Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Review: Evidence supporting reduced death and reinfarction by percutaneous coronary intervention after thrombolysis is inconclusive

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ACP J Club. 2006 May-Jun;144:61. doi:10.7326/ACPJC-2006-144-3-061

Related Content in this Issue
• Companion Abstract and Commentary: Rescue angioplasty reduced cardiovascular and cerebrovascular outcomes in acute MI after failed thrombolytic therapy


Clinical Impact Ratings

Emergency Med: 7 stars

Hospitalists: 4 stars

Cardiology: 4 stars


Source Citation

Cantor WJ, Brunet F, Ziegler CP, Kiss A, Morrison LJ. Immediate angioplasty after thrombolysis: a systematic review. CMAJ. 2005;173:1473-81. [PubMed ID: 16330637]


Abstract

Question

In patients with ST-segment elevation myocardial infarction (STEMI) in a prehospital setting or a community hospital emergency department, is immediate or early percutaneous coronary intervention (PCI) after thrombolysis more effective than delayed PCI?

Methods

Data sources: MEDLINE, EMBASE/Excerpta Medica, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, American Heart Association (AHA) EndNote 7 Master Library, and relevant references (from 1985 to 2004).

Study selection and assessment: Exclusion criteria were PCI done > 24 hours after thrombolysis, no PCI intervention, sample size < 30, or no control group. Assessment of individual study quality was based on 7 levels of evidence (level 1 = highest) and 4 degrees (excellent, fair, poor, and unsatisfactory) of design and methods according to the AHA International Liaison Committee on Resuscitation classification.

Outcomes: Death and a composite endpoint of death and reinfarction at 12 months.

Main results

37 studies met the selection criteria; 18 were randomized controlled trials (RCTs). Meta-analysis (8 RCTs with good or fair degree, n = 2598) showed that PCI and delayed PCI groups did not differ for death or the composite endpoint of death and reinfarction within 12 months (1 RCT at 6 mo) (Table). Among these 8 RCTs, meta-analysis of 3 stent-era RCTs (n = 861) showed that the PCI group had lower mortality and lower rates of the composite endpoint (1 study at 6 mo) (Table).

Conclusions

In patients with ST-segment elevation myocardial infarction in a prehospital setting or a community hospital emergency department, evidence from meta-analysis of 8 trials does not show a reduction in death and reinfarction with immediate or early (< 24 h) percutaneous coronary intervention. Stent-era trials show a reduction.

Source of funding: No external funding.

For correspondence: Dr. W.J. Cantor, Southlake Regional Health Centre, Newmarket, Ontario, Canada.


Table. Immediate or early percutaneous coronary intervention (PCI) vs delayed PCI after thrombolysis for ST-segment elevation myocardial infarction at 12 months (1 study at 6 mo)*

Outcomes Number of trials (n) RRR (95% CI) NNT (CI)
Composite endpoint† 8 (2598) 16% (−1.1 to 31) Not significant
3 (stent era) (861) 36% (9.1 to 56) 15 (10 to 57)
5 (prestent era) (1737) 6.0% (−277 to 25) Not significant
Mortality 8 (2598) 9.8% (−17 to 31) Not significant
3 (stent era) (861) 43% (7.2 to 65) 24 (16 to 140)
RRI (CI) NNH
5 (prestent era) (1737) 9.0% (−20 to 48) Not significant

*Abbreviations defined in Glossary; RRR, RRI, NNT, NNH, and CI calculated from odds ratios and control event rates provided by author using a fixed-effects model.
†Death and reinfarction.


Commentary

Treatment of STEMI with PCI is well-established. However, because of limited facilities for PCI, first-line therapy in 30% to 70% of patients is thrombolytic therapy (1). Although thrombolysis reduces mortality more than placebo, normal blood flow (TIMI grade 3 flow) is restored in only 60% of patients (2). Given the intermediate success rate of thrombolytics in reperfusing the infarct-related artery as well as the high rate of reocclusion/reinfarction, the strategy of routine early invasive evaluation with revascularization after thrombolysis has been hypothesized to further improve outcomes.

The REACT trial shows the superiority of rescue PCI over conservative treatment or repeated thrombolysis in patients without clinical reperfusion at 90 minutes after initial thrombolysis. It is important to note that patients who were transferred to a tertiary care center for an interventional procedure also benefited.

In the meta-analysis by Cantor and colleagues, 3 stent-era RCTs showed that the early invasive strategy reduced mortality and recurrent MI more than the conservative strategy after thrombolysis for STEMI. In contrast, meta-analysis of 5 balloon angioplasty-era RCTs did not show benefit of an early invasive strategy. This result reflects some of the improvements in modern PCI, such as smaller guide catheters, low-profile stents, thienopyridines, glycoprotein IIb/IIIa inhibitors, and other adjunctive therapies (and perhaps more experienced operators). These technologies have greatly reduced the early hazard associated with rescue PCI as well as substantially improved the short- and long-term patency of infarct vessels. Mechanistically, an open infarct-related artery and “open myocardium,” both early and late, led to myocardial salvage in STEMI; improved infarct healing; and reduced rates of reinfarction, angina, lethal arrhythmias, and heart failure.

The results of REACT, the review by Cantor and colleagues, and other studies have several practical implications for clinical practice in patients with STEMI who receive thrombolytics. First, these patients should be transferred immediately to a PCI center. A caveat exists from the PRAGUE trial (3) that supports transfer for PCI without administering thrombolytics if PCI will be available in less than 90 minutes. Second, except for patients with severe comorbid conditions, early angiography should be done during the index hospitalization.

How early is early for the postthrombolysis patient? In REACT, the review by Cantor and colleagues, and other current studies (3-5), angiography or PCI was done within 4 to 24 hours from symptom onset and from 1.5 to 24 hours after thrombolysis. A limitation of these studies is that they do not specifically address the relative benefit that patients may achieve as a function of clinical evidence of successful versus failed thrombolysis. Hence, whether a patient with strong clinical evidence of reperfusion (resolution of symptoms and electrocadiographic changes) would reap the same benefit from an emergency catheterization as a patient without clinical evidence of reperfusion after thrombolysis needs further investigation.

The results of REACT and Cantor and colleagues' study are consistent with most other recent studies comparing an early, invasive strategy with a conservative one across the spectrum of acute coronary syndromes: Routine, early invasive evaluation improved outcome.

Alfonso Suarez, MD
Sanjay Rajdev, MD
William B. Hillegass, MD, MPH
University of Alabama at Birmingham
Birmingham, Alabama, USA


References

1. Eagle KA, Goodman SG, Avezum A, et al. Practice variation and missed opportunities for reperfusion in ST-segment-elevation myocardial infarction: findings from the Global Registry of Acute Coronary Events (GRACE). Lancet. 2002;359:373-7. [PubMed ID: 11844506]

2. Cannon CP, Gibson CM, McCabe CH, et al. TNK-tissue plasminogen activator compared with front-loaded alteplase in acute myocardial infarction: results of the TIMI 10B trial. Thrombolysis in Myocardial Infarction (TIMI) 10B Investigators. Circulation. 1998;98:2805-14. [PubMed ID: 9860780]

3. Widimský P, Groch L, Zelízko M, et al. Multicentre randomized trial comparing transport to primary angioplasty vs immediate thrombolysis vs combined strategy for patients with acute myocardial infarction presenting to a community hospital without a catheterization laboratory. The PRAGUE study. Eur Heart J. 2000;21:823-31. [PubMed ID: 10781354]

4. Fernandez-Avilés F, Alonso JJ, Castro-Beiras A, et al. Routine invasive strategy within 24 hours of thrombolysis versus ischaemia-guided conservative approach for acute myocardial infarction with ST-segment elevation (GRACIA-1): a randomised controlled trial. Lancet. 2004;364:1045-53. [PubMed ID: 15380963]

5. Scheller B, Hennen B, Hammer B, et al. Beneficial effects of immediate stenting after thrombolysis in acute myocardial infarction. J Am Coll Cardiol. 2003;42:634-41. [PubMed ID: 12932593]