CARDIOLOGY/SYSTEMATIC REVIEW SNAPSHOT

TAKE-HOME MESSAGE
In patients with ST-segment elevation myocardial infarction (STEMI), when
percutaneous coronary intervention is not an option, reperfusion therapy with the
fibrinolytic agents tenecteplase, reteplase, or accelerated alteplase (90 minutes of
infusion) plus parenteral anticoagulation has better overall safety and efficacy than
other regimens.

In Patients With ST-Segment Elevation

METHODS Myocardial Infarction, Which Fibrinolytic
Agent Is the Safest and Most Effective?
DATA SOURCE EBEM Commentators
Ashis Shrestha, MD
The authors searched PubMed, Department of General Practice and Emergency Medicine
EMBASE, the Cochrane Library, Cli Patan Academy of Health Sciences
nicalTrials.gov, and the World Kathmandu, Nepal
Health Organization International Darlene R. House, MD, MS
Clinical Trials Registry Platform Department of General Practice and Emergency Medicine
from inception to February Patan Academy of Health Sciences
28, 2017. Kathmandu, Nepal
Department of Emergency Medicine
Indiana University School of Medicine
STUDY SELECTION Indianapolis, IN
Randomized controlled trials Julie L. Welch, MD
comparing fibrinolytic agents with Department of Emergency Medicine
Indiana University School of Medicine
an approved indication of
Indianapolis, IN
reperfusion therapy in adults with
STEMI, whether administered alone
or in combination with adjunctive Results
anticoagulant therapy, were Selected network meta-analysis results for efficacy and safety of fibrinolytic regimens.*
included. Studies assessing primary
All-Cause Mortality
or facilitated percutaneous Within 30 to 35 Days, Major Bleeding,
intervention versus fibrinolytics Fibrinolytic Regimen RR (95% CI) RR (95% CI)
were excluded. Primary outcomes
Acc tPAþPAC 1.0 [Reference] 1.0 [Reference]
included all-cause mortality within TNKþPAC 1.01 (0.90–1.13) 0.79 (0.63–1.00)
30 to 35 days (efficacy) and major rPAþPAC 1.04 (0.94–1.15) 0.88 (0.69–1.12)
bleeding (safety). SKþPAC 1.14 (1.05–1.24) 0.92 (0.70–1.21)
tPAþPAC 1.26 (1.10–1.45) 0.63 (0.44–0.92)

DATA EXTRACTION AND RR, Relative risk; CI, confidence interval; Acc tPA, accelerated alteplase infusion during 90 minutes (guideline
recommended); PAC, parenteral anticoagulants; TNK, tenecteplase; rPA, reteplase; SK, streptokinase; tPA,
SYNTHESIS nonaccelerated alteplase infusion during 3 hours.
*RR greater than 1.0 tends toward more deaths and bleeding.
Two authors independently
screened studies for inclusion and
extracted data, which was cross-
checked by 2 independent reviewers. Forty studies met inclusion criteria, therapy alone or in combination
Discrepancies were resolved by involving 128,071 STEMI patients with antithrombotic agents,
consensus. Study bias was assessed treated with 12 fibrinolytic regi- including parenteral anticoagulants
with the Cochrane Collaboration’s mens. Four fibrinolytic agents (ie, low-molecular-weight heparin,
risk-of-bias tool. A conventional (streptokinase, reteplase, ten- heparin, anti-Xa inhibitor, and
meta-analysis was performed by ecteplase, and alteplase at 2 sepa- direct thrombin inhibitor) or
using a random-effects model. rate dosing regimens) glycoprotein IIb or IIIa inhibitors
were compared as reperfusion (ie, abciximab, tirofiban, or

Volume -, no. - : - 2018 Annals of Emergency Medicine 1

Systematic Review Snapshot

streptokinase or nonaccelerated availability of more effective,

Heterogeneity was determined alteplase with or without safer fibrinolytic regimens.5 As
with the Cochran Q test and I2
parenteral anticoagulation. The cardiovascular deaths increase
statistic. A network meta-analysis
with consistency model compared
network meta-analysis showed globally, implementing guidelines
intervention data. Evidence that monotherapy fibrinolytics using fibrinolytic regimens that
quality was assessed with the (streptokinase and nonaccelerated maximize safety and decrease
Grading of Recommendations alteplase) had increased risk of harm is important to improving
Assessment, Development and mortality compared with global emergency care for STEMI.6
Evaluation. guideline-recommended acceler-
Editor’s Note: This is a clinical
ated alteplase with parenteral synopsis, a regular feature of the
anticoagulation. The addition of Annals’ Systematic Review Snapshots
eptifibatide) (Table). Thirty-six tri- glycoprotein IIb or IIIa inhibitors (SRS) series. The source for this
als specified that aspirin was a part to any fibrinolytic regimen signifi- systematic review snapshot is:
of therapy. Thirty-nine studies cantly increased the risk of major Jinatongthai P,
assessed all-cause mortality and 32 Kongwatcharapong J, Foo CY,
bleeding and therefore should be et al. Comparative efficacy and
reported major bleeding. In terms avoided. safety of reperfusion therapy with
of bias, 27 studies had an unclear fibrinolytic agents in patients
risk bias, with 13 having high risk of For clinicians with limited access with ST-segment elevation
bias at least 1 category of masking of to percutaneous coronary inter- myocardial infarction: a
participants or personnel (6 vention, tenecteplase or reteplase systematic review and network
studies), masking of outcome as- meta-analysis. Lancet.
with parenteral anticoagulation is 390:747-759.
sessments (1 study), selective as safe and effective as accelerated
outcome reporting (2 studies), and alteplase with parenteral anti- 1. Lambert L, Brown K, Segal E, et al.
other bias (6 studies). coagulation and offers the addi- Association between timeliness of
tional advantage of a longer half- reperfusion therapy and clinical outcomes in
Commentary life, making it easier to admin-
ST-elevation myocardial infarction. JAMA.
2010;303:2148-2155.
Timely reperfusion therapy is ister as a single intravenous bolus 2. Gershlick AH, Banning AP, Myat A, et al.
essential for successful manage- injection. Alteplase has a short Reperfusion therapy for STEMI: is there still a
role for thrombolysis in the era of primary
ment of STEMI.1 Thrombolysis half-life and requires a bolus, fol- percutaneous coronary intervention? Lancet.
plays a significant role when lowed by an infusion. The single- 2013;382:624-632.
access to percutaneous coronary bolus options may be advanta- 3. Berkowitz SD, Granger CB, Pieper KS, et al.
Incidence and predictors of bleeding after
intervention is limited or not geous when treatment must be contemporary thrombolytic therapy for
available in a timely manner, initiated before a long transport myocardial infarction. The Global Utilization
particularly in rural settings or time to a percutaneous coronary of Streptokinase and Tissue Plasminogen
intervention center. With these 3 Activator for Occluded Coronary Arteries
low- and middle-income countries (GUSTO) I Investigators. Circulation.
in which percutaneous coronary regimens available, non- 1997;95:2508-2516.
intervention is not available.2 With accelerated alteplase and strepto- 4. Huynh T, Cox JL, Massel D, et al. Predictors of
risks of bleeding, stroke, and kinase should be avoided because intracranial hemorrhage with fibrinolytic
therapy in unselected community patients: a
intracranial hemorrhage, use of of associated higher mortality report from the FASTRAK II project. Am Heart
the most effective and safest rates. However, because of cost, J. 2004;148:86-91.
fibrinolytic regimen is critical.3,4 streptokinase continues to be used 5. Mark DB, Hlatky MA, Califf RM, et al. Cost
effectiveness of thrombolytic therapy with
extensively as the primary treat- tissue plasminogen activator as compared
This systematic review found that ment for STEMI in low- with streptokinase for acute myocardial
in STEMI patients, tenecteplase, and middle-income countries. infarction. N Engl J Med.
reteplase, and accelerated alte- Although studies in the United 1995;332:1418-1424.
6. Roth GA, Forouzanfar MH, Moran AE, et al.
plase (90-minute infusion) plus States have shown alteplase to be Demographic and epidemiologic drivers of
parenteral anticoagulation were more cost-effective than strepto- global cardiovascular mortality. N Engl J
the most effective regimens (ie, kinase, further cost-effective ana- Med. 2015;372:1333-1341.
lower mortality), with an accept- lyses in low- and middle-income Michael Brown, MD, MSc, Jestin N.
able safety profile (ie, lower risk of countries may help demonstrate Carlson, MD, MS, and Alan Jones, MD,
bleeding), compared with the benefit needed to advocate serve as editors of the SRS series.

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