Rescue Angioplasty or Repeat Fibrinolysis After Failed Fibrinolytic Therapy for ST-Segment Myocardial Infarction: A Meta-Analysis of Randomized Trials Rescue Angioplasty or Repeat Fibrinolysis After Failed Fibrinolytic Therapy for ST-Segment Myocardial Infarction: A Meta-Analysis of Randomized Trials Harindra C. Wijeysundera, MD; Ram Vijayaraghavan, MD; Brahmajee K. Nallamothu, MD, MPH; JoAnne M. Foody, MD; Harlan M. Krumholz, MD, SM; Christopher O. Phillips, MD, MPH; Amir Kashani, MD, MS; John J. You, MD; Jack V. Tu, MD, PhD; Dennis T. Ko, MD, MSc Published in the Journal of the American College of Cardiology January 30, 2007

Clinical Trial Results . org

Rescue Angioplasty or Repeat Fibrinolysis After Failed Fibrinolytic Therapy for STEMI: Background

• The investigators sought to best estimate the benefits and risks associated with rescue PCI and repeat fibrinolytic therapy as compared with conservative management in patients with failed fibrinolytic therapy for ST segment myocardial infarction (STEMI).

Wijeysundera HC, et al. JACC. 30 Jan 2007:49(4): 422-30.

Clinical Trial Results . org

Rescue Angioplasty or Repeat Fibrinolysis After Failed Fibrinolytic Therapy for STEMI: Background (cont.)

• Fibrinolytic therapy is the most common treatment for STEMI; however, the best strategy to treat patients who fail to acheive reperfusion after fibrinolytic therapy remains uncertain.

Wijeysundera HC, et al. JACC. 30 Jan 2007:49(4): 422-30.

Clinical Trial Results . org

Rescue Angioplasty or Repeat Fibrinolysis After Failed Fibrinolytic Therapy for STEMI: Study Design 1177 patients from 8 clinical trials with follow-up duration ranging from hospital discharge to 6 months

Meta-Analysis of randomized trials using fixed-effects model.

There were 6 trials that randomized 908 patients to rescue PCI or conservative therapy and 3 trials that randomized 410 patients to repeat fibrinolysis or conservative therapy (REACT trial used for both analyses).

PCI n=454 Treatment n=454

Follow-up ranged from hospital discharge to 6 months

Repeat Fibrinolysis n=206 Conservative Treatment n=204

Follow-up ranged from hospital discharge to 6 months   Clinical efficacy outcomes: All-cause mortality, heart failure, and reinfarction Safety outcomes: Stroke, major bleeding, and minor bleeding

Wijeysundera HC, et al. JACC. 30 Jan 2007:49(4): 422-30.

Clinical Trial Results . org

Rescue PCI vs Conservative Treatment: Outcomes

20 15 10 5 Rescue PCI vs Conservative Treatment p = 0.09

12.7

10.4

7.3

p = 0.05

17.8

p = 0.04

10.7

6.1

p = 0.04

3.4

0.7

p < 0.001

16.6

3.6

•

The overall absolute reduction in the composite endpoint of all-cause mortality, heart failure, or reinfarction was substantial in the rescue-PCI group, requiring only 9 patients to be treated to yield 1 patient with benefit.

0 Mortality CHF Rescue PCI ReMI Stroke Minor Bleed Conservative treatment

Wijeysundera HC, et al. JACC. 30 Jan 2007:49(4): 422-30.

Clinical Trial Results . org

Repeat Fibrinolysis vs Conservative Treatment: Outcomes

Repeat Fibrinolysis vs Conservative Treatment 20 15 10 5 p = 0.14

15.7

10.7

p = 0.09

11.8

6.5

p = 0.42

p = 0.03

14.6

7.8

•

On the contrary, repeat fibrinolysis was not associated with significant improvements in all cause mortality or reinfarction, and it also showed an increased risk for minor bleeding.

4.3

2.7

0 Mortality ReMI Repeat fibrinolysis Major Bleed Minor Bleed Conservative treatment

Wijeysundera HC, et al. JACC. 30 Jan 2007:49(4): 422-30.

Clinical Trial Results . org

Rescue Angioplasty or Repeat Fibrinolysis After Failed Fibrinolytic Therapy for STEMI: Limitations

• Despite the absence of statistically significant heterogeneity, there are substantial differences in the entrance criteria of the included trials.

• It is difficult to evaluate reperfusion without performing angiography, and this is a major barrier to the adoption of a standardized rescue policy for management of failed fibrinolytic therapy.

Wijeysundera HC, et al. JACC. 30 Jan 2007:49(4): 422-30.

Clinical Trial Results . org

Rescue Angioplasty or Repeat Fibrinolysis After Failed Fibrinolytic Therapy for STEMI: Limitations (cont.)

• The meta analysis’ pooled estimates are based on <500 patients randomized per arm reflecting the difficulty in recruiting patients for trials in this area.

• Given the small numbers in these analyses, the ability to detect a reduction in mortality may have been underpowered (particularly in the repeat lytic arm), and likewise spuriously false positive results may emerge.

Wijeysundera HC, et al. JACC. 30 Jan 2007:49(4): 422-30.

Clinical Trial Results . org

Rescue Angioplasty or Repeat Fibrinolysis After Failed Fibrinolytic Therapy for STEMI: Summary

• This meta-analysis, which systematically reviewed the existing literature of randomized trials on treatment strategies for STEMI patients who fail fibrinolytic therapy, found that rescue PCI was associated with significant risk reductions for heart failure and reinfarction.

• In addition, the overall absolute reduction in the composite end point of all-cause mortality, heart failure, or reinfarction was statistically significant for rescue PCI.

Wijeysundera HC, et al. JACC. 30 Jan 2007:49(4): 422-30.

Clinical Trial Results . org

Rescue Angioplasty or Repeat Fibrinolysis After Failed Fibrinolytic Therapy for STEMI: Summary (cont.)

• Rescue PCI was associated with an increased risk of stroke and minor bleeding and thus, the potential benefits of rescue PCI must be interpreted in the context of its risks.

• Few conclusions can be reached regarding repeat fibrinolysis given the small sample sizes, although more bleeding was observed with this approach.

Wijeysundera HC, et al. JACC. 30 Jan 2007:49(4): 422-30.

Clinical Trial Results . org