include in-stent late luminal loss, minimal luminal diameter, percentage of diameter stenosis, in-stent and in-segment binary restenosis and reocclusions at 9-month follow-up. Additionally, optical coherence tomography is performed in the Cardiologie 20

21 first 60 randomized patients at 9 months to assess neointima thickness, percentage of neointima coverage, and stent strut malapposition and coverage. Personnel blinded to the allocated treatment will review all angiographic and optical coherence assessments. Secondary clinical endpoints include major adverse cardiac events, clinically driven target vessel revascularization, target vessel failure and stent thrombosis to 5-year clinical follow-up. An independent clinical event committee blinded to the allocated treatment will review all clinical events. TRIAL REGISTRATION: Clinical Trials.gov: NCT Patient recruitment started in February PMID: PMCID: PMC Post S, Post MC, van den Branden BJ, Eefting FD, Goumans MJ, Stella PR, van Es HW, Wildbergh TX, Rensing BJ, Doevendans PA. Early statin treatment prior to primary PCI for acute myocardial infarction: REPERATOR, a randomized placebo-controlled pilot trial. Catheter Cardiovasc Interv Nov 1;80(5): Epub 2012 Mar 14. OBJECTIVE: The aim of this pilot study was to determine whether early atorvastatin treatment will reduce left ventricle (LV) remodeling, infarct size, and improve microvascular perfusion. BACKGROUND: In animal studies, early statin therapy reduces reperfusion injury after a percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). METHODS: Forty-two consecutive patients (82% male, mean age 61.2 ± 9.8) who underwent a primary PCI for a first ST-elevated AMI were randomized for pretreatment with atorvastatin 80 mg (n = 20) or placebo (n = 22) and continued with the same dosage daily for 1 week. All patients received atorvastatin 80 mg once daily 7 days after primary PCI. The LV function and infarct size were measured by magnetic resonance imaging within 1 day, at 1 week, and 3 months follow up. The primary endpoint was the end-systolic volume index (ESVI) at 3 months. Secondary endpoints were global LV function measurements, myocardial infarct size, biochemical cardiac markers, TIMI flow, and ST-T elevation resolution. RESULTS: ESVI 3 months after AMI was 25.1 ml/m(2) in the atorvastatin arm and 25.0 ml/m(2) in the placebo arm (P = 0.74). The differences in change from baseline to 3 months follow up in global LV function and myocardial infarct size did not differ between both treatment arms. Furthermore, biochemical markers, TIMI flow, and ST-T elevation resolution did not differ between atorvastatin and placebo arm. Cardiologie 21

22 CONCLUSIONS: In this pilot study, pretreatment with atorvastatin in an acute myocardial infarction does not result in an improved cardiac function, microvascular perfusion, or decreased myocardial infarct size. Copyright 2012 Wiley Periodicals, Inc. Cardiologie 22

23 Comment in: Statin pleiotropy in acute myocardial infarction--is it about timing? [Catheter Cardiovasc Interv. 2012] Statin pleiotropy in acute myocardial infarction--is it about timing?puri R, Tuzcu EM. Catheter Cardiovasc Interv Nov 1; 80(5): PMID: Van den Branden BJ, Swaans MJ, Post MC, Rensing BJ, Eefting FD, Jaarsma W, Van der Heyden JA. Percutaneous edge-to-edge mitral valve repair in high-surgical-risk patients: do we hit the target? JACC Cardiovasc Interv Jan;5(1): OBJECTIVES: This study sought to assess the feasibility and safety of percutaneous edgeto-edge mitral valve (MV) repair in patients with an unacceptably high operative risk. BACKGROUND: MV repair for mitral regurgitation (MR) can be accomplished by use of a clip that approximates the free edges of the mitral leaflets. METHODS: All patients were declined for surgery because of a high logistic EuroSCORE (>20%) or the presence of other specific surgical risk factors. Transthoracic echocardiography was performed before and 6 months after the procedure. Differences in New York Heart Association (NYHA) functional class, quality of life (QoL) using the Minnesota questionnaire, and 6-min walk test (6-MWT) distances were reported. RESULTS: Fifty-five procedures were performed in 52 patients (69.2% male, age 73.2 ± 10.1 years, logistic EuroSCORE 27.1 ± 17.0%). In 3 patients, partial clip detachment occurred; a second clip was placed successfully. One patient experienced cardiac tamponade. Two patients developed inguinal bleeding, of whom 1 needed surgery. Six patients (11.5%) died during 6-month follow-up (5 patients as a result of progressive heart failure and 1 noncardiac death). The MR grade before repair was =3 in 100%; after 6 months, a reduction in MR grade to =2 was present in 79% of the patients. Left ventricular (LV) end-diastolic diameter, LV ejection fraction, and systolic pulmonary artery pressure improved significantly. Accompanied improvements in NYHA functional class, QoL index, 6-MWT distances, and log N-terminal pro-b-type natriuretic peptide were observed. CONCLUSIONS: In a high-risk population, MR reduction can be achieved by percutaneous edge-to-edge valve repair, resulting in LV remodeling with improvement of functional capacity after 6 months. Copyright 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. PMID: Cardiologie 23

24 Van den Branden BJ, Rahel BM, Laarman GJ, Slagboom T, Kelder JC, Ten Berg JM, Suttorp MJ. Five-year clinical outcome after primary stenting of totally occluded native coronary arteries: a randomised comparison of bare metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions (PRISON II study). EuroIntervention Feb;7(10): AIMS: The aim of this study was to examine the five-year clinical outcome in patients enrolled in the Primary Stenting of Totally Occluded Native Coronary Arteries II (PRI SON II) study. METHODS AND RESULTS: Patients with totally occluded coronary arteries were randomised to either sirolimus-eluting stent (SES, n=100) or bare metal stent (BMS, n=100) implantation. At five years, patients in the SES group had significantly lower rates of target lesion revascularisation (12% vs. 30%, p=0.001), target vessel revascularisation (17% vs. 34%, p=0.009) and major adverse cardiac events (12% vs. 36%, p<0.001). There were no significant differences in death and myocardial infarction. Eight (8%) cases of stent thrombosis (seven definite and one probable; one early, one late, and six very late) were noticed in the SES group versus three cases (3%, one definite and two possible; all very late) in the BMS group (p=0.21). CONCLUSIONS: The results of the present study show that the documented superior short-term angiographic and clinical results of SES in patients with total coronary occlusions are maintained during long-term 5-year follow-up as compared with BMS. On the other hand, there is a trend to a higher stent thrombosis rate in the SES group. PMID: Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, Chaturvedi N, Persson F, Desai AS, Nicolaides M, Richard A, Xiang Z, Brunel P, Pfeffer MA; ALTITUDE Investigators. [Dunselman PH et al...] Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med Dec 6;367(23): Epub 2012 Nov 3. BACKGROUND: This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for Cardiologie 24