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Therapeutics

Rescue angioplasty reduced cardiovascular and cerebrovascular outcomes in acute MI after failed thrombolytic therapy

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ACP J Club. 2006 May-Jun;144:60. doi:10.7326/ACPJC-2006-144-3-060

Related Content in this Issue
• Companion Abstract and Commentary: Review: Evidence supporting reduced death and reinfarction by percutaneous coronary intervention after thrombolysis is inconclusive


Clinical Impact Ratings

Hospitalists: 6 stars

Cardiology: 6 stars


Source Citation

Gershlick AH, Stephens-Lloyd A, Hughes S, et al. Rescue angioplasty after failed thrombolytic therapy for acute myocardial infarction. N Engl J Med. 2005;353:2758-68. [PubMed ID: 16382062]


Abstract

Question

In patients with acute myocardial infarction (MI) after failed thrombolytic therapy, does rescue percutaneous coronary intervention (PCI) reduce cardiovascular and cerebrovascular events?

Methods

Design: Randomized controlled trial (Rescue Angioplasty versus Conservative Treatment or Repeat Thrombolysis [REACT]).

Allocation: {Unconcealed}†.*

Blinding: Blinded (outcome assessors {and data analysis}†).*

Follow-up period: 6 months.

Setting: 35 centers in the United Kingdom.

Patients: 427 patients 21 to 85 years of age (mean age 61 y, 79% men) who had MI with ST-segment elevation ≥ 0.1 mV in ≥ 2 contiguous leads (excluding V1) and had received aspirin and thrombolysis within 6 hours of symptom onset, and electrocardiogram showed failed thrombolytic therapy at 90 minutes. Exclusion criteria included probable inability to gain femoral access for intervention, left bundle-branch block, < 6 months life expectancy, hemoglobin level > 1.5 g/dL below normal range and platelet count below normal range within the previous 6 hours, elevated blood pressure, cardiogenic shock, and administration of low-molecular-weight heparin in the previous 12 hours.

Intervention: Rescue PCI (n = 144) (coronary angiography, proceeding to angiography if required, and stenting or glycoprotein IIb/IIIa receptor inhibition at discretion of the interventionist), repeated thrombolysis (alteplase or reteplase) (n = 142), or conservative therapy (n = 141).

Outcomes: Composite endpoint of death, recurrent MI, cerebrovascular event, and severe heart failure. Secondary outcomes were components of the primary outcome, bleeding, and revascularization.

Patient follow-up: 93% (intention-to-treat analysis).

Main results

At 6 months, fewer patients in the rescue PCI group had the primary composite endpoint than patients in the repeated thrombolysis group or in the conservative therapy group (Table). Rescue PCI also led to lower rates of mortality, recurrent MI, and revascularization (Table). Rescue-PCI, repeated-thrombolysis, and conservative-therapy groups did not differ for cerebrovascular events, severe heart failure, and major bleeding events, but the rescue PCI group had a higher rate of minor bleeding events than the other 2 groups (23% vs 7.0% vs 5.7%, P < 0.001).

Conclusion

In patients with acute myocardial infarction (MI) after failed thrombolytic therapy, rescue angioplasty reduced a composite endpoint of death, recurrent MI, cerebrovascular event, and severe heart failure.

*See Glossary.

†Information provided by author.

Sources of funding: British Heart Foundation and Roche Pharmaceuticals.

For correspondence: Dr. A.H. Gershlick, University Hospitals of Leicester, Leicester, England, UK. E-mail agershlick@aol.com.


Table. Rescue percutaneous coronary intervention (PCI) vs repeated thrombolysis (RT) or conservative therapy (CT) for acute myocardial infarction (MI) after failed thrombolytic therapy at 6 months‡

Outcomes Comparisons Event rates RRR (CI) NNT (CI)
Primary composite endpoint§ PCI vs RT 15% (22/144) vs 31% (44/142) 52% (24 to 70) 7 (5 to 14)
PCI vs CT 15% (22/144) vs 30% (42/141) 49% (18 to 68) 7 (5 to 19)
Mortality PCI vs (RT + CT) 6.3% vs 13% 50% (1 to 76) 16 (11 to 825)
Recurrent MI PCI vs RT 2.1% vs 11% 76% (37 to 91) 12 (11 to 25)
PCI vs CT 2.1% vs 8.5% 66% (6.7 to 88) 18 (14 to 176)
Revascularization PCI vs RT 13% vs 23% 47% (11 to 68) 10 (7 to 41)
PCI vs CT 13% vs 21% 39% (−3.5 to 64) Not significant

‡Abbreviations defined in Glossary; RRR, NNT, and CI calculated from adjusted or unadjusted hazard ratios in article.
§Death (PCI vs RT vs CT = 6.3% vs 13% vs 13%), recurrent MI (2.1% vs 11% vs 8.5%), cerebrovascular event (2.1% vs 0.7% vs 0.7%), or severe heart failure (4.9% vs 7.8% vs 7.0%).


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 considered for immediate transfer to a PCI center such that there is no delay in undergoing angiography if thrombolytic reperfusion is incomplete. 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, angiography should be done during the index hospitalization.

The optimal timing of angiography in the postthrombolysis patient remains controversial. 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]