CLINICAL RESEARCH: ACUTE MYOCARDIAL INFARCTION
Antiarrhythmic effect of carvedilol after acute myocardial infarction
Results of the Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) trial
John McMurray, MD*,*,
Lars Køber, MD ,
Michele Robertson, BSc ,
Henry Dargie, MB, ChB*,
Wilson Colucci, MD ,
Jose Lopez-Sendon, MD||,
Willem Remme, MD¶,
D. Norman Sharpe, MD# and
Ian Ford, PhD
* Department of Cardiology, Western Infirmary, Glasgow, United Kingdom
Department of Cardiology, Gentoffe University Hospital, Copenhagen, Denmark
Robertson Centre for Biostatistics, University of Glasgow; Glasgow, United Kingdom
Boston University Medical Center, Boston, Massachusetts
|| Department of Cardiology, Hospital University, Madrid, Spain
¶ Sticares Foundation, Rhoon, the Netherlands
# Department of Medicine, University of Auckland, Auckland, New Zealand
Manuscript received June 2, 2003;
revised manuscript received August 26, 2004,
accepted September 2, 2004.
* Reprint requests and correspondence: Prof. John J. V. McMurray, Department of Cardiology, Western Infirmary, Glasgow, G11 6NT, United Kingdom (Email: j.mcmurray{at}bio.gla.ac.uk).
 |
Abstract
|
|---|
OBJECTIVES: Whether beta-blockers reduce atrial arrhythmias and, when added to an angiotensin-converting enzyme (ACE) inhibitor, ventricular arrhythmia is unknown.
BACKGROUND: Ventricular and atrial arrhythmias are common after acute myocardial infarction (AMI) and are associated with a poor prognosis. Angiotensin-converting enzyme inhibitors reduce the incidence of both types of arrhythmia.
METHODS: The antiarrhythmic effect of carvedilol was examined in a placebo-controlled multicenter trial, the Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) study, which enrolled 1,959 patients with reduced left ventricular systolic function after AMI, 98% of whom were treated with an ACE inhibitor.
RESULTS: The incidence of atrial fibrillation/flutter was 53 to 984 (5.4%) in the placebo group and 22 to 975 (2.3%) in the carvedilol group, giving a carvedilol/placebo hazard ratio (HR) of 0.41 (95% confidence interval [CI] 0.25 to 0.68; p = 0.0003). The corresponding rates of ventricular tachycardia/flutter/fibrillation were 38 to 984 (3.9%) and 9 to 975 (0.9%) (HR 0.24, 95% CI 0.11 to 0.49; p < 0.0001).
CONCLUSIONS: Carvedilol has a powerful antiarrhythmic effect after AMI, even in patients already treated with an ACE inhibitor. Carvedilol suppresses atrial as well as ventricular arrhythmias in these patients.
|
Abbreviations and Acronyms
| | ACE = angiotensin-converting enzyme | | AE = adverse event | | AF = atrial fibrillation | | CAPRICORN = Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction trial | | CI = confidence interval | | DIAMOND-MI = Danish Investigations of Arrhythmia and Mortality on Dofetilide-Myocardial Infarction study | | HR = hazard ratio | | MI = myocardial infarction | | SAE = serious adverse event | | TRACE = Trandolapril Cardiac Evaluation study |
|
Cardiac arrhythmias are common early after myocardial infarction (MI) and portend a poor prognosis (1–4). Elevated sympathetic nervous system activity is one contributory mechanism and, by counteracting this, beta-adrenoceptor antagonists may reduce cardiac electrical instability (5–8). Most attention has been paid to ventricular arrhythmias, and these were the focus of previous studies of the antiarrhythmic action of beta-blockers after MI (9–13). It is also recognized, however, that atrial fibrillation (AF) results in a worse outcome after MI, although no placebo-controlled trial has examined whether beta-blockers reduce the risk of atrial arrhythmias in this setting (2,4,14–17).
More recently, angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce both ventricular and atrial arrhythmias in higher risk post-MI patients (18–21). It is not known whether beta-blockers, added to ACE inhibitor treatment, will further reduce arrhythmias in these patients.
The Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) study was a multinational prospective, randomized, event-driven, mortality/morbidity trial carried out in patients with recent acute MI and left ventricular systolic dysfunction (22,23). All patients were expected to be treated with an ACE inhibitor (and 98% were). Patients were blindly allocated to placebo or carvedilol. This analysis describes the effect of carvedilol on the risk of atrial and ventricular arrhythmias.
|
Methods
|
|---|
The CAPRICORN trial.
The design and primary results of the CAPRICORN trial have been described in detail elsewhere (22,23). Briefly, 984 patients were allocated to placebo and 975 were allocated to carvedilol between 3 to 21 days post-MI (mean 10 days) and followed for an average of 1.3 years. All prespecified end points (death and certain types of cardiovascular hospitalization) were adjudicated by a blinded end point committee.
Arrhythmia analysis.
Cardiac arrhythmias were not a prespecified end point in the CAPRICORN trial. This analysis was, therefore, a post-hoc, though blinded, one. One end point committee member (J.M.) reviewed all adverse and serious adverse event reports (AEs and SAEs) without knowing treatment allocation. All events thought to be related to an arrhythmia were assigned to one of the following categories, which were decided upon before the analysis was undertaken:
- Atrial arrhythmias: 1) any report of supraventricular ectopic beats, atrial tachycardia, atrial flutter, AF, or any other "supraventricular tachycardia," excluding sinus tachycardia; 2) AF/atrial flutter only.
- Ventricular arrhythmias: 1) any report of ventricular ectopic beats, ventricular tachycardia, ventricular fibrillation, or ventricular flutter; 2) "malignant" ventricular arrhythmias only (i.e., ventricular tachycardia, ventricular fibrillation, and ventricular flutter).
Arrhythmias were identified and characterized according to the AE narrative, and electrocardiogram confirmation was not available.
Prior arrhythmias.
Information on prior arrhythmias was collected in two ways. Investigators were asked to complete a "medical history" form at the screening visit. This form sought information on prior or ongoing problems. Investigators were also asked to complete a "signs and symptoms" baseline visit form at the time of randomization, designed to identify any changes in the patients' clinical condition from screening. The baseline visit usually occurred on the same date as screening, but could take place later. Because >5% of patients have a previous or ongoing atrial arrhythmia recorded at their screening visit, two sets of analyses were performed. The main analysis used all randomized patients. A separate analysis was carried out in the subset of patients without a history of atrial arrhythmias. A similar secondary analysis was performed for patients with prior or recent ventricular arrhythmias.
Combined outcomes.
To take account of the issue of "competing risks," in relation to the different survival rates in the two treatment groups (whereby deceased patients cannot be at risk of an arrhythmia), we also examined a number of combined outcomes, taking account of death or an arrhythmia.
Statistical analysis.
All analyses were carried out on an intention-to-treat basis. All outcomes were analyzed using a time-to-first-event approach. The statistical significance of treatment comparisons was based on the log-rank test. Hazard ratios (HR) and 95% confidence intervals (CIs) were derived from the fitting of Cox proportional hazards regression models with treatment assignment as the only factor. Cumulative incidence curves, which adjust for competing risks for censoring due to all-cause mortality, were used to show the accrual of events with time in the two treatment groups (24).
The distribution of age at baseline is presented as mean and the range and categorical baseline characteristics are shown as percentages.
|
Results
|
|---|
The baseline characteristics of the patients randomized in CAPRICORN are shown in Table 1. A total of 9% of patients (89 placebo group, 81 carvedilol group) were recorded as having a prior or ongoing history of AF/atrial flutter, and 1.1% were identified as having had ventricular tachycardia (2 placebo group, 0 carvedilol group) or fibrillation (14 placebo group, 6 carvedilol group).
A total of 96 patients (5%) were treated with an antiarrhythmic drug at the time of randomization, and, in 95 of these 96, the treatment used was amiodarone (59 placebo group, 36 carvedilol group).
Supraventricular arrhythmias.
Any supraventricular arrhythmia
Among carvedilol-treated patients, 26 of 975 (2.7%) had a report of a supraventricular arrhythmia compared with 54 of 984 (5.5%) of placebo-treated patients, representing a carvedilol/placebo HR of 0.48 (95% CI 0.30 to 0.76; log-rank p = 0.0015). After excluding patients with a history of AF/atrial flutter, 19 of 894 (2.1%) of carvedilol-treated patients and 32 of 895 (3.6%) of placebo-treated patients had a report of a supraventricular arrhythmia after randomization: HR 0.59 (95% CI 0.33 to 1.03; p = 0.062).
AF/atrial flutter
The comparable rates of AF/atrial flutter in the carvedilol and placebo groups were 22 of 975 (2.3%) and 53 of 984 (5.4%), respectively, representing an HR of 0.41 (95% CI 0.25 to 0.68; p = 0.0003) (Fig. 1). After excluding patients with a history of AF/atrial flutter, 16 of 894 (1.8%) carvedilol-treated patients and 31 of 895 (3.5%) placebo patients had a report of AF/atrial flutter after randomization: HR 0.51 (95% CI 0.28 to 0.93; p = 0.025).
View larger version (8K):
[in this window]
[in a new window]
|
Figure 1 Survival free of atrial fibrillation or atrial flutter. Dotted line = placebo; solid line = carvedilol.
|
|
Ventricular arrhythmias.
Any ventricular arrhythmia
Among carvedilol-treated patients, 26 of 975 (2.7%) had a report of a ventricular arrhythmia compared with 69 of 984 (7.0%) placebo-treated patients, representing an HR of 0.37 (95% CI 0.24 to 0.58; p < 0.0001) (Fig. 2). Among carvedilol-treated patients, there were 4 episodes of ventricular fibrillation/flutter, 6 of ventricular tachycardia, and 19 of other ventricular arrhythmias (premature beats, couplets, and so on). In the placebo group, these numbers were 17, 27, and 38, respectively.
After excluding patients with a history of ventricular fibrillation/tachycardia, 25 of 969 (2.6%) carvedilol-treated patients and 66 of 968 (6.8%) placebo-treated patients had a report of a ventricular arrhythmia after randomization: HR 0.37 (95% CI 0.23 to 0.59; p < 0.0001).
"Malignant" ventricular arrhythmias
The comparable rates of ventricular tachycardia, ventricular fibrillation, or ventricular flutter were 9 of 975 (0.9%) in the carvedilol group and 38 of 984 (3.9%) in the placebo group, representing an HR of 0.24 (95% CI 0.11 to 0.49; p < 0.0001).
Combined outcomes.
Table 2 shows the combined outcomes of death or an arrhythmia. Carvedilol reduced the risk of all combined outcomes analyzed, including the outcome of death or any reported arrhythmia.
Arrhythmias and sudden death.
Table 3 shows the relationship between arrhythmias and death from any cause and those adjudicated as sudden. Patients who experienced an arrhythmia were more likely to die and to have their mode of death classified as "sudden." There was a nonsignificant trend for fewer sudden deaths in the carvedilol group, especially in patients with an arrhythmia.
|
Discussion
|
|---|
In this retrospective, but blinded, analysis of the CAPRICORN trial, carvedilol was shown to have a striking effect, not only on the incidence of ventricular arrhythmias but also on the risk of atrial arrhythmias.
The occurrence of AF after MI is associated with a worse clinical outcome, including a higher mortality (2–4,14–17). This is the case generally and also in patients with significant left ventricular systolic dysfunction after infarction. For example, the Trandolapril Cardiac Evaluation (TRACE) investigators found that AF was an independent predictor of both a higher in-hospital and long-term mortality (4). In the TRACE study, the risk of developing AF, over a mean follow-up of 2.2 years, was reduced in the ACE inhibitor group (n = 22, 2.8%) compared with the placebo group (n = 42, 5.3%) (21).
Whether beta-blockers reduce the risk of atrial arrhythmias after MI has not been tested in a double-blind prospective, randomized, placebo-controlled trial, particularly in patients already treated with an ACE inhibitor. This analysis of the CAPRICORN trial suggests that carvedilol markedly suppresses atrial arrhythmias in these patients. It is of interest to compare these findings with the recent Danish Investigations of Arrhythmia and Mortality on Dofetilide-Myocardial Infarction (DIAMOND-MI) study, which examined the effect of a new class III antiarrhythmic agent in similar patients with those enrolled in the TRACE and CAPRICORN trials (25). In the DIAMOND-MI study 58% of patients were treated with an ACE inhibitor and 36% with a beta-blocker at the time of randomization (25). The risk of developing AF or atrial flutter, over a mean follow-up of 1.25 years, in patients in sinus rhythm at baseline was 14 of 705 (2.0%) in the placebo group and 5 of 690 (0.7%) in the dofetilide group (approximately 65% risk reduction, p = 0.09) (25).
The effect of beta-blockers on ventricular arrhythmias in the post-MI setting is more clearly established. Both substudies of the large beta-blocker secondary prevention trials and independent studies showed significant reductions in all grades of ventricular arrhythmias with propranolol, timolol, and metoprolol (9–13,26–29). None of these studies, however, focused on patients with substantial left ventricular systolic dysfunction; indeed, it seems that high-risk patients were excluded from these studies (22,23). Furthermore, these studies were conducted before the benefits of ACE inhibitors, one of which is to reduce ventricular arrhythmias, had been established (19,30,31). We were able to confirm that carvedilol reduced ventricular arrhythmias, even in high-risk patients treated with an ACE inhibitor. Indeed, the magnitude of this effect, be it on all ventricular arrhythmias or just "malignant" arrhythmias, was striking; the latter were reduced by 70%. Whether the size of this effect reflects just the beta-blocking action of carvedilol or an additional antiarrhythmic action of the molecule (for example, carvedilol has been shown, in vitro, to block HERG potassium channels) cannot be determined from the current study (32,33).
That the substantial reduction in "malignant" ventricular arrhythmias did not translate into a clearly significant reduction in sudden death (placebo 69 of 984 [7%], carvedilol 51 of 975 [5%]; p = 0.098), as reported in the main CAPRICORN trial results paper (23), might, at first sight, seem surprising. However, with only 120 sudden deaths in total, we had low statistical power to detect such a treatment effect. Furthermore, any such treatment effect might have been diluted by nonarrhythmic causes of sudden death such as bradycardia/asystole, pulmonary embolism, reinfarction leading to catastrophic pump failure, stroke, and other noncoronary vascular events (e.g., aortic aneurysm rupture) the risk of which may not be reduced by beta-blockade (34). The use of amiodarone in a small proportion of patients might have similarly reduced our ability to show a difference between carvedilol and placebo. Furthermore, further analysis of mode of death in those experiencing an arrhythmia showed a strong trend to fewer sudden deaths in the carvedilol group.
The present analysis has a number of limitations. First, it was not prespecified. Second, it is based on an examination of AEs and SAEs without electrocardiographic validation of arrhythmias. Spontaneous AE and SAE reporting might be expected to underestimate the true incidence of arrhythmias. Comparison with other recent studies (e.g., the TRACE and DIAMOND studies), however, suggests that this is not the case for supraventricular arrhythmias (i.e., our rates of arrhythmias were similar to the rates reported in those other trials). We also believe that under- or overreporting of clinically important ventricular arrhythmias is unlikely. The recent Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy Survival Study (EPHESUS) is useful for comparison. Over an average follow-up of 1.33 years, 54 of 3,313 (1.6%) of placebo-treated patients (75% of whom were treated with a beta-blocker) were hospitalized for a ventricular arrhythmia. In the carvedilol group in the CAPRICORN trial, 9 of 975 (0.9%) of patients experienced a "malignant" ventricular arrhythmia over 1.3 years compared with 38 of 984 (3.9%) in the placebo group.
However, spontaneous reporting might exaggerate the apparent antiarrhythmic effect of carvedilol because this drug is likely to reduce awareness of an arrhythmia.
What are the clinical implications of these findings? We believe that they reinforce the value of beta-blockers as essential treatment in patients with acute infarction (35). Though other treatments (i.e., an implantable cardioverter defibrillator [36] and eplerenone [37]) reduce the risk of sudden death (and death from any cause) in patients already taking a beta-blocker, carvedilol also reduces the risk of reinfarction (as do other beta-blockers) and of atrial arrhythmias.
In summary, in this nonprespecified analysis, carvedilol appeared to reduce the incidence of investigator-reported (but nonadjudicated) atrial and ventricular arrhythmias in patients with acute MI and associated impairment of left ventricular systolic dysfunction. This antiarrhythmic effect is additional to that known to be exerted by ACE inhibitors in these patients.
.
|
Footnotes
|
|---|
The CAPRICORN study was funded by GlaxoSmithKline and Roche Pharmaceuticals.
|
References
|
|---|
1. Risk stratification and survival after myocardial infarction N Engl J Med 1983;309:331-336.[Abstract]
2. Behar S, Zahavi Z, Goldbourt U, Reicher-Reiss H. Long-term prognosis of patients with paroxysmal atrial fibrillation complicating acute myocardial infarctionSPRINT study group. Eur Heart J 1992;13:45-50.[Abstract/Free Full Text]
3. Maggioni AP, Zuanetti G, Franzosi MG, et al. Prevalence and prognostic significance of ventricular arrhythmias after acute myocardial infarction in the fibrinolytic eraGISSI-2 results. Circulation 1993;87:312-322.[Abstract/Free Full Text]
4. Pedersen OD, Bagger H, Kober L, Torp-Pedersen C. The occurrence and prognostic significance of atrial fibrillation/-flutter following acute myocardial infarctionTRACE study group. TRAndolapril Cardiac Evalution. Eur Heart J 1999;20:748-754.[Abstract/Free Full Text]
5. Pratt C, Lichstein E. Ventricular antiarrhythmic effects of beta-adrenergic blocking drugs: a review of mechanism and clinical studies J Clin Pharmacol 1982;22:335-347.[Abstract]
6. Morganroth J. Antiarrhythmic effects of beta-adrenergic blocking agents in benign or potentially lethal ventricular arrhythmias Am J Cardiol 1987;60:10D-14D.[Medline]
7. Podrid PJ, Fuchs T, Candinas R. Role of the sympathetic nervous system in the genesis of ventricular arrhythmia Circulation 1990;82(Suppl 2):I103-13.
8. Haverkamp W, Gulker H, Hindricks G, Breithardt G. Effects of beta-blockade on the incidence of ventricular tachyarrhythmias during acute myocardial ischaemia: experimental findings and clinical implications Basic Res Cardiol 1990;95(Suppl 1):293-303.
9. The MIAMI Trial Research Group Metoprolol in acute myocardial infarctionArrhythmias. Am J Cardiol 1985;56:35G-38G.[CrossRef][Medline]
10. Ryden L, Ariniego R, Arnman K, et al. A double-blind trial of metoprolol in acute myocardial infarctionEffects on ventricular tachyarrhythmias. N Engl J Med 1983;308:614-618.[Abstract]
11. von der Lippe G, Lund-Johansen P, Kjekshus J. Effect of timolol on late ventricular arrhythmias after acute myocardial infarction Acta Med Scan Suppl 1981;651:253-263.
12. Lichstein E, Morganroth J, Harrist R, Hubble E. Effect of propranolol on ventricular arrhythmiaThe beta-blocker heart attack trial experience. Circulation 1983;67:I5-10.
13. Morganroth J, Lichstein E, Byington R. Beta-Blocker Heart Attack trial: impact of propranolol therapy on ventricular arrhythmias Prev Med 1985;14:346-357.[CrossRef][Web of Science][Medline]
14. Goldberg RJ, Yarzebski J, Lessard D, et al. Recent trends in the incidence rates of and death rates from atrial fibrillation complicating initial acute myocardial infarction: a community-wide perspective Am Heart J 2002;143:519-527.[CrossRef][Web of Science][Medline]
15. Rathore SS, Berger AK, Weinfurt KP, et al. Acute myocardial infarction complicated by atrial fibrillation in the elderly: prevalence and outcomes Circulation 2000;101:969-974.[Abstract/Free Full Text]
16. Wong CK, White HD, Wilcox RG, et al. New atrial fibrillation after acute myocardial infarction independently predicts death: the GUSTO-III experience Am Heart J 2000;140:878-885.[CrossRef][Web of Science][Medline]
17. Pizzetti F, Turazza FM, Franzosi MG, et al. Incidence and prognostic significance of atrial fibrillation in acute myocardial infarction: the GISSI-3 data Heart 2001;86:527-532.[Abstract/Free Full Text]
18. Sogaard P, Gotzsche CO, Ravkilde J, et al. Ventricular arrhythmias in the acute and chronic phases after acute myocardial infarctionEffect of intervention with captopril. Circulation 1994;90:101-107.[Abstract/Free Full Text]
19. Kingma JH, van Gilst WH, Peels CH, et al. Acute intervention with captopril during thrombolysis in patients with first anterior myocardial infarctionResults from the Captopril and Thrombolysis Study (CATS). Eur Heart J 1994;15:898-907.[Abstract/Free Full Text]
20. Budaj A, Cybulski J, Cedro K, et al. Effects of captopril on ventricular arrhythmias in the early and late phase of suspected acute myocardial infarctionRandomized, placebo-controlled substudy of ISIS-4. Eur Heart J 1996;17:1506-1510.[Abstract/Free Full Text]
21. Pedersen OD, Bagger H, Kober L, Torp-Pedersen C. Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction Circulation 1999;100:376-380.[Abstract/Free Full Text]
22. Dargie HJ. Design and methodology of the CAPRICORN trial—a randomised double blind placebo controlled study of the impact of carvedilol on morbidity and mortality in patients with left ventricular dysfunction after myocardial infarction Eur J Heart Failure 2000;2:325-332.[Free Full Text]
23. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial Lancet 2001;357:1385-1390.[CrossRef][Web of Science][Medline]
24. Kalbfleisch JD, Prentice RL. The Statistical Analysis of Failure Time Data2nd edition. Hoboken, NJ: Wiley; 2002.
25. Pedersen OD, Bagger H, Keller N, et al. Efficacy of dofetilide in the treatment of atrial fibrillation-flutter in patients with reduced left ventricular function: a Danish investigations of arrhythmia and mortality of dofetilide (DIAMOND) substudy Circulation 2001;104:292-296.[Abstract/Free Full Text]
26. Evemy KL, Pentecost BL. Intravenous and oral practolol in the acute stages of myocardial infarction Eur J Cardiol 1978;7:391-398.[Web of Science][Medline]
27. Olsson G, Rehnqvist N, Lundman T, Melcher A. Metoprolol treatment after acute myocardial infarctionEffects on ventricular arrhythmias and exercise tests during 6 months. Acta Med Scand 1981;210:59-65.[Web of Science][Medline]
28. Friedman LM, Byington RP, Capone RJ, et al. Effect of propranolol in patients with myocardial infarction and ventricular arrhythmia J Am Coll Cardiol 1986;7:1-8.[Abstract]
29. Rehnqvist N, Olsson G, Erhardt L, Ekman AM. Metoprolol in acute myocardial infarction reduces ventricular arrhythmias both in the early stage and after the acute event Int J Cardiol 1987;15:301-308.[CrossRef][Web of Science][Medline]
30. Sogaard P, Gotzsche CO, Ravkilde J, et al. Ventricular arrhythmias in the acute and chronic phases after acute myocardial infarctionEffect of intervention with captopril. Circulation 1994;90:101-107.
31. Budaj A, Cybulski J, Cedro K, et al. Effects of captopril on ventricular arrhythmias in the early and late phase of suspected acute myocardial infarctionRandomized, placebo-controlled substudy of ISIS-4. Eur Heart J 1996;17:1506-1510.[Abstract/Free Full Text]
32. Takusagawa M, Komori S, Matsumura K, et al. The inhibitory effects of carvedilol against arrhythmias induced by coronary reperfusion in anesthetized rats J Cardiovasc Pharmacol Ther 2000;5:105-112.[Medline]
33. Karle CA, Kreye VA, Thomas D, et al. Antiarrhythmic drug carvedilol inhibits HERG potassium channels Cardiovasc Res 2001;49:361-370.[Abstract/Free Full Text]
34. First International Study of Infarct Survival Collaborative Group Mechanisms for the early mortality reduction produced by beta-blockade started early in acute myocardial infarction: ISIS-1 Lancet 1988;1:921-923.[CrossRef][Medline]
35. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction executive summary: a report of the ACC/AHA Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines on the Management of Patients with Acute Myocardial Infarction) J Am Coll Cardiol 2004;110:588-636.
36. Moss AJ, Zareba W, Hall WJ, et al. ., Multicenter Automatic Defibrillator Implantation Trial II InvestigatorsProphylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-883.[Abstract/Free Full Text]
37. Pitt B, Remme W, Zannad F, et al. ., Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study InvestigatorsEplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309-1321.[Abstract/Free Full Text]
Related Article
-
Three decades of clinical trials with beta-blockers: The contribution of the CAPRICORN trial and the effect of carvedilol on serious arrhythmias
- Craig M. Pratt
J. Am. Coll. Cardiol. 2005 45: 531-532.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
J. D. Mishkin, S. J. Saxonhouse, G. W. Woo, T. A. Burkart, W. M. Miles, J. B. Conti, R. S. Schofield, S. F. Sears, and J. M. Aranda Jr
Appropriate Evaluation and Treatment of Heart Failure Patients After Implantable Cardioverter-Defibrillator Discharge Time to Go Beyond the Initial Shock.
J. Am. Coll. Cardiol.,
November 24, 2009;
54(22):
1993 - 2000.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. C. van den Broek, I. Nyklicek, P. H. van der Voort, M. Alings, A. Meijer, and J. Denollet
Risk of ventricular arrhythmia after implantable defibrillator treatment in anxious type D patients.
J. Am. Coll. Cardiol.,
August 4, 2009;
54(6):
531 - 537.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Klapholz
{beta}-Blocker Use for the Stages of Heart Failure
Mayo Clin. Proc.,
August 1, 2009;
84(8):
718 - 729.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Schmitt, G. Duray, B. J. Gersh, and S. H. Hohnloser
Atrial fibrillation in acute myocardial infarction: a systematic review of the incidence, clinical features and prognostic implications
Eur. Heart J.,
May 1, 2009;
30(9):
1038 - 1045.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Cappato
Atrial fibrillation complicating acute myocardial infarction: how should it be interpreted and how should it be treated and prevented?
Eur. Heart J.,
May 1, 2009;
30(9):
1035 - 1037.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, K. Michl, et al.
2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation
J. Am. Coll. Cardiol.,
April 14, 2009;
53(15):
e1 - e90.
[Full Text]
[PDF]
|
|
|
|
|
|
|
2005 WRITING COMMITTEE MEMBERS, S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, et al.
2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation
Circulation,
April 14, 2009;
119(14):
e391 - e479.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. G. Cosio, E. Aliot, G. L. Botto, H. Heidbuchel, C. J. Geller, P. Kirchhof, J.-C. De Haro, R. Frank, J. P. Villacastin, J. Vijgen, et al.
Delayed rhythm control of atrial fibrillation may be a cause of failure to prevent recurrences: reasons for change to active antiarrhythmic treatment at the time of the first detected episode
Europace,
January 1, 2008;
10(1):
21 - 27.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-R. Neuberger, C. Mewis, D. J. van Veldhuisen, U. Schotten, I. C. van Gelder, M. A. Allessie, and M. Bohm
Management of atrial fibrillation in patients with heart failure
Eur. Heart J.,
November 1, 2007;
28(21):
2568 - 2577.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Schwartz and E. Vanoli
From exercise training to sudden death prevention via adrenergic receptors
Am J Physiol Heart Circ Physiol,
November 1, 2007;
293(5):
H2631 - H2633.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Kloner and D. S. Cannom
Uncertainty on the Use of Aldosterone Antagonists for Primary Therapy for Sudden Cardiac Death in the Setting of Implanted Devices
Circulation,
June 12, 2007;
115(23):
2983 - 2989.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Rivard, H. Sinno, A. Shiroshita-Takeshita, G. Schram, T.-K. Leung, and S. Nattel
The pharmacological response of ischemia-related atrial fibrillation in dogs: Evidence for substrate-specific efficacy
Cardiovasc Res,
April 1, 2007;
74(1):
104 - 113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. J. Remme, C. Torp-Pedersen, J. G.F. Cleland, P. A. Poole-Wilson, M. Metra, M. Komajda, K. Swedberg, A. Di Lenarda, P. Spark, A. Scherhag, et al.
Carvedilol Protects Better Against Vascular Events Than Metoprolol in Heart Failure: Results From COMET
J. Am. Coll. Cardiol.,
March 6, 2007;
49(9):
963 - 971.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Dobre, D. J. van Veldhuisen, M. J.L. DeJongste, C. Lucas, G. Cleuren, R. Sanderman, A. V. Ranchor, and F. M. Haaijer-Ruskamp
Prescription of beta-blockers in patients with advanced heart failure and preserved left ventricular ejection fraction. Clinical implications and survival
Eur J Heart Fail,
March 1, 2007;
9(3):
280 - 286.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. A. Nasr, A. Bouzamondo, J.-S. Hulot, O. Dubourg, J.-Y. Le Heuzey, and P. Lechat
Prevention of atrial fibrillation onset by beta-blocker treatment in heart failure: a meta-analysis
Eur. Heart J.,
February 8, 2007;
(2007)
ehl484v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Southerland, D. M. Milhorn, R. D. Foreman, B. Linderoth, M. J. L. DeJongste, J. A. Armour, V. Subramanian, M. Singh, K. Singh, and J. L. Ardell
Preemptive, but not reactive, spinal cord stimulation mitigates transient ischemia-induced myocardial infarction via cardiac adrenergic neurons
Am J Physiol Heart Circ Physiol,
January 1, 2007;
292(1):
H311 - H317.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Writing Committee Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al.
ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: full text: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society
Europace,
September 1, 2006;
8(9):
651 - 745.
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al.
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society
J. Am. Coll. Cardiol.,
August 15, 2006;
48(4):
e149 - e246.
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al.
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society
Circulation,
August 15, 2006;
114(7):
e257 - e354.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. van Veldhuisen, H. Aass, D. El Allaf, P. H.J.M. Dunselman, L. Gullestad, M. Halinen, J. Kjekshus, L. Ohlsson, H. Wedel, J. Wikstrand, et al.
Presence and development of atrial fibrillation in chronic heart failure: Experiences from the MERIT-HF Study
Eur J Heart Fail,
August 1, 2006;
8(5):
539 - 546.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. R. Hanna, B. Heeke, H. Bush, L. Brosius, D. King-Hageman, J. F. Beshai, and J. J. Langberg
The Relationship Between Stature and the Prevalence of Atrial Fibrillation in Patients With Left Ventricular Dysfunction
J. Am. Coll. Cardiol.,
April 18, 2006;
47(8):
1683 - 1688.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Molenaar, T. Christ, U. Ravens, and A. Kaumann
Carvedilol blocks {beta}2- more than {beta}1-adrenoceptors in human heart
Cardiovasc Res,
January 1, 2006;
69(1):
128 - 139.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. N. Singh
{beta}-Adrenergic Blockers as Antiarrhythmic and Antifibrillatory Compounds: An Overview
Journal of Cardiovascular Pharmacology and Therapeutics,
October 1, 2005;
10(4_suppl):
S3 - S14.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. H. Hohnloser
Ventricular Arrhythmias: Antiadrenergic Therapy for the Patient with Coronary Artery Disease
Journal of Cardiovascular Pharmacology and Therapeutics,
October 1, 2005;
10(4_suppl):
S23 - S31.
[Abstract]
[PDF]
|
|
|
|
|
|
|
G. V. Naccarelli
Antiadrenergic Therapy in the Control of Atrial Fibrillation
Journal of Cardiovascular Pharmacology and Therapeutics,
October 1, 2005;
10(4_suppl):
S33 - S43.
[Abstract]
[PDF]
|
|
|
|
|
|
|
P. R. Kowey
A Review of Carvedilol Arrhythmia Data in Clinical Trials
Journal of Cardiovascular Pharmacology and Therapeutics,
October 1, 2005;
10(4_suppl):
S59 - S68.
[Abstract]
[PDF]
|
|
|
|
|
|
|
Developed in Collaboration With the American Colle, Endorsed by the Heart Rhythm Society, S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, et al.
ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure)
J. Am. Coll. Cardiol.,
September 20, 2005;
46(6):
1116 - 1143.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, K. Michl, et al.
ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart Rhythm Society
Circulation,
September 20, 2005;
112(12):
1825 - 1852.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Lehman
Evidently...
Evid. Based Med.,
August 1, 2005;
10(4):
105 - 105.
[Full Text]
[PDF]
|
|
|
|
Top
Abstract
Methods