Mr Guenter Breithardt,
Reported by Prof. Giuseppe Boriani, Institute of Cardiology, University of Bologna, Italy on behalf of Search-MI investigators (Principal Investigator Prof. Massimo Santini,)
Sudden cardiac death is the leading cause of mortality in European and North-American countries. In March 2002, the results of the North American MADIT-II randomized clinical trial revealed that high-risk post-myocardial infarction patients, selected on the basis of reduced left ventricular ejection fraction, without prior ventricular tachyarrhythmia, exhibited an improved survival in the arm receiving an implantable cardioverter-defibrillator (ICD). This led the cardiology societies of America and Europe (ACC/AHA/ESC) to amend guidelines on the clinical management of patients at risk for sudden cardiac death and to recommend ICD implants for prophylactic indications. Yet, many important clinical questions do not lend themselves to clinical trials, and recent guidelines state that such data could be obtained from "additional studies with broad objectives … and additional registry data". In particular, data is needed to increase the knowledge about the treatment effect and efficacy of ICD therapies in different population strata (such as gender, age, history of diabetes, severity of heart failure). Indeed, immediately after the publication of the MADIT-II study results, a debate emerged on the possibility to translate the benefits observed in strictly controlled trial-selected patients to “real world” practice. SEARCH-MI is a multicenter registry created in 2002 to prospectively evaluate the arrhythmic rate and ICD interventions in post-infarction patients receiving a prophylactic ICD according to current guidelines. The data now available are derived from an interim analysis on 556 patients all with a follow up of more than 70 days. The patients (mean age 66 years) were implanted with various types of ICDs (single-chamber in 50%, dual-chamber in 25%, biventricular in 25%). It is noteworthy that a relevant proportion of enrolled patients (25%) received a device for cardiac resynchronization therapy, in accordance with the scientific contributions of COMPANION and CARE-HF trials. In the patients enrolled in Search MI, mean left ventricular ejection fraction was 26±6% (23±6% in MADIT II), and NYHA class distribution was the following: NYHA I in 9%, II in 46%, III in 43% and IV in 2%, indicating more severe symptoms in comparison with MADIT II (NYHA class I in 35%, II in 35%, III in 25% and IV in 5%, respectively). The results at a mean follow up of 17 months showed that, overall, the incidence of first appropriate ICD therapy was 20%, similar to MADIT II. In detail, 18% and 26% of patients at one and two years, respectively, received at least an appropriate treatment for ventricular tachyarrhythmia (17% and 27%, respectively, in MADIT II study). Moreover, overall mortality in Search-MI was also similar to MADIT II. The contribution of this registry appears to be important. Since appropriate shocks and overall mortality observed in Search MI were comparable with the MADIT II trial, it appears that the benefits of ICD therapy in high-risk patients with a previous myocardial infarction can be replicated in “real world” routine clinical practice. (Read the related press release )
Discussant report: Breithardt, Guenter (Germany) This survey that enrolled post-myocardial infarction patients between 2002 to 2006, prospectively assessed the incidence of ICD interventions in patients that were considered to be at high-risk of life-threatening ventricular arrhythmias. Based on contemporary guidelines, these patients received an ICD for primary prevention. Patients were followed up to two years. This patient cohort was compared to patients receiving an ICD in the MADIT II trial. View the slides SEARCH-MI patients were comparable to MADIT II patients with regard to mean age, mean ejection fraction, and time from last myocardial infarction to ICD implant. However, SEARCH-MI patients were in higher NYHA classes, had undergone bypass surgery or PCIs less frequently, had more frequent left bundle branch block, less frequently received statins but received more frequently diuretics and beta-blockers compared to MADIT II patients. There was also a tendency towards a higher proportion of patients receiving amiodarone in SEARCH-MI. During follow-up, Kaplan-Meier curves for first ventricular arrhythmia detection and for first appropriate ventricular therapy were amazingly identical between SEARCH-MI and MADIT II. In SEARCH-MI, there were no major differences in the number of episodes detected whether the patients received single or dual chamber devices or CRT (biventricular) ICDs. This also applied to the first appropriate ventricular therapy. Similarly, there were no differences in the proportion of first inappropriate therapies as a function of device type. Also all-cause mortality and sudden death mortality were comparable between the registry data of SEARCH-MI and the data from the randomised ICD group in MADIT II. Thus, the authors concluded that the benefits of primary prevention in post-MI patients appeared to be confirmed also in real world practice. Comment: The benefit of ICD therapy in primary prevention after myocardial infarction has been well documented by prospective randomised clinical trials (MADIT, MADIT II). These data, nevertheless, have created some controversy about indications in real life. Clinical trials mostly represent highly selected patient populations. Therefore, the performance of the ICD in clinical practice in less selected populations is of great interest. The data by SEARCH-MI show that a carefully performed registry can play an important role in documenting the potential beneficial effects of a given therapy in clinical practice. Although the authors had claimed that the intention was to monitor current European primary ICD implantation practices, their data are mostly based on patients from Italy (73 %) and Germany (22 %), whereas the contributions from Austria (1 %) and Israel (3 %) were marginal. Thus, with regard to the great diversity in implantation rates in the various European countries, their claim that these are European data, is not met. This does not distract from the merit of this registry which allows an extrapolation from randomised trial data to clinical practice. The group should be congratulated for having organized and performed this registry that shows, in a contemporary patient population, the benefit of selecting patients long after myocardial infarction for ICD therapy based on low ejection fraction, as originally suggested by the MADIT II trial.
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G. Boriani1, B. Shmidt2, M. Lunati3, G. Botto4, A. Proclemer5, A. Erdogan6, W. Rahue7, M. Russo8, M. Santini8 (1) Institute of Cardiology, University of Bologna, Bologna, Italy (2) Universitatsklinikum, Freiburg, Germany (3) Niguarda Ca Grande Hospital, Milano, Italy (4) S. Anna Hospital, Como, Italy (5) S. M. della Misericordia Hospital, Udine, Italy (6) Klinikum der Justus-Liebig-Universitat, Giessen, Germany (7) S. Maurizio Hospital, Bolzano, Italy (8) S. Filippo Neri Hospital, Roma, Italy
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