Failed Thrombolysis

Abstract & Commentary

By Michael H. Crawford, MD, Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.
This article originally appeared in the August issue of
Clinical Cardiology Alert. It was peer review by Rakesh Mishra, MD.

Synopsis: Rescue PCI in the setting of early fibrinolytic failure improves mortality, but this is tempered by a possible increase in the risk of thromboembolic stroke.

Source: Patel TN, et al. A Meta-Analysis of Randomized Trials of Rescue Percutaneous Coronary Intervention After Failed Fibrinolysis. Am J Cardiol. 2006;97:1685-1690.

Rescue percutaneous coronary intervention (RPCI) has been advocated for failed thrombolysis in acute STEMI when available, but there is a lack of agreement on the efficacy of this approach. Thus, Patel and colleagues reviewed the English language literature from 1985 to 2004 to find randomized, controlled trials on this topic, and then performed a meta-analysis to evaluate whether RPCI improved outcomes. The primary outcome was short-term mortality (up to 30 days). Secondary outcomes were stroke and heart failure. Five trials were included in the analysis: RESCUE I and II, MERLIN, and REACT. A total of 942 were enrolled in these trials; 405 got RPCI, 395 conservative therapy, and 142 repeat thrombolysis in REACT. The latter patients were excluded. There was no difference in baseline characteristics in the groups. All patients received aspirin; heparin use was variable; stent use varied from 29 to 50%; and glycoprotein IIb/IIIa inhibitor use varied from 3%-55%.

Results: Mortality was reduced 36% (RR 0.64, CI 0.4-1.00, P = 0.048) in the RPCI Groups. The number needed to treat (NNT) with RPCI to prevent one death was 25. There were only 11 confirmed thromboembolic strokes; 9 in the RPCI groups, which resulted in a nonsignificant increased risk with RPCI (RR 3.61, CI 0.91-14.27, P = 0.07). Heart Failure decreased marginally with RPCI (RR 0.72, CI 0.51-1.01, P = 0.06). Patel et al concluded that rescue PCI for failed thrombolytic therapy improves mortality, but may increase thromboembolic stroke.

Commentary

Since almost all hospitals with PCI capabilities perform primary PCI for acute STEMI, the issue is whether non-PCI hospitals, which use thrombolysis, should transfer patients with failed thrombolysis to centers where rescue PCI can be done. Prior randomized, controlled trials on this issue have been either very small (28 to 151 patients) angiographic studies (RESCUE) or small clinical studies (MERLIN, REACT, under 300 patients each). Despite the marked differences in trial design, all but RESCUE II (29 patients) showed a trend toward reduced 30-day mortality in the RPCS group, and this was statistically significant on the meta-analysis with a NNT of 25. This is encouraging since the time from chest pain onset-to-arrival in the catheterization laboratory was > 4 hours for all 5 trials. For example, in the MERLIN trial the pain-to-lysis time averaged 180 minutes; the lysis-to-lab time was 146 minutes; and the pain-to-lab time was 326 minutes (almost 5.5 hours).

The major concern has been the complication of thromboembolic stroke, which was most notable in MERLIN. Of the 11 such strokes, 7 were in MERLIN; 6 in the RPCI arm and 1 in the conservative arm. There were none to very few in the other trials, and this risk was nonsignificant in the meta-analysis. Of the 6 strokes in the RPCI arm of MERLIN, 3 were periprocedure and 2 resulted in long-term disability. This excess of strokes in MERLIN may be because streptokinase was used almost exclusively in this trial. Also, in MERLIN only, 66% of those randomized to RPCI actually got it. In addition, there was a low rate of stent and GP IIb/IIIa use in MERLIN. Thus, many believe MERLIN is an outlier in this regard and are not concerned about stroke risk. There were no differences in major bleeding in these trials (intracranial, GI), but minor groin bleeding was increased by RPCI as expected.

At this point, rescue PCI should be considered the ideal treatment for failed thrombolysis in acute STEMI unless contraindicated or not feasible. These studies do not provide much information about the timing of RPCI, but it would seem that if RPCI can be accomplished in < 6 hours from pain onset, it should be strongly considered. If this sort of timing is feasible, it raises the issue of whether routine transfer for primary PCI is a better approach. In my experience, unless there is a well-developed special relationship between hospitals to accomplish such transfers on a routine basis in a timely manner, it is better to do thrombolysis first. Organizing an occasional RPCI requires less coordination and effort overall, but experiences at other centers may dictate a different approach. Despite the simplicity of the time = muscle concept in acute STEMI, selecting the approach that provides the most reperfusion in the least time for all patients remains a challenge.

References

1. Burge S, Wedzicha JA. COPD Exacerbations: Definitions and Classifications. Eur Respir J Suppl. 2003;41:46s-53s.

2. National Collaborating Centre for Chronic Conditions. Chronic Obstructive Pulmonary Disease. National Clinical Guideline on Management of Chronic Obstructive Pulmonary Disease in Adults in Primary and Secondary Care. Thorax. 2004;59:1-232. http://thorax.bmjjournals.com/content/vol59/suppl_1/

3. Global Initiative for Chronic Obstructive Lung Disease (GOLD). www.goldcopd.com

4. Sullivan SD, et al. The Economic Burden of COPD. Chest. 2000;117(2 Suppl):5S-9S.

5. Wedzicha JA. Exacerbations: Etiology and Pathophysiologic Mechanisms. Chest. 2002;121:136S-141S.

6. Wedzicha JA, Donaldson GC. Exacerbations of Chronic Obstructive Pulmonary Disease. Respir Care. 2003;48:1204-1213.

7. Sapey E, Stockley RA. COPD Exacerbations. 2: Aetiology. Thorax. 2006;61:250-258.

8. Seemungal TA, et al. Effect of Exacerbation on Quality of Life in Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 1998;157(5 Pt 1):1418-1422.

9. Seemungal TA, et al. Time Course and Recovery of Exacerbations in Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2000;161:1608-1613.

10. Donaldson GC, et al. Relationship Between Exacerbation Frequency and Lung Function Decline in Chronic Obstructive Pulmonary Disease. Thorax. 2000;57:847-852.

11. Wilkinson TM, et al. Early Therapy Improves Outcomes of Exacerbations of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2004;169:1298-1303.

12. Wedzicha JA. Role of Viruses in Exacerbations of Chronic Obstructive Pulmonary Disease. Proc Am Thorac Soc. 2004;1:115-120.

13. Cameron RJ, et al. Virus Infection in Exacerbations of Chronic Obstructive Pulmonary Disease Requiring Ventilation. Intensive Care Med. 2006;32:1022-1029.

14. Hurst JR, Wedzicha JA. Chronic Obstructive Pulmonary Disease: The Clinical Management of an Acute Exacerbation. Postgrad Med J. 2004;80:497-505.

15. Anthonisen NR. Bacteria and Exacerbations of Chronic Obstructive Pulmonary Disease. N Engl J Med. 2002;347:526-527.

16. Sethi S, et al. New Strains of Bacteria and Exacerbations of Chronic Obstructive Pulmonary Disease. N Engl J Med. 2002;347:465-471.

17. Tillie-Leblond I, et al. Pulmonary Embolism in Patients with Unexplained Exacerbation of Chronic Obstructive Pulmonary Disease: Prevalence and Risk Factors. Ann Intern Med. 2006;144:390-396.

18. American Thoracic Society/European Respiratory Society Task Force. Standards for the Diagnosis and Management of Patients with COPD. www-test.thoracic.org/copd/.

19. Anthonisen NR, et al. Antibiotic Therapy in Exacerbations of Chronic Obstructive Pulmonary Disease. Ann Intern Med. 1987;106:196-204.

20. Pierson DJ. Clinical Practice Guidelines for Chronic Obstructive Pulmonary Disease: A Review and Comparison of Current Resources. Respir Care. 2006;51:277-288.

21. Leff B, et al. Hospital at Home: Feasibility and Outcomes of a Program to Provide Hospital-Level Care at Home for Acutely Ill Older Patients. Ann Intern Med. 2005;143:798-808.

22. Ram FS, et al. Hospital at Home for Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Cochrane Database Syst Rev. 2003;(4):CD003573.