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ST-elevation myocardial infarction – should choice of reperfusion therapy depend on the duration of symptoms?

An article from the e-journal of the ESC Council for Cardiology Practice

The prognosis of patients with acute ST-elevation infarction (STEMI) is highly dependent on rapid restoration of blood flow in the infarct-related coronary artery and in the microcirculation. Fibrinolytic therapy and primary PCI are both validated therapies. A meta-analysis of randomised trials has shown that primary PCI is superior to in-hospital fibrinolysis in patients with a duration of symptoms of less than 12 hours (1,2). This is also the case when patients are transferred to a tertiary center for primary PCI, provided the transfer time is under 90-120 minutes (1,2,3,4,5).

Acute Coronary Syndromes (ACS)


However, the ‘time is muscle’ dogma is still valid. Therefore, pre-hospital fibrinolytic therapy is a tempting option, if the diagnosis can be made and the administration of a bolus dose of the fibrinolytic can be given outside the hospital. This therapy has been shown, in a meta-analysis, to be superior to in-hospital fibrinolysis (6). Data from registers and controlled trials show that fibrinolytics are excellent therapy, when administered within the first two hours of symptoms in patients with ST-elevation MI (7). The effect of thrombolysis is less effective as time passes, whereas primary PCI also seems to be very effective after 4 hours and appears to be less time-dependent than thrombolytic therapy (7).

In the CAPTIM trial, 840 patients with acute ST-elevation - MI < 6 hours-  were randomised in the ambulance to prehospital thrombolysis with alteplase or to primary PCI (8). All patients were admitted to a hospital with acute PCI facilities. The primary endpoint was the combination of death/re-infarction/non-fatal disabling stroke at 30 days. Patients, randomised to prehospital thrombolysis with no signs of reperfusion, were treated with rescue PCI at the time of admission (26%). The primary endpoint occurred in 8.2% in the pre-hospital thrombolysis group and in 6.2% in the primary PCI group (NS). Post-hoc analysis of the data, looking at the subgroup of patients randomised within 2 hours after the onset of symptoms (n=460) revealed a strong trend towards a lower 30-day mortality in the prehospital-fibrinolysis group (2.2%) compared to the primary PCI group (5.7%) (p=0.058) (9).
In the PRAGUE-2 trial (3) there was no difference between streptokinase and transferral for primary PCI in patients with less than 3 hours of symptoms. On the other hand, in the DANAMI trial (8) the superiority of transferral for primary PCI was also observed in patients who had presented themselves shortly after the onset of symptoms. In the DANAMI-2 trial 58% of the patients were randomised within 2 hours of the onset of symptoms and 82% within 4 hours, thus providing evidence that transferral for primary PCI is also a good option in patients presenting early (4). Additional trials comparing primary PCI to prehospital thrombolysis - especially in patients presenting early- are needed.
How should we treat patients presenting themselves late (after symptoms that have lasted for more than 12 hours)? The use of thrombolysis does not provide benefit compared to conventional medical therapy in these cases. There are now data on the effect of primary PCI in these patients, but this option is currently tested in the BRAVE-2 and the OAT trial.

Conclusion:

If primary PCI can be performed within 90 to 120 minutes after diagnosis this is our preferred option in patients with STEMI of less than 12 hours. In-hospital fibrinolytic therapy is an alternative to primary PCI if primary PCI cannot be performed. In patients presenting very early (less than 2 to 3 hours) fibrinolytic therapy -preferentially administered in a pre-hospital setting- might be an alternative to primary PCI. However, at the moment, it is unclear whether patients presenting themselves in the hospital after 12 hours of symptoms may or may not benefit from primary PCI.

References


1. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003; 361: 13-20.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12517460
2. Dalby M, Bouzamando A, Lechat P, et al. Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction. Circulation 2003; 108: 1809 – 1814.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14530206
3. Widimsky P, Budesinsky T, Vorac D, et al. Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction. Eur Heart J. 2003; 24: 94-104.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12559941
4. Andersen HR, Nielsen TT, Rasmussen K, et al. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. New Engl J Med 2003; 349: 733-42.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12930925
5. Kristensen SD, Andersen HR, Thuesen L et al. Should patients with acute ST elevation myocardial infarction be transferred for primary PCI? Heart 2004: 90; 1358-136
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15486148
6. Morrison LJ, Verbeek PR, McDonald AC, et al. Mortality and prehospital thrombolysis for acute myocardial infarction. JAMA. 2000; 283: 2686-2692.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10819952
7. Boersma E, Mercado N, Poldermans D, et al. Acute myocardial infarction. Lancet 2003; 361: 847-58 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12642064
8. Bonnefoy E, Lapostolle F, Leizorovicz A, et al. Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study. Lancet 2002; 360: 825-29.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed
9. Steg PG, Bonnefoy E, Chabaud S, et al. Impact of time to treatment on mortality after prehospital fibrinolysis or primary angioplasty. Circulation. 2003; 108: 2851-2856.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14623806

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.