Percutaneous coronary intervention following intravenous fibrinolytic therapy: should it be a must?

Nicolas Danchin*

Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France

* Corresponding author. Tel: +33 156 09 37 14; fax: +33 156 09 25 72. E-mail address: nicolas.danchin{at}egp.ap-hop-paris.fr

This editorial refers to ‘Percutaneous coronary intervention and 1 year survival in patients treated with fibrinolytic therapy for acute ST-elevation myocardial infarction’{dagger} by A.J.J. McClelland et al., on page 544

Of the two methods of reperfusion therapy for acute myocardial infarction, primary percutaneous coronary intervention (PCI) is more difficult to implement but offers the best results when performed in an optimal setting.1 Although intravenous fibrinolytic therapy is easier to use, it has a lesser capacity to open the culprit artery and therefore is less likely to ensure adequate reperfusion of the jeopardized myocardium; in addition, even in the case where the artery can be reopened, the result achieved with fibrinolysis appears less ‘stable’ than that achieved with primary PCI and exposes the patient to a risk of re-infarction.1 Combining fibrinolysis with early PCI might offer a unique opportunity to associate the practicability of an easily available intravenous treatment with the capacity of PCI to either reopen persistently occluded arteries or maintain an optimal patency of arteries already reopened by the fibrinolytic treatment. Additionally, late PCI (i.e. beyond the very acute period) may limit the left ventricular remodelling process2 and therefore provide additional long-term benefits. In this context, the article by McClelland et al.3 in this issue of the Journal conveys an important message: patients treated with fibrinolytic therapy appear to be better off when they subsequently undergo PCI. This conclusion is drawn from the retrospective analysis of a consecutive series of 474 patients admitted to a single coronary care unit from 1998 to 2001 for ST elevation myocardial infarction treated with fibrinolytic therapy. Among them, 154 underwent in-hospital PCI. One-year mortality was 21% in the non-PCI group vs. 7% in the PCI group. Although patients receiving PCI had baseline characteristics that differed markedly from those without PCI, in-hospital PCI remained an independent predictor of 1-year mortality on multivariate analysis. These results, exciting as they may seem, should be interpreted with caution: analysis of registry populations is a difficult exercise as it is subject to important limitations and methodological bias, and the results presented here are a good example of the difficulty to interpret such data. In the present case, patients were included in the PCI group when they had undergone PCI at any time during their initial hospital stay and their outcomes were then compared with those of the patients who had not undergone PCI. Such a comparison automatically places the non-PCI group at a huge disadvantage: for example, a patient who underwent PCI on day 5 following admission would be included in the PCI group; however, that would mean that this patient had obviously escaped early death during the first five days. In other words, patients in the PCI group were survivors at least until the time PCI was performed; in contrast, the non-PCI group included all patients from the time fibrinolytic treatment was given, including those dying very early after thrombolysis, in some cases before PCI could even be envisaged. To avoid this bias, a solution would be to include only patients who survived until the day of the latest PCI performed in the PCI group; this solution would not be perfectly adequate either, because it would then put PCI at a disadvantage by neglecting its potential impact to improve survival before this date (i.e. patients in the non-PCI group who had died before that day might have been saved if PCI had been performed earlier). In an attempt to limit these biases, we performed a similar analysis in the French nationwide registry USIC 2000,4,5 but restricting the analysis to PCI performed on the first day following fibrinolytic treatment. The USIC 2000 registry included consecutive patients presenting to intensive care units with acute myocardial infarction in November 2000, and we analysed the impact of early PCI in the 545 patients treated with intravenous thrombolysis; 1-year survival was 95% in the 133 patients with fibrinolytic treatment followed by early PCI compared with 90% in those with fibrinolysis without early PCI (P<0.05); the difference in survival, however, became smaller (97 vs. 94%) and was no longer statistically significant when only day 2 survivors were included in the analysis (Figure 1). The true impact of early PCI is therefore likely to be less than that suggested by the first analysis, but higher than that suggested by the second one.



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Figure 1 One-year survival (Kaplan–Meier estimate) in patients treated with fibrinolysis in the French USIC 2000 registry, according to the use of early PCI within 1 day of admission. The light grey bars represent the survival rates in the whole population and the dark grey bars the survival rates in patients who did not die on the first day.

 
Because definite conclusions cannot be drawn only from the analysis of registry data, other methods must be sought to try and improve the chances to be right in recommending routine PCI following intravenous fibrinolysis.

One of the possibilities is to look at the data from randomized trials comparing primary PCI and thrombolysis according to the use of PCI after thrombolysis. Two recent trials bring information in this respect. In the Danish Multicenter Randomized Study on fibrinolytic Therapy versus Acute Coronary Angioplasty in Acute Myocardial Infarction (DANAMI-2) trial,6 the composite endpoint of mortality, re-infarction, and stroke was significantly higher in fibrinolytics-treated patients (relative risk: 1.71), compared with those undergoing primary PCI, and mortality was 8.5 vs. 6.5%. Rescue PCI after fibrinolysis, however, was performed in <2% and only 16% had PCI during the month following randomization. Conversely, in the Comparison of Angioplasty and Prehospital Thrombolysis in Acute Myocardial Infarction (CAPTIM) trial,7 30-day mortality was actually lower (3.8 vs. 4.8%, P-value was not significant) in the fibrinolysis group; in contrast with the DANAMI-2 trial, 26% of the patients had undergone rescue angioplasty after fibrinolysis and 70.4% had undergone PCI during the first 30 days. Though there were obvious differences in protocol designs between the two trials, such a large difference in the use of PCI following fibrinolysis might well account for the discrepancy between the results observed.

However, the ideal method still is to perform randomized controlled trials, with target populations as likely as possible to represent ‘real-world’ populations. The ongoing Assessment of the Safety and Efficacy of a New Treatment Strategy (ASSENT-4) trial will compare the results of primary PCI with those of fibrinolysis followed by systematic early PCI, but they will not directly address the question of what should be the appropriate management of patients treated with fibrinolytic therapy. In the late 1980s, three randomized trials,810 the European Cooperative Study, the Thrombolysis in Myocardial Infarction (TIMI) IIa, and the Should We Intervene Following Thrombolysis (SWIFT) trials assessed the effects of PCI after intravenous thrombolysis. All three failed to document a superiority of either immediate (European Cooperative Study, TIMI IIa) or early (within 48 h) (TIMI IIa and SWIFT) coronary angioplasty compared with a conservative strategy. Interestingly, the European Cooperative Study showed that angioplasty was fraught with a very high rate of immediate or early reocclusion, leading to repeat ischaemia and re-infarction. Indeed, all three trials were carried out at a time when neither coronary stents nor glycoprotein IIb/IIIa receptor blockers were available. Since then, much progress has been accomplished in the way PCIs are performed in the setting of acute myocardial infarction and the results of the initial trials can no longer be extrapolated to the current management of acute myocardial infarction, where new technical and therapeutic standards are applied. Very recently, however, the results of the British Rescue Angioplasty versus Conservative Therapy or Repeat Thrombolysis (REACT) trial were presented orally at the scientific sessions of the American Heart Association (New Orleans, USA, November 2004). This trial specifically addressed the question of the efficacy of rescue PCI in patients with persistent ST segment elevation 90 min after the initiation of fibrinolytic therapy. Though the population included in the trial was limited in size, the results show a highly significant 50% reduction in mortality and cardiovascular events in patients undergoing rescue PCI compared with those treated conservatively or receiving additional fibrinolytic treatment.

On the whole, with the REACT trial results, the question of the usefulness of rescue PCI in patients with failed fibrinolysis can be considered resolved. We still need, however, definite proof that early PCI is also beneficial in patients with ST segment elevation resolution after fibrinolysis, and the results from McClelland et al. do not bring a final answer to this further question. Until then, it remains too early to formally recommend a policy of systematic PCI after fibrinolytic treatment, though more and more evidence points to the efficacy of such a strategy.

Footnotes

{dagger} doi:10.1093/eurheartj/ehi149 Back

References

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Related articles in EHJ:

Percutaneous coronary intervention and 1 year survival in patients treated with fibrinolytic therapy for acute ST-elevation myocardial infarction
Anthony J.J. McClelland, Colum G. Owens, Simon J. Walsh, David McCarty, Thomas Mathew, Mike Stevenson, Helen Gracey, Mazhar M. Khan, and A.A. Jennifer Adgey
EHJ 2005 26: 544-548. [Abstract] [Full Text]