Is an additional post-myocardial infarction ß-blocker trial required in the era of early revascularization?

Hans Mickleya,*, Hans Eiskjærb and Hans Erik Bøtkerc

a Odense University Hospital, Odense, Denmark
b Aarhus University Hospital, Skejby, Denmark
c Aarhus University Hospital, Skejby, Denmark

* Corresponding author: Hans Mickley, MD, Ph.D., Department of Cardiology, Odense University Hospital, 5000 Odense C, Denmark. Tel.: +4565411894
E-mail address: hans.mickley{at}dadlnet.dk

Received 17 February 2003; revised 9 April 2003; accepted 20 June 2003

The new guidelines addressing the management of patients with acute coronary syndromes have recently been published.1,2These guidelines are the first in Europe after the redefinition of acute myocardial infarction (AMI). Treatment strategies in the early phase of AMI have changed dramatically during the last 10–15 years. However, the evidence that confirms a prognostic benefit of ß-blockade in AMI was obtained in the 1980s. Only one randomized, post-AMI trial addresses the effects of ß-blockade in the era of ACE-inhibitors, statins, anti-platelet therapy, fibrinolytic treatment or early coronary revascularization.3This study, however, excluded patients with a LVEF >40%.

Do we really have data that justify recommendation of ß-blockers to all patients with acute coronary syndromes in the absence of contraindications as proposed in the guidelines?1,2The new definition of AMI and the changes in treatment strategies may imply that it is more appropriate to conclude that the prognostic effects of ß-blockade after AMI are not fully known in all subgroups of patients.

What are the immediate consequences of the new definition of AMI? Many patients with unstable angina will now be labelled as having had an AMI due to the high sensitivity of new biochemical markers. The prognosis of AMI may be more favourable with the new compared to the old definition, because CK-MB negative and troponin positive patients have a better outcome than patients who are both CK-MB positive and troponin positive. In addition, the redefinition increases the incidence of AMI. These circumstances may affect the efficacy of ß-blockers in AMI because ß-blockade has not been shown to reduce mortality or risk of AMI in patients with unstable angina according to the old definitions.

What do we know about the effects of ß-blocker treatment in post-AMI patients with a normal or slightly reduced LV function? Data from up to date randomized trials are not available. Thus, in the CAPRICORN study only patients with an EF ≤40% were included.3However, retrospective data from more than 200 000 patients with AMI during 1994–1995 indicate that ß-blockers reduce 2-year mortality 7.7% in patients with an EF ≥50%. Because of their lower mortality rates the absolute benefit is considerably less than in patients with reduced EF. Furthermore, subgroup analyses of thrombolysed patients have not clearly shown any effects of ß-blockers on long-term mortality. Therefore, controlled randomized trials in survivors of AMI with normal or close to normal LV function are warranted.

The increasing use of primary PCI in ST-elevation AMI and early coronary angiography in non-ST-elevation AMI yield immediate and important information about anatomy and pathology of the coronary arteries. Is there any need for ß-blocker therapy in patients who are completely revascularized and who have no evidence of residual ischaemia? If so, for which duration? The exact mechanism underlying the ß-blocker induced reduction in mortality after AMI is not fully understood. Possible mechanisms for the prevention of sudden death by ß-blockade may be the reduction of excess sympathetic activity or the increase in vagal tone. If these mechanisms are predominant, the indication for ß-blocker therapy following AMI may be independent of revascularization.

In conclusion, the evidence for indefinite use of ß-blockers to all patients following AMI does not appear to be valid in the new millennium. We believe that a new post-AMI ß-blocker trial in the era of early revascularization is justified.

References

  1. Bertrand ME, Simoons ML, Fox KAA et al. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. The Task Force on the Management of Acute Coronary Syndromes of The European Society of Cardiology. Eur Heart J. 2002;23:1809–1840.[Free Full Text]
  2. Van De Werf F, Adrission D, Betriu A et al. Management of acute myocardial infarction in patients presenting with ST-segment elevation. The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J. 2003;24:28–66.[Free Full Text]
  3. The CAPRICORN Investigators. Effect of carvedilol on outcom after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 2001;357:1385–1390.[CrossRef][Medline]




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