This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (75)  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Topic Collections  • Revascularization  • Thrombolysis  • Cardiovascular System  • Cardiovascular Disease/ Myocardial Infarction  • Cardiovascular Intervention  • Alert me on articles by topic  Social Bookmarking   What's this?

Is the Slope of the Curve the Shape of the Future?

Bernard J. Gersh, MB, ChB, FRCP; Gregg W. Stone, MD; Harvey D. White, DSc; David R. Holmes, Jr, MD

JAMA. 2005;293:979-986.

Current options for reperfusion therapy in patients admitted to a community hospital without cardiac catheterization facilities include administration of fibrinolytic drugs followed by observation, with referral to angiography driven by symptoms and signs of ischemia; transfer to a tertiary care center for primary percutaneous coronary intervention (PCI); or a strategy of facilitated PCI in which administration of fibrinolytics and platelet glycoprotein IIb/IIIa inhibitors (alone or in combination) is followed by transfer for immediate angiography and PCI if appropriate. We systematically analyzed multiple randomized and nonrandomized trials to review the pathophysiology of reperfusion therapy in acute myocardial infarction to derive insights about the likelihood of success of a strategy of facilitated PCI compared with transfer only or fibrinolysis only. The basis for the recommendations made herein is a hypothetical curve relating the duration of symptoms before reperfusion to reduction in mortality and extent of myocardial salvage. During the first 2 to 3 hours after symptom onset, a striking benefit of reperfusion is present; within this period, time to treatment is critical. Subsequently, a mortality benefit is still present but of decreasing magnitude over time. In this situation, the priority is to open the artery, and time to treatment is less critical. Results of facilitated PCI may depend largely on timing of presentation. If presentation is late after symptom onset (ie, on the "flat" part of the curve), there will be little mortality benefit from earlier patency and patients will be subject to the bleeding risks of fibrinolytic drugs. In contrast, among patients presenting very early (60-90 minutes after symptom onset), outcomes with fibrinolytic therapy alone are excellent, and it will be difficult for any other strategy to result in a significant improvement. But in patients presenting 2 to 3 hours after onset of symptoms, a strategy of facilitated PCI may move patients from the plateau to the descending limb of the curve, with a substantial improvement in myocardial salvage and mortality. Two large ongoing trials may provide definitive answers to these issues.

Author Affiliations: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn (Drs Gersh and Holmes); Department of Cardiology, Columbia University, and Cardiovascular Research Foundation, New York, NY (Dr Stone); and Coronary Care and Cardiovascular Research, Green Lane Cardiology, Auckland City Hospital, Auckland, New Zealand (Dr White).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Reperfusion Injury, Microvascular Dysfunction, and Cardioprotection: The "Dark Side" of Reperfusion
Prasad et al.
Circulation 2009;120:2105-2112.
FULL TEXT  

Benefit of Facilitated Percutaneous Coronary Intervention in High-Risk ST-Segment Elevation Myocardial Infarction Patients Presenting to Nonpercutaneous Coronary Intervention Hospitals
Herrmann et al.
J Am Coll Cardiol Intv 2009;2:917-924.
ABSTRACT | FULL TEXT  

The Ideal Reperfusion Strategy for the ST-Segment Elevation Myocardial Infarction Patient With Expected Delay to Percutaneous Coronary Intervention: Paradise Lost or Paradise Renamed?
Henry and Larson
J Am Coll Cardiol Intv 2009;2:931-933.
FULL TEXT  

Effect of Supersaturated Oxygen Delivery on Infarct Size After Percutaneous Coronary Intervention in Acute Myocardial Infarction
Stone et al.
Circ Cardiovasc Interv 2009;2:366-375.
ABSTRACT | FULL TEXT  

Efficacy and Safety of Immediate Angioplasty Versus Ischemia-Guided Management After Thrombolysis in Acute Myocardial Infarction in Areas With Very Long Transfer Distances: Results of the NORDISTEMI (NORwegian study on DIstrict treatment of ST-Elevation Myocardial Infarction)
Bohmer et al.
J Am Coll Cardiol 2009;0:j.jacc.2009.08.007v1-15073.
ABSTRACT | FULL TEXT  

Primary Percutaneous Coronary Angioplasty With and Without Eptifibatide in ST-Segment Elevation Myocardial Infarction: A Safety and Efficacy Study of Integrilin-Facilitated Versus Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction (ASSIST)
Le May et al.
Circ Cardiovasc Interv 2009;2:330-338.
ABSTRACT | FULL TEXT  

Orphan targets for reperfusion injury
Inserte et al.
Cardiovasc Res 2009;83:169-178.
ABSTRACT | FULL TEXT  

Longer-Term Follow-Up of Patients Recruited to the REACT (Rescue Angioplasty Versus Conservative Treatment or Repeat Thrombolysis) Trial.
Carver et al.
J Am Coll Cardiol 2009;54:118-126.
ABSTRACT | FULL TEXT  

Association of door-to-balloon time and mortality in patients admitted to hospital with ST elevation myocardial infarction: national cohort study
Rathore et al.
BMJ 2009;338:b1807-b1807.
ABSTRACT | FULL TEXT  

Primary PCI as the preferred reperfusion therapy in STEMI: it is a matter of time
Terkelsen et al.
Heart 2009;95:362-369.
ABSTRACT | FULL TEXT  

Long-term effectiveness of early administration of glycoprotein IIb/IIIa agents to real-world patients undergoing primary percutaneous interventions: results of a registry study in an ST-elevation myocardial infarction network
Ortolani et al.
Eur Heart J 2009;30:33-43.
ABSTRACT | FULL TEXT  

Adjunctive antithrombotic therapy during primary percutaneous coronary intervention
De Luca
Eur Heart J Suppl 2008;10:J2-J14.
ABSTRACT | FULL TEXT  

PCI after lytic therapy: when and how?
Dudek et al.
Eur Heart J Suppl 2008;10:J15-J20.
ABSTRACT | FULL TEXT  

Time Is Muscle: Translation Into Practice
Antman
J Am Coll Cardiol 2008;52:1216-1221.
ABSTRACT | FULL TEXT  

Implementation of Guidelines for the Treatment of Acute ST-Elevation Myocardial Infarction: The Cologne Infarction Model Registry
Flesch et al.
Circ Cardiovasc Interv 2008;1:95-102.
ABSTRACT | FULL TEXT  

Angioplasty Strategies in ST-Segment-Elevation Myocardial Infarction: Part I: Primary Percutaneous Coronary Intervention
Stone
Circulation 2008;118:538-551.
FULL TEXT  

Angioplasty Strategies in ST-Segment-Elevation Myocardial Infarction: Part II: Intervention After Fibrinolytic Therapy, Integrated Treatment Recommendations, and Future Directions
Stone
Circulation 2008;118:552-566.
FULL TEXT  

Commentary: The Role of Percutaneous Coronary Intervention in ST-Segment-Elevation Myocardial Infarction
Bates and Nallamothu
Circulation 2008;118:567-573.
FULL TEXT  

Facilitated PCI in Patients with ST-Elevation Myocardial Infarction
Ellis et al.
NEJM 2008;358:2205-2217.
ABSTRACT | FULL TEXT  

Does Thrombolytic Therapy Facilitate or Foil Primary PCI?
Leopold
NEJM 2008;358:2277-2279.
FULL TEXT  

Factors Associated With Longer Time From Symptom Onset to Hospital Presentation for Patients With ST-Elevation Myocardial Infarction
Ting et al.
Arch Intern Med 2008;168:959-968.
ABSTRACT | FULL TEXT  

Metabolic Management of Acute Myocardial Infarction Comes to the Fore and Extends Beyond Control of Hyperglycemia
Opie
Circulation 2008;117:2172-2177.
FULL TEXT  

Adverse outcomes in fibrinolytic-based facilitated percutaneous coronary intervention: insights from the ASSENT-4 PCI electrocardiographic substudy
McDonald et al.
Eur Heart J 2008;29:871-879.
ABSTRACT | FULL TEXT  

Intracoronary KAI-9803 as an Adjunct to Primary Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial Infarction
Direct Inhibition of {delta}-Protein Kinase C Enzy
Circulation 2008;117:886-896.
ABSTRACT | FULL TEXT  

Systems of Care to Improve Timeliness of Reperfusion Therapy for ST-Segment Elevation Myocardial Infarction During Off Hours The Mayo Clinic STEMI Protocol.
Holmes et al.
J Am Coll Cardiol Intv 2008;1:88-96.
ABSTRACT | FULL TEXT  

Relationship of treatment delays and mortality in patients undergoing fibrinolysis and primary percutaneous coronary intervention. The Global Registry of Acute Coronary Events
Nallamothu et al.
Heart 2007;93:1552-1555.
ABSTRACT | FULL TEXT  

Development of Systems of Care for ST-Elevation Myocardial Infarction Patients: Gaps, Barriers, and Implications
Nallamothu et al.
Circulation 2007;116:e68-e72.
FULL TEXT  

Facilitated percutaneous coronary intervention: current concepts, promises, and pitfalls
Kiernan et al.
Eur Heart J 2007;28:1545-1553.
ABSTRACT | FULL TEXT  

Primary angioplasty vs. early routine post-fibrinolysis angioplasty for acute myocardial infarction with ST-segment elevation: the GRACIA-2 non-inferiority, randomized, controlled trial
Fernandez-Aviles et al.
Eur Heart J 2007;28:949-960.
ABSTRACT | FULL TEXT  

Effect of Door-to-Balloon Time on Patient Mortality
Brodie et al.
J Am Coll Cardiol 2006;48:2600-2600.
FULL TEXT  

Narrative review: reperfusion strategies for ST-segment elevation myocardial infarction.
Ting et al.
ANN INTERN MED 2006;145:610-617.
ABSTRACT | FULL TEXT  

Percutaneous Coronary Intervention After Fibrinolysis: A Multiple Meta-Analyses Approach According to the Type of Strategy
Collet et al.
J Am Coll Cardiol 2006;48:1326-1335.
ABSTRACT | FULL TEXT  

Facilitated Percutaneous Coronary Intervention
Borden and Faxon
J Am Coll Cardiol 2006;48:1120-1128.
ABSTRACT | FULL TEXT  

WEST: new data on the integration of early thrombolysis and mechanical intervention in the early management of STEMI
Steg and Danchin
Eur Heart J 2006;27:1511-1512.
FULL TEXT  

Implementation of Guidelines Improves the Standard of Care: The Viennese Registry on Reperfusion Strategies in ST-Elevation Myocardial Infarction (Vienna STEMI Registry)
Kalla et al.
Circulation 2006;113:2398-2405.
ABSTRACT | FULL TEXT  

Evaluating and improving the quality of care for acute myocardial infarction: can regionalization help?
Hannan
JAMA 2006;295:2177-2179.
FULL TEXT  

Postconditioning: Reduction of reperfusion-induced injury
Zhao and Vinten-Johansen
Cardiovasc Res 2006;70:200-211.
ABSTRACT | FULL TEXT  

Aborted myocardial infarction: a new target for reperfusion therapy
Verheugt et al.
Eur Heart J 2006;27:901-904.
ABSTRACT | FULL TEXT  

Selection of the optimal reperfusion strategy for STEMI: does time matter?
Gersh and Antman
Eur Heart J 2006;27:761-763.
FULL TEXT  

Implementation of reperfusion therapy in acute myocardial infarction. A policy statement from the European Society of Cardiology
Bassand et al.
Eur Heart J 2005;26:2733-2741.
ABSTRACT | FULL TEXT  

The Case for Community Hospital Angioplasty
Wharton et al.
Circulation 2005;112:3509-3534.
FULL TEXT  

Effect of Clopidogrel Pretreatment Before Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction Treated With Fibrinolytics: The PCI-CLARITY Study
Sabatine et al.
JAMA 2005;294:1224-1232.
ABSTRACT | FULL TEXT  

Limitations of the study evaluating fibrinolytic therapy and in-hospital PCI for ST-elevation myocardial infarction
Osman et al.
Eur Heart J 2005;26:1684-1684.
FULL TEXT  

Acute PCI for ST-Segment Elevation Myocardial Infarction: Is Later Better Than Never?
Gibbons and Grines
JAMA 2005;293:2930-2932.
FULL TEXT