Do statins influence the prognostic impact of non-sustained ventricular tachycardia after ST-elevation myocardial infarction?
Herbert Lorenz1,
Claus Jünger1,
Karlheinz Seidl1,
Anselm Gitt1,
Steffen Schneider1,
Rudolf Schiele1,
Harm Wienbergen1,
Ralph Winkler1,
Martin Gottwik2,
Wolfram Delius3,
Jochen Senges1 and
Bernhard Rauch1,*
1Institut für Herzinfarktforschung, Klinikum der Stadt Ludwigshafen, Bremserstr. 79, D-67063 Ludwigshafen am Rhein, Herzzentrum Ludwigshafen, Germany
2Klinikum Nürnberg Süd, Kardiologie, Nürnberg, Germany
3Städtisches Krankenhaus München-Bogenhausen, Germany
Received 26 July 2004; revised 17 December 2004; accepted 23 December 2004; online publish-ahead-of-print 23 February 2005.
* Corresponding author. Tel: +49 621 5032850; fax: +49 621 5032882. E-mail address: rauchb{at}klilu.de
 |
Abstract
|
---|
Aims The study evaluates the effect of statin therapy on the prognostic impact of non-sustained ventricular tachycardia (NSVT) occurring after acute ST-elevation myocardial infarction (STEMI).
Methods and results From the German Acute Coronary Syndrome Registry (ACOS), 3137 patients with STEMI and in-hospital Holter monitoring were analysed. Three hundred and forty-six (11.0%) patients had NSVT. When compared with patients with no documented NSVT, patients with NSVT were older, more often had myocardial infarction in their history, diabetes mellitus, and an ejection fraction <40%. Regarding frequency of drug application, medication at discharge did not (beta-blockers, ACE-inhibitors, amiodarone) or only slightly (acetylsalicylic acid, statins, and sotalol) differ between both groups. Multivariable analysis of 1 year mortality, adjusted for age, gender, diabetes, reperfusion therapy, ejection fraction <40%, and beta-blocker therapy showed the following results: In patients without statin treatment and no NSVT, 1 year mortality after STEMI was 9.2%, but increased to 25.0% [odds ratio (OR) 3.02; 95% confidence interval (CI) 1.476.20], if NSVT were present. In patients on statin treatment and no NSVT, 1 year mortality was only 3.2%, and in the presence of NSVT 1 year mortality was not significantly increased anymore (5.3%; OR 1.03; 95% CI 0.551.92).
Conclusion After STEMI, only in patients not on statin treatment, the occurrence of NSVT is associated with a significant and marked increase in 1 year mortality.
Key Words: ST-elevation myocardial infarction Statin Non-sustained ventricular tachycardia Prognosis Risk stratification Pleiotropic effect
 |
Introduction
|
---|
The prognostic impact of non-sustained ventricular tachycardia (NSVT) after ST-elevation myocardial infarction (STEMI) under the condition of modern pharmacological treatment including beta-blockers and statins is controversial.16 As statins have been proven to be very effective in reducing mortality rates after myocardial infarction,79 association of NSVT with adverse outcome after STEMI could be influenced by these agents.
The beneficial effect of statins in patients after myocardial infarction has primarily been attributed to lowering of blood cholesterol and thereby attenuating the progression of arteriosclerosis. However, recent data suggest that the beneficial effects of statins may extend to mechanisms beyond cholesterol reduction.1013 These pleiotropic effects include improvement of endothelial function,14,15 inhibition of platelet function1618 and smooth muscle cell proliferation,19,20 enhancing stability of arteriosclerotic plaques,21,22 and attenuating vascular inflammation.2224 There is evidence that many of these effects are the result of reduced synthesis of isoprenoid intermediates of the cholesterol biosynthetic pathway, which serve as lipid attachments for intracellular signalling molecules, thereby affecting various signal transduction pathways.19,25,26 By changing signalling pathways and by modifying the cholesterol/phospholipid ratio in cellular plasma membranes, the beneficial prognostic effect of statins may also result from a favourable modulation of the autonomic nervous system and/or from an increased electrical stability of myocytes. Recent data support this hypothesis, as rosuvastatin has been shown to improve heart rate and blood pressure variability in genetically dyslipidaemic mice,27 simvastatin has been shown to normalize autonomic neural control in experimental heart failure,28 pravastatin has been shown to reduce ventricular late potentials and ventricular arrhythmias in patients with acute myocardial infarction,29 and finally lipid-lowering drug therapy (mostly statins) has been shown to be associated with a reduced probability of recurrent ventricular tachycardias in patients with implantable defibrillators.30
On the basis of the prospective multi-centre Acute Coronary Syndrome Registry (ACOS), the present study therefore evaluates the hypothesis that statin therapy may attenuate the potential adverse prognostic association of NSVT documented in patients after STEMI.
 |
Methods
|
---|
ACOS registry
ACOS is a prospective, multi-centre, observational study on current treatment of acute coronary syndromes (STEMI, non-STEMI, and unstable angina pectoris) in Germany. Patients were recruited from 155 hospitals throughout Germany within the period from June 2000 to December 2002. Every participating centre was committed by written consent to include every consecutive patient with ACOS. Written informed consent was obtained from all patients before participation in the registry. There were no further exclusion criteria.
The present study is an analysis of pre-specified, consecutive patients with STEMI and Holter monitoring during the initial hospital stay, who were discharged alive and either received or did not receive statins at discharge. Until 31 December 2003, a total of 3137 patients with STEMI, complete follow-up, and Holter monitoring were included in the study (Figure 1). The decision for performing Holter monitoring was at the discretion of the treating physician.
Data processing
All data were centrally processed in the data processing centre of the Heart Centre Ludwigshafen. Demographic data, patients history, procedural, outcome, and follow-up data were recorded using four case report forms. The first form recorded the data necessary for diagnosis and specification of the acute coronary syndrome (symptoms, electrocardiography, and cardiac enzymes). The second form included the patient's history (concomitant disease and previous cardiovascular events) and acute therapy (medication, coronary angiography, and reperfusion therapy). Case report form three included elective diagnostic and therapeutic procedures (echocardiography, stress-test, Holter monitoring, and medication) and clinical events until discharge of the patient. Evaluation of Holter monitoring was decentralized and performed in each participating centre. Source data verification was performed by comparison of the registry data with hospital records in randomly selected patients in 20 randomly selected participating centres.
With respect to therapeutic interventions, each participating centre was strongly advised to follow the actual national and international guidelines. On the basis of this advice, medical treatment, including statin treatment, was at the discretion and responsibility of the treating physician. The individual reasons for not treating patients with statins have not been asked in the registry.
Follow-up was centrally achieved 12±1 months after inclusion of the patient by the data processing centre of the Heart Centre Ludwigshafen. Members of the data processing centre contacted the study patients by telephone and completed the follow-up questionnaire (case report form four). Follow-up included documentation of symptoms, clinical events, medication, and rehabilitation during the follow-up period. If patients died during follow-up, death was confirmed by family members and additionally by either the family doctor or the local authorities.
Diagnostic procedures
For Holter monitoring, at least an 18 h continuous registration was required and mean heart rate, total number of ventricular beats, and total number of ventricular tachycardias had to be registered in the corresponding case report form. NSVT was defined as three or more consecutive premature ventricular beats with a rate of more than 100 beats per minute. Left ventricular function was measured by angiography (view: 30° right anterior oblique) or semi-quantitatively by echocardiography (four-chamber view).
STEMI was diagnosed in the presence of one of the following criteria: (i) persistent angina pectoris for
20 min plus ST-segment elevation of
1 mm in two or more standard leads or
2 mm in two or more continuous precordial leads, (ii) persistent angina pectoris for
20 min plus the presence of a left bundle branch block. Diagnosis was later confirmed by the increase of cardiac enzymes to more than twice the upper normal limit.
Stroke was defined as the occurrence of persistent specific neurological deficits irrespective of the aetiology.
Statistical methods
The aim of the study was to investigate the association of NSVT with adverse prognosis after STEMI under the conditions of modern medical treatment. The second step was to test the hypothesis based on recent scientific data that statins may influence this association.
Absolute numbers, per cent, mean, and standard deviation were computed to describe the patient population. Categorical variables were compared using the
2 or Fisher's exact test and continuous variables by using Wilcoxon rank-sum test. Evaluating the baseline characteristics, P-values were only used in a descriptive way to show differences among the four groups under investigation (Tables 1 and 2).
View this table:
[in this window]
[in a new window]
|
Table 1 Baseline characteristics of patients after STEMI either presenting with NSVT during Holter monitoring or not
|
|
Multiple logistic regression analysis was used to compare clinical outcome in the different groups by calculating the odds ratio (OR) and the 95% confidence interval (CI). In this analysis, adjustment was performed for the following variables: age, gender, diabetes mellitus, reperfusion therapy, ejection fraction <40%, and beta-blocker therapy at discharge. These variables were selected according to their clinical relevance and potential impact on long-term prognosis, as shown by earlier studies. To determine whether the model was linear in the logit for continuous variables, a method of designing variables described by Hosmer and Lemeshow31 was used. Interactions among the variables statin therapy and NSVT were checked in the multivariable model.
KaplanMeier curves were used to describe differences in the survival rates between the groups. The differences between survival curves were assessed by a log-rank test. A P-value <0.05 was considered to be statistically significant. All P-values are the results of two-tailed tests. The tests were performed using the SAS© statistical package, version 8.02 (SAS Institute, Cary, NC, USA).
 |
Results
|
---|
From the 3137 patients included in the study, 346 (11.0%) had NSVT documented by in-hospital Holter monitoring (Figure 1). The number of NSVT, as documented by Holter monitoring, in this group exhibited a large variation ranging from one episode in 25% of cases to a maximum of 900 episodes in one case (median: 2 NSVT; lower quartile: 1 NSVT; upper quartile: 5 NSVT).
Table 1 shows the baseline characteristics of patients with and without NSVT either under statin therapy or not. In general, patients with NSVT were older (67.0±12.3 vs. 63.4±12.6 years, P</0.0001), more often had myocardial infarction in their history (20.5 vs. 11.3 %, P</0.0001), had an ejection fraction <40% (33.4 vs. 19.9 %, P</0.0001), and had atrial fibrillation slightly more often (7.2 vs. 4.8%, P=0.048) at admission.
At discharge, 78.0% of the patients with documented NVST and 82.8% of the patients without NSVT were on statin therapy (P=0.027). Distribution of the various types of statins given at hospital discharge was as follows: atorvastatin, 44.3%; simvastatin, 34.7%; pravastatin, 10.2%; cerivastatin, 4.0%; fluvastatin, 3.7%; lovastatin, 3.1%. The other medication at discharge is given in Table 2.
Univariable analysis of the total population showed that patients with STEMI and documented NSVT had increased mortality during follow-up (Figure 2). After multivariable analysis adjusted for age, gender, diabetes, early reperfusion, ejection fraction <40%, statin therapy, and beta-blocker therapy, there was only a trend of NSVT being associated with an adverse prognosis (1 year mortality in patients with STEMI plus NSVT vs. patients without NSVT: OR 1.50; 95% CI 0.972.34).

View larger version (10K):
[in this window]
[in a new window]
|
Figure 2 KaplanMeier curve of deaths occurring during the 1-year follow-up after hospital discharge from acute STEMI (patients without NSVT=upper curve; patients with NSVT=lower curve). See online supplementary material for a colour version of this figure.
|
|
When total population was divided in the two groups of patients either receiving or not receiving statins, in the non-statin group NSVT was associated with a marked, almost three-fold increase of 1 year mortality (Figure 3A). In patients receiving statin therapy, 1 year mortality was significantly reduced; in addition, the association of NSVT with adverse prognosis could no longer be observed (Figure 3B, see Supplementary material online).

View larger version (13K):
[in this window]
[in a new window]
|
Figure 3 KaplanMeier survival curves of patients either having NSVT documented during Holter monitoring (solid line) or not (dotted line), and either being on statin treatment at discharge (right) or not (left). See online supplementary material for a colour version of this figure.
|
|
Multivariable analysis of 1 year mortality adjusted for age, gender, diabetes, early reperfusion, ejection fraction <40%, and chronic beta-blocker therapy confirmed documented NSVT after STEMI being associated with a significant increase of 1 year mortality in the group of patients not on statin therapy, whereas statin therapy was associated with a decrease of mortality regardless of the presence or absence of NSVT. Furthermore, if patients were on statin therapy, NSVT were not associated with adverse long-term prognosis anymore (Table 3). To formally assess the hypothesis that statin treatment influences the prognostic impact of NSVT after STEMI (1 year all-cause mortality), the interaction term between statin treatment and NSVT was determined and shown to be statistically significant (OR 0.39; 95% CI 0.150.98; P=0.047).
View this table:
[in this window]
[in a new window]
|
Table 3 Multivariable analysis of 1 year all-cause mortality of patients after acute STEMI, adjusted for age, gender, diabetes, reperfusion, ejection fraction <40%, and chronic beta-blocker therapy
|
|
Statin therapy was also associated with a reduced rate of non-fatal major adverse events (sum of non-fatal re-infarction and non-fatal stroke) during follow-up, but these changes did not reach the level of significance [patients with documented NSVT: statin () vs. statin (+) 10.0/6.7%, P=0.42; patients without NSVT: statin () vs. statin (+) 6.3/4.2%, P=0.07].
 |
Discussion
|
---|
The present study shows the occurrence of NSVT after STEMI being associated with an increased long-term mortality. However, this adverse effect only applies for patients not on statin therapy. Statins significantly reduce long-term mortality irrespective of the absence or presence of NSVT; moreover, the data suggest that statins are able to markedly attenuate the association of NSVT with adverse outcome after STEMI.
The prevalence of NSVT after STEMI in this study is in the same range as reported in previous studies.1,2,4,32 Patients with or without NSVT did not largely differ in discharge medication including ACE-inhibitors, beta-blockers, and statins. In both groups, only a minority of the patients obtained specific anti-arrhythmic drugs at discharge. As expected, however, patients with NSVT more often had previous myocardial infarction and severely reduced left ventricular function. In multivariable analysis, taking these parameters into account, only NSVT was associated with a trend to adverse prognosis. Indeed, the independent prognostic value of NSVT in the era of modern treatment of myocardial infarction including thrombolysis, PCI, beta-blockers, and statins is controversial and has been questioned previously.24,33,34
The situation completely changes if the prognostic value of NSVT is evaluated within the subgroups of patients either receiving or not receiving statins. Whereas in patients without statin treatment the occurrence of NSVT was associated with an almost three-fold increase of 1 year mortality, NSVT had no independent predictive value on long-term mortality anymore, if patients received statins at discharge.
The present study only investigates all-cause mortality after STEMI, and the data of the ACOS registry do not allow the differentiation of the individual cause of death on a reliable basis. As differences in the classification of death adopted in different recent trials and inter-observer discordance may complicate classification,35 the use of total mortality has been advocated as the most reliable endpoint in myocardial infarction studies.36 Still, it is well known that a significant portion of the patients, who die within 1 year after STEMI, die from sudden death.36 It may therefore be suggested that one of the beneficial mechanisms of statins could be to rapidly affect signalling pathways in cell membranes of the myocardium and/or the autonomic nervous system, thereby protecting patients from life-threatening arrhythmias.25,26 This assumption would be in line with recent data showing statins to improve autonomic neural control and increase electrical stability of the myocardium.2729 In addition, in patients with coronary artery disease and implanted cardioverter defibrillator lipid-lowering therapy (the majority of patients receiving statins) was associated with a reduction of the recurrence of ventricular tachycardia.30 However, further investigations are necessary to confirm the clinical significance of these observations and to clarify the potentially underlying mechanisms. Furthermore, other protective mechanisms have to be additionally taken into account as improvement of endothelial function has also been shown to occur early after starting statin therapy.14
In the present study, in both groups (NSVT vs. no NSVT) statin therapy was associated with a reduced number of non-fatal major adverse events (re-infarction and/or stroke) within 1 year of follow-up, but this effect did not reach the level of significance. Lack of significance could be the result of the relatively small number of non-fatal adverse events during this time period. Furthermore, with regard to the group of patients with NSVT, the subgroups either receiving or not receiving statins were small. Prolongation of the follow-up period would be necessary to get clarification.
 |
Study limitations
|
---|
The present investigation is not a randomized, controlled study evaluating the effect of statins on patients with STEMI and NSVT. However, randomization of these patients in two groups either receiving or not receiving statins is not actually possible for ethical reasons. Therefore, the present prospective and well-defined registry appears to be an acceptable way for evaluation of the therapeutic effect of statins in certain subgroups. Moreover, this study included all patients with STEMI as presented in clinical practice, suggesting a sufficient clinical impact of the results.
In the ACOS registry, performance of in-hospital Holter monitoring was at the discretion of the treating physician. This could result in some selection bias, which, however, does not necessarily affect the presented results and conclusions. For example, if patients with pre-discharge Holter monitoring represent a group of special risk, this would even increase the clinical relevance of the data.
Another limitation of the study is that evaluation has been made on an intention-to-treat basis, taking into account only the discharge medication. However, even if statin treatment is discontinued in a part of the patients during follow-up, the present results still highlight the importance of statin treatment in the early period after STEMI and its special impact on prognosis in patients presenting with NSVT.
Taking into account these limitations, data of the present study have to be considered as hypothesis generating until confirmation by future investigations.
 |
Conclusion
|
---|
In conclusion, after STEMI, it is only in patients not on statin treatment that the occurrence of NSVT is associated with a significant and marked increase in 1 year mortality. Under statin treatment, however, NSVT is not associated with an adverse long-term prognosis, suggesting that statins may have an additional effect beyond cholesterol lowering and plaque stabilization, which may be associated with a stabilization of myocardium against pro-arrhythmic events.
 |
Supplementary material
|
---|
Supplementary material is available at European Heart Journal online.
 |
Acknowledgements
|
---|
The ACOS registry has been supported by MSD SHARP and DOHME GmbH. We thank Elke H. Becker-Wördenweber for her excellent technical assistance.
 |
Appendix
|
---|
The following list presents the participants of the ACOS-registry:
E. Altmann, Krankenhaus Dresden-Friedrichstadt, Dresden; O. Altmann, Diakonissenkrankenhaus, Dresden; G. Weber, Kreiskrankenhaus Pirna, Pirna; G. Hempel, Kreiskrankenhaus Bautzen, Bautzen; H. Klinger, U. Scholze, Diakonissenkrankenhaus Emmaus, Niesky; W.P. Sommer, Kreiskrankenhaus Weisswasser, Weisswasser; Park, Klinikum Hoyerswerda, Hoyerswerda; Schuler, Herzzentrum Leipzig, Leipzig; H.-G. Olbrich, KH St Elisabeth und St Barbara, Halle; D. Heibutzki, Kreiskrankenhaus Köthen, Köthen; H. Kramer, Kreiskrankenhaus Aschersleben, Aschersleben; J. Truckenbrodt, Kreiskrankenhaus, Zeitz; R. Schinke, Kreiskrankenhaus, Bitterfeld; S. Rosocha, Städt. Klinikum Dessau, Dessau; F. Meier, Kreiskrankenhaus, Rudolstadt; Schellner, DRK-Krankenhaus Rabenstein, Chemnitz; E. Pleger, Krankenhaus Prenzlauer Berg, Berlin; H. Kuckuck, Vivantes Wenckebach Krankenhaus, Berlin; K.-P. Schüren, Auguste-Viktoria-Krankenhaus, Berlin; O.J. Titlbach, Krankenhaus Hellersdorf, Berlin; J. Beckert, Caritas Kliniken Pankow, Berlin; E. Fleck, Deutsches Herzzentrum Berlin, Berlin; E. Franz, St Josefskrankenhaus, Potsdam; M. Oeff, Staedtisches Klinikum, Brandenburg ad Havel; U. Burchard, Klinikum Frankfurt (Oder), Frankfurt/Oder; H. Koch, Krankenhaus Beeskow, Beeskow; H. Barkhausen, Asklepios-Klinik, Parchim; G. Gerke, Kreiskrankenhaus Buxtehude, Buxtehude; G. Lockert, Elbe Klinikum Stade; V. Sill, Allgemeines Krankenhaus Wandsbek, Hamburg; Freudenthaler, Maeder, Gützow, Ostholstein-Kliniken, Eutin; A. Jakobeit, S. Kaminsky, Ostholstein-Kliniken, Oldenburg; H. Greiner-Leben, Städt. Krankenhaus Wismar, Wismar; H.-G. Lahrtz, B. Gerrard, Kreiskrankenhaus Eckernförde, Eckernförde; M. Kentsch, Krankenhaus Itzehohe, Itzehohe; T. Schleiffer, St Willehad-Hospital, Wilhelmshaven; A. Heisel, Reinhard-Nieter-Krankenhaus, Wilhelmshaven; W. Josephs, Kreiskrankenhaus Norden, Norden; B. Pensel, Kreiskrankenhaus Aurich, Aurich; W. Peiffer, Ammerland-Klinik, Westerstede; J. Jahn, Borromäus-Hospital, Leer; J. Potratz, Diakoniekrankenhaus, Rotenburg; G. Inselmann, Stadtkrankenhaus Cuxhaven, Cuxhaven; U. Sander, DRK-Krankenhaus am Buergerpark, Bremerhaven; H.-J. Engel, Hegeler, Zentralkrankenhaus Links der Weser, Bremen; B. Ruehlmann, Zentralkrankenhaus Bremen Nord, Bremen; A. Jacobs, Heidekreis-Klinikum GmbH, Soltau; K.-H. Wiese, Heidekreis-Klinikum GmbH, Walsrode; B. Martin, DRK-Krankenhaus, Hannover; A. Hepp, Vincenz-Krankenhaus, Hannover; U. Grommas, Städtisches Krankenhaus, Wolfenbüttel; J. Molling, H. Klein, Universitätsklinikum Magdeburg, Magdeburg; E. Vester, Evang. Krankenhaus, Duesseldorf; Lüthen, Marienhospital, Duesseldorf; K.-H. Konz, Krankenhaus Maria Hilf II GmbH Franziskushaus, Moenchengladbach; N. Ludwig, Kamillianer Krankenhaus Moenchengladbach GmbH, Moenchengladbach; K. Emmrich, Klinikum Niederberg, Velbert; H. Loellgen, Klinikum Burger Strasse, Remscheid; R. Lemke, Krankenhaus Bethanien, Dortmund; S. Rebhuhn, Katholisches Krankenhaus, Dortmund; J. Barmeyer, Bergmannsheil-Uniklinik, Bochum; F.-J. Wittstamm, Kliniken Essen Mitte, Essen; B. Koslowski, Kliniken Essen-Sued Ev. KH Essen-Werden; U. Loos, Philip, Knappschaftskrankenhaus, Recklinghausen; P.-G. Auer, St Josef Hospital, Gelsenkirchen; E. Wobser, Knappschaftskrankenhaus Bergmannsheil, Gelsenkirchen; K.W. Heinrich, Evangelisches u. Johanniter Klinikum, Duisburg; G. Neumann, Kath. Klinikum Duisburg, Duisburg; H.G. Klues, Klinikum Krefeld, Krefeld; P. Kleine-Katthöfer, St Franziskus-Hospital, Münster; P. Baumgart, Clemenshospital GmbH, Muenster; T. Dorsel, Josephs-Hospital, Warendorf; N. Treese, Marienhospital, Osnabrück; J. Thale, Klinikum Osnabrueck, Osnabrueck; J. Thale, Schuechtermann-Klinik, Bad Rothenfelde; M. Ritter, St Elisabeth-Hospital von Bodelschwingh Krankenhaus, Ibbenbueren; H.-J. Deutsch, St Katharinen-Hospital, Frechen; D. Mitrenga, Krankenhaus der Augustinerinnen, Koeln; C. Witthoeft, Eduardus-Krankenhaus, Koeln; P. Sawitzki, St Franziskus-Hospital, Koeln; Ch. Pohl, St Elisabeth-Krankenhaus GmbH, Koeln; N. Busch, Knappschafts-Krankenhaus Bardenberg, Wuerselen; J. Kindler, Kreiskrankenhaus Marienhoehe gGmbH, Wuerselen; H. Schmitt, Bethlehem-Krankenhaus, Stolberg; C.-J. Schuster, St Antonius-Hospital, Eschweiler; D. Gulba, Krankenhaus Dueren, Dueren; P. Stollte, Universitaetsklinik Bonn, Bonn; H. Kahles, Marien-Hospital, Euskirchen; J. Cailloud, Evang. Elisabeth-Krankenhaus, Trier; K.-E. Hauptmann, Krankenhaus der Barmherzigen Brüder, Trier; T. Eisenhauer, Städt. Klinikum Kemperhof, Koblenz; G. Lauck, DRK-Krankenhaus Neuwied, Neuwied; R. Schräder, Krankenhaus St Markus, Frankfurt/Main; Ch. Hamm/Frau Reuschling, Kerckhoff Forschungszentrum GmbH, Bad Nauheim; H. Klepzig, Staedt. Kliniken Offenbach, Offenbach; H. von Lilienfeld-Toar, Mainz-Kinzig-Klinik gGmbH, Gelnhausen; W. Kasper, St Josefs-Hospital, Wiesbaden; H.J. von Mengden, Stadtkrankenhaus Ruesselsheim, Ruesselsheim; S. Sen, Staedtisches Krankenhaus Frankfurt-Hoechst, Frankfurt/Main; G. Görge, Klinikum Saarbrücken, Saarbrücken; Kampschulte, St Elisabeth-Krankenhaus, Zweibrücken; A. von Bierbrauer, Krankenhaus Neunkirchen, Neunkirchen; H. J. Gabriel, St Johannes Krankenhaus, Landstuhl; Setz, St Josefs Krankenhaus Dahn, Dahn; J. Senges, Medizinische Klinik B, Klinikum Ludwigshafen, Ludwigshafen/Rhein; H. Weiss, St Marien- und St Annastiftskrankenhaus, Ludwigshafen/Rhein; H. Ramisch, Evangelisches Krankenhaus Bad Dürkheim; F. Niedermeier, Städt Krankenhaus Frankenthal, Frankenthal; A. Horsch, Stiftungs-Krankenhaus Speyer, Speyer; A. Weizel, Diakonie-Krankenhaus, Mannheim; E. Chorianopoulos, Theresien-Krankenhaus, Mannheim; R. Hehrmann, Diakonissenkrankenhaus, Stuttgart; U. Sächtem, Robert-Bosch-Krankenhaus, Stuttgart; U. Solzbach, Ostalbklinikum Aalen, Aalen; M. Leschke, Staedtische Kliniken Klinik fuer Innere Medizin, Esslingen; J. Manthey, Kreiskrankenhaus am Plattenwald, Bad Friedrichshall; B. D. Gonska, St Vincentius-Krankenhaus, Karlsruhe; H.-J. Augustin, Stadtklinik Baden-Baden, Baden-Baden; C. Beyerlein-Buchner, Asklepios Südpfalz, Germersheim; K. Weindel, Vinzentius-Krankenhaus Landau; A. Reck, Kreiskrankenhaus, Annweiler; W. Jung, Klinikum, Villingen-Schwenningen; H. Zeif, Herz-Zentrum Bodensee GmbH, Konstanz; G. Müller-Esch, Klinikum, Konstanz; B. Steinke, Kreiskrankenhaus Rottweil; G. Hauf, Herzzentrum, Bad Krozingen; R. Cardoso, Krankenhaus Spitalfond, Waldshut-Tiengen; V. Klauss, Klinikum Innenstadt der LMU, Muenchen; T. Graf von Arnim, Rotkreuz-Krankenhaus, München; M. Roth, Stiftsklinikum Augustinum, Muenchen; C. Spes, Städt. Krankenhaus Neuperlach, München; W. Delius, Staedt. Krankenhaus Muenchen-Bogenhausen; K. Schlotterbeck, Kreiskrankenhaus Traunstein, Traunstein; Bruckmaier, Kreiskrankenhaus, Trostberg; G. Pilz, Kardiologie Agatharied, Hausham; R. Brueckl, Kreisrankenhaus Landshut-Achdorf, Landshut; A. Dietz, Kreiskrankenhaus Burghausen; K. Hahn, Kreiskrankenhaus Altötting, Altötting; Pfafferott, Klinikum Ingolstadt, Ingolstadt; K.G. Mackes, Kreiskrankenhaus Freising, Freising; H. L. Schneider, Kreiskrankenhaus Ebersberg, Ebersberg; F. Seidel, Klinikum Kempten, Kempten; A. Ueberreiter, Klinikum Ostallgaeu Kaufbeuren, Kaufbeuren; M. Gottwik, Klinikum Nuernberg Sued, Nürnberg; W. Spitzer, Kreiskrankenhaus Neustadt/Aisch; C. Schultes, Kreiskrankenhaus Eschenbach; Rinke, Kreiskrankenhaus, Wörth; J. Jehle, Klinikum St Elisabeth Straubing GmbH, Straubing; L. Kammermeyer, Klinikum Deggendorf, Deggendorf; W. Mäurer, Klinikum Bayreuth, Bayreuth; J. Brachmann, Klinikum Coburg gGmbH, Coburg; G. Ertl, Universitaetsklinikum Wuerzburg, Wuerzburg; W. Kestel, Kreiskrankenhaus, Lohr am Main; H.-D. Bundschu, Caritas-Krankenhaus GmbH, Bad Mergentheim; I. Aßmann, Klinikum Erfurt GmbHF, Erfurt; Münscher-Paulig, Hufeland-Krankenhaus, Bad Langensalza.
 |
References
|
---|
- Maggioni AP, Zuanetti G, Franzosi MG et al. On behalf of the GISSI-2 investigators. Prevalence and prognostic significance of ventricular arrhythmias after acute myocardial infarction in the fibrinolytic era. Circulation 1993;87:312322.[Abstract]
- Drögemüller A, Seidl K, Schiele R et al. for the MITRA Study Group. Prognostic value of non-sustained ventricular tachycardias after acute myocardial infarction in the thrombolytic era: importance of combination with frequent premature beats. Z Kardiol 2003;92:164172.[CrossRef][ISI][Medline]
- Giani P, Avanzini F, Bagliani G et al. The predictive value for major arrhythmic events of ventricular arrhythmias, particularly non-sustained ventricular tachycardias, in the subacute phase of a fibrinolyzed infarct. An analysis of GISSI-2 data. G Ital Cardiol 1995;25:7787.[Medline]
- Hohnloser SH, Klingenheben TH, Zabel M et al. Prevalence, characteristics and prognostic value during long-term follow-up of non-sustained ventricular tachycardia after myocardial infarction in the thrombolytic era. J Am Coll Cardiol 1999;33:18951902.[CrossRef][ISI][Medline]
- Buxton AE, Lee KL, DiCarlo L et al. Non-sustained ventricular tachycardia in coronary artery disease: relation to inducible sustained ventricular tachycardia. MUSTT Investigators. Ann Intern Med 1996;125:3539.[Abstract/Free Full Text]
- Senges JC, Becker R, Schreiner KD et al. Variability of Holter electrocardiographic findings in patients fulfilling the non-invasive MADIT criteria. Multicenter Automatic Defibrillator Implantation Trial. PACE 2002;25:183190.[ISI][Medline]
- Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:13831389.[CrossRef][ISI][Medline]
- Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels: the Long-Term Intervention With Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998;339:13491357.[Abstract/Free Full Text]
- Sacks FM, Pfeffer MA, Moye LA et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial Investigators. N Engl J Med 1996;335:10011009.[Abstract/Free Full Text]
- Vaughan CJ, Murphy MB, Buckley BM. Statins do more than just lower cholesterol. Lancet 1996;348:10791082.[CrossRef][ISI][Medline]
- Massy ZA, Keane WF, Kasiske BL. Inhibition of the mevalonate pathway: benefits beyond cholesterol reduction? Lancet 1996;347:102103.[CrossRef][ISI][Medline]
- Bellosta S, Ferri N, Bernini F et al. Non-lipid-related effects of statins. Ann Med 2000;32:164176.[ISI][Medline]
- Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methyl coenzyme A reductase inhibitors. Arterioscler Thromb Vasc Biol 2001;21:17121729.[Abstract/Free Full Text]
- O'Driscoll G, Green D, Taylor RR. Simvastatin, a HMG-coenzyme: a reductase inhibitor, improves endothelial function within 1 month. Circulation 1997;95:11261131.[Abstract/Free Full Text]
- Mital S, Zhang X, Zhao G et al. Simvastatin upregulates coronary vascular endothelial nitric oxide production in conscious dogs. Am J Physiol 2000;279: H2649H2657.[ISI]
- Huhle G, Abletshauser C, Mayer N et al. Reduction of platelet activity markers in type II hypercholesterolemic patients by a HMG-CoA-reductase inhibitor. Thromb Res 1999;95:229234.[CrossRef][ISI][Medline]
- Schrör K. Platelet reactivity and arachidonic acid metabolism in type II hyperlipoproteinaemia and its modification by cholesterol-lowering agents. Eicosanoids 1990;3:6773.[ISI][Medline]
- Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. J Am Med Assoc 1998;279:16431650.[Abstract/Free Full Text]
- Laufs U, Marra D, Node K, Liao JK. 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors attenuate vascular smooth muscle proliferation by preventing rho GTPase- induced down-regulation of p27(Kip1). J Biol Chem 1999;274:2192621931.[Abstract/Free Full Text]
- Yang Z, Kozai T, van der Loo B et al. HMG-CoA reductase inhibition improves endothelial cell function and inhibits smooth muscle cell proliferation in human saphenous veins. J Am Coll Cardiol 2000;36:16911697.[CrossRef][ISI][Medline]
- Koh KK. Effects of statins on vascular wall: vasomotor function, inflammation, and plaque stability. Cardiovasc Res 2000;47:648657.[CrossRef][ISI][Medline]
- Aikawa M, Rabkin E, Sugiyama S et al. An HMG-CoA reductase inhibitor, cerivastatin, suppresses growth of macrophages expressing matrix metalloproteinases, and tissue factor in vivo and in vitro. Circulation 2001;103:276283.[Abstract/Free Full Text]
- Walter DH, Fichtlscherer S, Britten MB et al. Statin therapy, inflammation and recurrent coronary events in patients following coronary stent implantation. J Am Coll Cardiol 2001;38:20062012.[CrossRef][ISI][Medline]
- Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1999;100:230235.[Abstract/Free Full Text]
- Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vasc Biol 2001;21:17121719.[Abstract/Free Full Text]
- Van Aelst L, D'Souza-Schorey C. Rho GTPases and signalling networks. Genes Dev 1997;11:22952322.[Free Full Text]
- Pelat M, Dessy C, Massion P et al. Rosuvastatin decreases caveolin-1 and improves nitric oxide-dependent heart rate and blood pressure variability in apolipoprorein E/ mice in vivo. Circulation 2003;107:24802486.[Abstract/Free Full Text]
- Pliquett RU, Cornish KG, Peuler JD, Zucker IH. Simvastatin normalizes autonomic neural control in experimental heart failure. Circulation 2003;107:24932498.[Abstract/Free Full Text]
- Kayikcioglu M, Can L, Evrengul H, Payzin S, Kultursay H. The effect of statin therapy on ventricular late potentials in a myocardial infarction. Int J Cardiol 2003;90:6372.[CrossRef][ISI][Medline]
- Mitchell LB, Powell JL, Gillis AM, Kehl V, Hallstrom AP, and the AVID Investigators. Are lipid-lowering drugs also antiarrhythmic drugs? An Analysis of the Antiarrhythmic Versus Implantable Defibrillators (AVID) Trial. J Am Coll Cardiol 2003;42:8187.[CrossRef][ISI][Medline]
- Hosmer DW Jr, Lemeshow S. Applied Logistic Regression. New York: Wiley and Sons; 2000.
- Bigger JT Jr, Weld FM, Rolnitzky LM. Prevalence, characteristics and significance of ventricular tachycardia (three of more complexes) detected with ambulatory electrocardiographic recording in the late hospital phase of acute myocardial infarction. Am J Cardiol 1981;48:815823.[CrossRef][ISI][Medline]
- Bauer A, Gawaz M, Becker R et al. Predictive value of frequency, duration and rate of ventricular salvos in ambulatory ECG for inducibility of sustained ventricular tachycardia. Z Kardiol 2001;90:117183.
- Ellison KE, Hafley GE, Hickey K et al. Effect of beta-blocking therapy on outcome in the Multicenter UnSustained Tachycardia Trial (MUSTT). Circulation 2002;106:26942699.[Abstract/Free Full Text]
- Ziesche S, Rector ST, Cohn JN. Interobserver discordance in the classification of mechanisms of death in studies of heart failure. J Card Fail 1995;1:127132.[CrossRef][Medline]
- Priori SG, Aliot E, Blomstrom-Lundqvist C et al. Task Force ReportTask force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J 2001;22:13741450.[Free Full Text]