European Heart Journal Advance Access originally published online on November 4, 2005
European Heart Journal 2006 27(1):118-119; doi:10.1093/eurheartj/ehi642
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Is the level of evidence for the use of beta-blockers in acute myocardial infarction satisfactory enough?
Institute for Cardiovascular Diseases
Emergency Hospital
Coronary Unit A
Clinical Centre of Serbia
Pasterova 2
Makenzijeva 85/8
11000 Belgrade
Serbia and Montenegro
Tel: +381 11 3441117
Fax: +381 11 3619068
E-mail address: igormr{at}beocity.net
The cornerstone of each therapy's recommendation should be the impact on survival. In the August 2004 issue of the European Heart Journal, expert consensus opinion on beta-blockers stated that during the acute phase of myocardial infarction, oral beta-blockers are indicated in all patients without contraindications (Class I, level of evidence A).1 The consensus group opinion was supported by the data from the pre-reperfusion ISIS-12 and MIAMI3 trials and post-reperfusion TIMI-II trial4 which compared two time protocols of metoprolol administration and, therefore, was not controlled with a non-beta-blocker or another beta-blocker. It is understandable that the results from pre-reperfusion studies cannot be simply incorporated into a modern concept of AMI treatment.
Retrospective analysis from PCI studies (PAMI-2, Stent PAMI, Air PAMI, PAMI noSOS, and CADILLAC) was used to support the premise of mortality reduction with pre-PCI intravenous and post-PCI peroral use of beta-blockers.5,6 However, none of these studies were designed to randomly assess the effects of beta-blockers on mortality.
Oral beta-blockers are further recommended for long-term use and for survival improvement in all patients who recover from AMI and do not present contraindications (Class I, level of evidence A); this recommendation is based on the data from a meta-analysis of 31 randomized trials, Hjalmarson's trial, Cooperative Cardiovascular Project, BHAT and Norwegian trial.7,8 However, all these trials are from the pre-reperfusion era or use registry as a database. None of these trials included random assessment of beta-blockers in the post-reperfusion modern algorithm, including PCI, fibrinolysis, ACE-inhibitors, aspirin, and statines. Furthermore, the document states that the benefit of beta-blockers in low-risk patients is questionable.
CAPRICORN, the only randomized post-reperfusion trial in AMI patients with ventricular dysfunction, showed all-cause mortality reduction with carvedilol when compared with placebo.9 However, CAPRICORN did not reach the pre-specified higher level of statistical significance for the original primary endpoint of all-cause mortality (the primary endpoint was changed for co-primary during the study). Therefore, the statistical power of CAPRICORN is only borderline in favour of mortality reduction with carvedilol in high-risk AMI patients (P=0.031).
Intravenous beta-blocker administration for primary prevention of sudden death was marked as a Class I, level of evidence B. The document admitted that post hoc analysis of GUSTO-1 trial does not support intravenous use of beta-blockers in the reperfusion era.10 In TIMI-IIB trial, early intravenous metoprolol administration had no advantage over the peroral treatment.4
Evidence for the use of beta-blockers in the early stage of AMI thus results from studies in the pre-reperfusion era, registries, meta-analyses, and post hoc analysis, not designed for beta-blockers' random assessment in regard to mortality reduction after AMI.
In the absence of powerful statistical evidence for mortality reduction in the reperfusion time, we believe the impact of beta-blockers on survival after AMI has not been proved sufficiently. For a better evaluation of the role of beta-blockers in patients with AMI, randomized large trials assessing the impact on survival are obviously missing.
References
- Task Force Members, Lopez-Sendon J, Swedberg K, McMurray J, Tamargo J, Maggioni AP, Dargie H, Tendera M, Waagstein F, Kjekshus J, Lechat P, Pedersen CT. Expert consensus document on beta-adrenergic receptor blockers. The Task Force on Beta-Blockers of the European Society of Cardiology. Eur Heart J 2004;25:1341–1362.
[Free Full Text] - ISIS-I (First International Study of Infarct Survival) Collaborative Group. Randomized trial of intravenous atenolol among 16027 cases of suspected acute myocardial infarction: ISIS-I. Lancet 1986;328:57–66.[CrossRef]
- The MIAMI Trial Research Group. Metoprolol in acute myocardial infarction (MIAMI): a randomized placebo controlled international trial. Eur Heart J 1985;6:199–226.
[Abstract/Free Full Text] - Roberts R, Rogers WJ, Mueller HS, Lambrew CT, Diver DJ, Smith HC, Willerson JT, Knatterud GL, Forman S, Passamani E. Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) II-B study. Circulation 1991;83:422–437.
[Abstract/Free Full Text] - Halkin A, Grines CL, Cox DA, Garcia E, Mehran R, Tcheng JE, Griffin JJ, Guagliumi G, Brodie B, Turco M, Rutherford BD, Aymong E, Lansky AJ, Stone GW. Impact of intravenous beta-blockade before primary angioplasty on survival in patients undergoing mechanical reperfusion therapy for acute myocardial infarction. J Am Coll Cardiol 2004;43:1780–1787.
[Abstract/Free Full Text] - Kernis SJ, Harjai KJ, Stone GW, Grines LL, Boura JA, O'Neill WW, Grines CL. Does beta-blocker therapy improve clinical outcomes of acute myocardial infarction after successful primary angioplasty? J Am Coll Cardiol 2004;43:1773–1779.
[Abstract/Free Full Text] - Freemantle N, Cleland J, Young P, Mason J, Harrison J. Beta-blockade after myocardial infarction: systematic review and meta regression analysis. BMJ 1999;318:1730–1737.
[Abstract/Free Full Text] - Krumholz HM, Radford MJ, Wang Y, Chen J, Heiat A, Marciniak T. National use and effectiveness of beta-blockers for the treatment of elderly patients with acute myocardial infarction: National Cooperative Cardiovascular Project. JAMA 1998;280:623–629.
[Abstract/Free Full Text] - The CAPRICORN Investigators. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomized trial. Lancet 2001;357:1385–1390.[CrossRef][Web of Science][Medline]
- The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329:673–682.
[Abstract/Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Dietz, R. Dechend, C.-M. Yu, M. Bheda, J. Ford, M. F. Prescott, and D. L. Keefe Effects of the direct renin inhibitor aliskiren and atenolol alone or in combination in patients with hypertension1 Journal of Renin-Angiotensin-Aldosterone System, September 1, 2008; 9(3): 163 - 175. [Abstract] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||