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Vascular Health and Risk Management 2009:5 249–256 249
REVIEW
Review of tenecteplase (TNKase) in the treatment
of acute myocardial infarction
Giovanni Melandri
Fabio Vagnarelli
Daniela Calabrese
Franco Semprini
Samuele Nanni
Angelo Branzi
Dipartimento Cardiovascolare,
Università di Bologna, Italy
Correspondence: Giovanni Melandri,
Istituto di Cardiologia, Policlinico
Sant’Orsola, Via Massarenti 9, 40138
Bologna, Italy
Tel +39 051 6364528
Fax +39 051 344859
Email giovanni.melandri@aosp.bo.it
Abstract: TNKase is a genetically engineered variant of the alteplase molecule. Three different
mutations result in an increase of the plasma half-life, of the resistance to plasminogen-activator
inhibitor 1 and of the thrombolytic potency against platelet-rich thrombi. Among available
agents in clinical practice, TNKase is the most fi brin-specifi c molecule and can be delivered as
a single bolus intravenous injection. Several large-scale clinical trials have enrolled more than
27,000 patients with acute myocardial infarction, making the use of this drug truly evidence-
based. TNKase is equivalent to front-loaded alteplase in terms of mortality and is the only
bolus thrombolytic drug for which this equivalence has been formally demonstrated. TNKase
appears more potent than alteplase when symptoms duration lasts more than 4 hours. Also,
TNKase signifi cantly reduces the rate of major bleeds and the need for blood transfusions. The
effi cacy of TNKase may be further improved by enoxaparin substitution for unfractionated
heparin, provided that enoxaparin dose adjustment is made for patients more than 75 years old.
Hitherto, the small available randomized studies and international clinical registries suggest
that pre-hospital TNKase is as effective as primary angioplasty, thus laying the foundations for
a new fi brinolytic, TNKase-based strategy as the backbone of reperfusion in acute myocardial
infarction.
Keywords: tenecteplase, TNKase, myocardial infarction, alteplase
Thrombolytic therapy versus primary angioplasty
Acute myocardial infarction presenting with ST-segment elevation (STEMI) is usually
precipitated by plaque disruption with coronary thrombosis. The quick recanalization
by either thrombolysis (TBL) or primary angioplasty (P-PCI) is the most important way
to improve the short- and long-term prognosis. Current American and European guide-
lines “prefer” P-PCI, usually believed to achieve better coronary recanalization rates,
prevent re-infarction and, ultimately, improve survival.1 However, many conceptual
and practical items dispute this presumed superiority of P-PCI (Table 1).
The claim that P-PCI leads to a mortality reduction has never been shown in any
single trial and is only suggested by an overview of 23 small trials, with only 2 trials
enrolling more than 1000 patients.2 Furthermore, this small advantage is no longer
signifi cant when the comparison is made with the accelerated infusion of alteplase.3
Too many times have we observed the failure of such positive small meta-analyses,
such as those evaluating the effects of nitrates or magnesium in acute myocardial
infarction, or the effi cacy of angiotensin-II blockers to prevent atrial fi brillation, or
the effi cacy of aspirin to prevent eclampsia.
The frequently quoted mortality reduction observed in patients treated with P-PCI
in registries is largely biased both by the incapacity of statistical methods, such as
the propensity score, to take into account important, intangible confounders, and by
the entry in the P-PCI cohort of only those patients actually being treated and not those
patients intended to treat.4
Vascular Health and Risk Management 2009:5
250
Melandri et al
Currently, only 25% of American hospitals provide
primary angioplasty and the majority of patients must be
transferred to receive the mechanical intervention.5 As a
consequence, only approximately 4% of transferred patients
receive P-PCI within 90 minutes from fi rst medical contact.6
Attempts to improve this situation so far have required
“huge” efforts, with a negligible mortality yield.7 An increase
in the number of catheterization laboratories has been pro-
posed to cope with these shortcomings. However, such a
proliferation dilutes the number of patients treated in each
catheteriztion laboratory, endangering quality,8 not to say the
costs of increasing population-based coronary angiograms
in patients without myocardial infarction. Further diffi cul-
ties arise during weekends and at night,5 again jeopardizing
quality.
Pre-hospital thrombolytic therapy
On the other hand, TBL can be delivered everywhere and
particularly when used in the pre-hospital setting is extremely
competitive with P-PCI, as demonstrated by the CAPTIM
study.9 In the recent, important MINAP registry the pre-
hospital use of TBL (nearly always TNKase) ranked among
the strongest independent predictors of in-hospital survival
in the United Kingdom.10
The American College of Cardiology/American Heart
Association guidelines encourage the recording of the
12-lead electrocardiogram “on-scene” and performing
pre-hospital TBL within 30 minutes.1 Indeed, the STEMI
picture is dominated by time, with the small incremental
benefi t of P-PCI rapidly vanishing after 90 minutes after
fi rst medical contact, particularly among young patients with
large myocardial infarction, for whom the equivalence of
TBL and P-PCI may already be achieved by a delay of only
45 minutes.11 Since time is so important, it is believed that
most benefi t may be achieved by treating as many patients
as possible in the fi rst 3 hours from the onset of symptoms,
regardless of whether TBL or P-PCI is used.12 It is now
estimated that an effi cient network can offer pre-hospital
TBL in the fi rst 3 hours in approximately 50% to 60% of
STEMI patients.13
TBL can be further improved by reducing the re-infarction
rate by adjunctive use of clopidogrel14 and enoxaparin15 as
soon as possible, ideally pre-hospital.
Pharmacologic properties
of TNKase in acute myocardial
infarction
TNKase consists of the alteplase molecule (with the excep-
tion of three point mutations) and has a molecular weight of
65,000 kD. Thr103 substitution by Asn and the mutation of the
sequence Lys296 – His-Arg-Arg to Ala-Ala-Ala-Ala prolong
the half-life and increase the resistance to plasminogen
activator inhibitor-1 (PAI-1). Additional substitution of
Asn117 by Gln results in an 8-fold decrease in clearance and
in a 200-fold increase in resistance to PAI-1.
Compared with other molecules used in clinical prac-
tice, TNKase has the highest degree of fi brin specifi city
and binding. Fibrin specifi city, in turn, implies a reduced
propensity for causing major non-cerebral bleeds, because
lytic activity is restricted to plasmin on the fi brin surface,
thus avoiding the breakdown of fi brinogen, factor V, factor
VIII and α2-antiplasmin.16 The TNKase conformational
change reduces its elimination and prolongs its plasma half-
life (α-half-life 11–20 minutes, β-half-life 41–138 minutes).
Nitrates do not appear to affect TNKase levels, as opposed to
what happens with alteplase levels.17 Moreover, the inhibition
by PAI-1 is reduced 80 times compared with alteplase.
The above properties are interesting in the treatment of
patients with STEMI, allowing single bolus infusion and pre-
venting drug inactivation at the site of platelet-rich coronary
thrombosis. In addition, TNKase has more intense anti-
platelet properties both in vitro and in vivo compared with
those of alteplase.18 In experimental models the thrombolytic
potency of TNKase is 3-fold higher than that of alteplase.19
Clinical use of TNKase in acute
myocardial infarction
The fi rst experience of dose-testing TNKase in STEMI
began in the TIMI-10A trial, showing a dose-dependent
increase in TIMI-3 fl ow rates in the 5 to 50 mg dose range
(p = 0.032).20
In the dose-escalating pilot TIMI 10B patency trial,
involving 886 patients 18 to 80 years old, bolus TNKase
injection achieved coronary TIMI grade-3 fl ow rates of 55%,
63% and 66% at 90 minutes after 30, 40 and 50 mg bolus
Table 1 Reasons for preferring thrombolysis (TBL) to primary
angioplasty (P-PCI)
TBL is immediately available everywhere
The time-delay to perform P-PCI exceeds 90 minutes in a large fraction
of patients
P-PCI does not reduce mortality consistently, particularly vs pre-
hospital TBL
TBL can be improved by new adjunctive treatments (clopidogrel and
enoxaparin)
Vascular Health and Risk Management 2009:5 251
TNKase in acute myocardial infarction
injection.21 The TIMI-3 fl ow rate was similar to that observed
in the control group, receiving front-loaded alteplase.
The safety of TNKase in STEMI was investigated in
ASSENT-1;22 3235 patients received either 30 or 40 or
50 mg TNKase as a bolus injection. The total stroke rate at
30 days was 1.5% and the intracranial hemorrhage (ICH) rate
was 0.8%, without signifi cant differences between groups.
Serious bleeding, requiring blood transfusion, occurred in
1.4% of patients in the TNKase group and in 7% of those
treated with front-loaded alteplase. Importantly, TIMI-10B
and ASSENT-1 showed the importance of reducing the
heparin dose in conjunction with TNKase, to minimize the
risk of ICH.23
Survival data with TNKase have been tested in compari-
son with those achieved using front-loaded alteplase in the
large, multicenter, confi rmation ASSENT-2 trial. A total
of 16,949 patients with STEMI in the fi rst 6 hours from the
onset of symptoms received either weight-adjusted TNKase
over 5 to 10 seconds (less than 60 kg: 30 mg; 60–69.9 kg:
35 mg; 70–79.9 kg: 40 mg; 80–89.9 kg: 45 mg; and more
than 90 kg: 50 mg) or front-loaded alteplase, along with
aspirin and reduced-dose unfractionated heparin.24 This was
an equivalence trial and all-cause mortality at 30 days was
the primary end-point. There was no difference between
TNKase and alteplase in mortality (6.18% vs 6.15%) and
stroke rate, including ICH (0.93% vs 0.94%, respectively).
Moreover, in the TNKase group there was a decreased rate
in non-cerebral bleeds (26.43% vs 28.95%, p = 0.0003),
in major bleeds (4.68% vs 5.94%, p = 0.0002) and in the
need for blood transfusion (4.25% vs 5.49%, p = 0.0002)
(Table 2). There was also a tendency for ICH to be
decreased by TNKase among the high-risk population of
females of more than 75 years old who weighed ⬍67 kg
(1.14% vs 3.02%).25 The general ASSENT-2 trial results
were confi rmed in all major subgroups, including those
related to age, gender, infarct location, Killip class and
diabetes status. Interestingly, mortality was signifi cantly
lower in the TNKase group when treatment was given more
than 4 hours after the onset of symptoms (7.0% vs 9.2%,
p = 0.018), a fi nding that could be attributed to the drug’s
fibrin specificity leading to better dissolution of older
coronary clots and confi rms from a clinical standpoint the
improved pharmacologic profi le of this molecule.
Among other in-hospital outcomes, TNKase also reduced
the rate of congestive heart failure (ie, Killip class ⬎1: 6.1%
vs 7.0%, p = 0.025).
Thus, the ASSENT-2 trial indicates that single-bolus
TNKase is equivalent to the more complex accelerated
alteplase infusion, in terms of mortality and mortality/stroke
combination, with the further advantage of a decrease in
major bleeding rate. These positive results were persisting
after 1 year.26
TNKase and the adjunctive use
of antithrombotic therapy
and of mechanical intervention
The possibility of further improving the effects of TNKase
by means of new adjunctive treatments has been explored in
ASSENT-3 and ENTIRE-TIMI 23 studies.27,28 In ASSENT-3 a
total of 6095 patients with STEMI in the fi rst 6 hours from the
onset of symptoms were treated with either full-dose TNKase
plus unfractionated heparin (UFH), full-dose TNKase plus
enoxaparin (ENOX), or half-dose TNKase plus UFH and
the GPIIB-IIIA inhibitor abciximab (ABX). Compared
with UFH, the primary end-point (30-day mortality plus
Table 2 Clinical studies with TNKase in STEMI
Trial (year) Patients Comparison Main fi ndings
ASSENT-2 (1999) 16,949 TNKase vs rt-PA TNKase and rt-PA equivalent, ↓ major bleeding with TNKase
ASSENT-3 (2001) 6,095 ENOX vs ABX vs UFHaENOX and ABX better than UFH
ENTIRE-TIMI 23 (2002) 483 ENOX vs ABX vs UFHaENOX and ABX better than UFH, ↑ bleeding with ABX
ASSENT-3-PLUS (2003) 1,639 ENOX vs UFHa, pre-hospital delivery ↓ reinfarction with ENOX, ↑ stroke/intracranial bleed
CAPITAL-AMI (2005) 170 F-PCIc vs TNKasea↓ residual ischemia with F-PCI
ASSENT-4 (2006) 1,667 F-PCIc vs P-PCIb↑ death/ischemia/bleeding in the F-PCI group
WEST (2006) 304 TNKase vs F-PCIc vs P-PCI TNKase and F-PCI comparable to P-PCI
GRACIA-2 (2007) 212 TNKased vs P-PCI ↑ reperfusion with TNKased Similar ventricular damage
aAll patients in the trial received TNKase.
bP-PCI: Primary angioplasty.
cF-PCI: Primary angioplasty, facilitated by TNKase.
dTNKase followed by routine angioplasty within 3–12 hours (“pharmaco-invasive” approach).
Vascular Health and Risk Management 2009:5
252
Melandri et al
in-hospital reinfarction and in-hospital refractory ischemia)
was reduced by ENOX (11.4% vs 15.4%, p = 0.0002) and
by the combination of UFH plus ABX (11.1%, p = 0.0001).
When in-hospital ICH or major bleeds were added to the
primary end-point (so called effi cacy plus safety end-point),
again, a signifi cant reduction was observed both in the ENOX
group (13.7% vs 17.0%, p = 0.0037) and in the UFH plus
ABX group (14.2%, p = 0.01416). ABX increased the rate
of thrombocytopenia compared to both ENOX and UFH
(3.2% vs 1.2% and 1.3% respectively, p = 0.0001) and it
also increased the cost of treatment.29
Similar results were observed in the smaller ENTIRE-
TIMI 23 trial.28 This trial had a design very similar to that
of ASSENT-3, although there was a further group receiving
ENOX in combination with ABX and half-dose TNKase.
Overall, the adjunctive use of ENOX with TNKase, com-
pared with UFH, reduced the combined incidence of death/
myocardial infarction at 30 days (4.4% vs 15.9%, p = 0.005).
ABX did not further decrease the end-point; rather, ABX
increased the risk of major bleeding (5.2% vs 2.4% compared
with UFH alone and 8.5% vs 1.9% compared with ENOX
alone). Major bleeding was also increased when half-dose
TNKase was combined with eptifi batide, a small-molecule
GP IIB-IIIA inhibitor in the INTEGRITI study.30 In conjunc-
tion with the GUSTO-V data,31 ASSENT-3, ENTIRE-TIMI-
23 and INTEGRITI indicate that GPIIB-IIIA agents should
not be associated with thrombolytic drugs.
In conclusion, ASSENT-3 and ENTIRE-TIMI 23 showed
that a much simpler thrombolytic regimen is feasible, permit-
ting bolus administration of both TNKase and of adjunctive
low-molecular-weight heparin.
This new regimen was tested in the pre-hospital phase of
STEMI treatment in the ASSENT-3-PLUS study.32 In this
trial, after electrocardiographic confi rmation was obtained
in the fi eld, 1639 patients were treated with TNKase and
randomly allocated to ENOX or UFH adjunctive treat-
ment. Of interest, 53% of patients could be treated in the
fi rst 2 hours, a much higher proportion compared with that
observed in previous studies. In the pre-hospital setting
ENOX tended to reduce the composite of 30-day mortality
or in-hospital reinfarction or in-hospital refractory ischemia
(14.2% vs 17.4%, p = 0.08), but there was no difference in
the effi cacy plus safety end-point, also including the rate of
ICH or major bleeding (18.3% vs 20.3%, p = NS). ENOX
reduced the reinfarction rate (3.5% vs 5.8%, p = 0.028), but
increased the rate of total stroke (2.9% vs 1.3%, p = 0.026)
and of ICH (2.20% vs 0.97%, p = 0.047). The increase in
ICH occurred in the group of patients more than 75 years old.
A pre-specifi ed pooled analysis of data from ASSENT-3
and ASSENT-3-PLUS trials largely confi rmed the utility of
using ENOX instead of UFH in conjunction with TNKase,
reducing the primary effi cacy end-point (composite of death,
reinfarction and refractory ischemia) from 16.0% to 12.2%,
p ⬍ 0.001 and the primary effi cacy plus safety (ICH or
major bleeding) end-point from 18.0% to 15.0%, p = 0.003.33
Among the 1049 patients who required urgent revasculariza-
tion the ENOX benefi cial effect was even larger (15.4% vs
10.1%, p = 0.013). The excess in stroke rates observed with
ENOX (1.3% vs 0.9%), although not signifi cant, was mainly
due to an excess in ICH among women of more than 75 years
old in ASSENT-3-PLUS.
Following these observations, the intravenous bolus of
ENOX was omitted and the maintenance dose was reduced
by 25% in patients of more than 75 years old in the large
defi nitive confi rmation EXTRACT-TIMI 25 trial.15
The role of the routine, immediate use of coronary
angioplasty (so called “facilitated” angioplasty, F-PCI) after
treatment with TNKase was fi rst explored in CAPITAL-
AMI.34 This was a small study randomizing 170 high-risk
STEMI patients treated with TNKase toward immediate
revascularization by PCI or to conservative management.
The primary end-point was the composite of death, rein-
farction, recurrent unstable ischemia, or stroke at 6 months.
The median time from the onset of symptoms to TNKase
administration was 120 minutes and the median time from
symptoms to balloon infl ation 204 minutes. Overall, the pri-
mary end-point was reduced by immediate PCI from 24.4%
to 11.6% (p = 0.04), a result driven mainly by the reduction
in the rate of recurrent unstable ischemia (p = 0.03). There
were no differences in death, reinfarction, stroke or major
bleeding.
These encouraging results stimulated the planning of the
larger ASSENT-4 PCI trial,35 a trial designed to investigate
whether TNKase facilitation would improve the prognosis
of patients for whom a time-delay of 1 to 3 hours before
P-PCI was anticipated. The trial design was open-label and
the primary end-point was the composite of death or con-
gestive heart failure or shock within 90 days. Only 1667 of
the originally planned 4000 patients were enrolled, because
the trial was prematurely interrupted by the data and safety
monitoring board for an excess of in-hospital mortality in
the group where P-PCI was facilitated by TNKase (6% vs
3%, p = 0.0105). The median time from TNKase injection to
fi rst balloon infl ation was 104 minutes. A TIMI-3 fl ow was
achieved before P-PCI in 43% of TNKase-treated patients
and in 15% of patients in the control group (p ⬍ 0.0001).
Vascular Health and Risk Management 2009:5 253
TNKase in acute myocardial infarction
The primary end-point at 90 days was increased in the
facilitated group (19% vs 13%, p = 0.0045), along with the
stroke rate (1.8% vs 0%, p ⬍ 0.0001). These disappointing
results have been attributed, in retrospect, to an alleged
pro-thrombotic effect of TBL and, more convincingly, to
the risk of creating an intra-plaque hemorrhage by infl at-
ing the balloon in the fi rst 2 hours after TBL (ie, in a lytic
state). In retrospect, the risk of death at 90 days was reduced
by TNKase facilitation when patients were randomized in
ambulance (relative risk 0.74, 95% CI 0.24–2.30) and mostly
increased when patients were recruited in P-PCI capable
hospitals (relative risk 1.62, 95% CI 0.94–2.81). These
observation raise important methodological issues about
ASSENT-4 PCI, since 45% patients were actually enrolled
in P-PCI capable hospital, a design not exactly germane as to
defi ne what is the best strategy for the treatment of patients
at the earliest point of care, particularly in the pre-hospital
setting. This holds true particularly when considering that
the trial was open-label.
More pertinent to investigating the role of TNKase
facilitation is the WEST study,36 a randomized, open-label,
feasibility study of 304 STEMI patients enrolled in the com-
munity (40% enrolled pre-hospital). All patients received
aspirin and ENOX and were randomized to either TNKase,
or to TNKase followed by PCI within 24 hours (including
rescue PCI for reperfusion failure) or to P-PCI. The time
from the onset of symptoms to randomization was 113, 130
and 176 minutes respectively. There were no differences
between the three groups in the primary composite of death
or reinfarction, refractory ischemia, congestive heart failure,
cardiogenic shock or major ventricular arrhythmia (25% vs
24% vs 23%, p = NS). In the group receiving plain TNKase
there was a higher rate of the death/reinfarction combination
(13.0% vs 6.7% vs 4.0%, p = 0.021), but not of death (4.0%
vs 1.0% vs 1.0%, p = NS).
Thus, the WEST trial confi rms the data from CAPTIM:9
when delivered very rapidly, possibly in the pre-hospital
phase, TNKase is very competitive with P-PCI and may
offer a very simple and effective treatment, particularly if
subsequent PCI is offered to those patients with recurrent
ischemia or deemed at high clinical risk.
TNKase followed by early routine PCI (within 3–12 hours,
so called “pharmaco-invasive” approach) has been compared
with P-PCI in 212 patients enrolled in the GRACIA-2 study.37
This is a non-inferiority trial designed to evaluate whether
a lytic strategy represents a reasonable option for STEMI
patients, irrespective of geographic or logistic barriers,
when compared with P-PCI. The primary end-points were
epicardial and myocardial reperfusion and the extent of
left ventricular damage (as assessed by infarct size and left
ventricular function). Complete ST-segment resolution at
the electrocardiogram was observed more frequently in
the TNKase group (61% vs 43%, p = 0.01), implying an
improved myocardial perfusion (as measured by the TIMI
myocardial perfusion grade at 60 minutes).38 Infarct size
and left ventricular ejection fraction were similar in the two
groups (Figure 1).
It may be concluded that the results of the WEST study
are confi rmed by GRACIA-2, suggesting the comparable
effi cacy of TNKase (with rescue/routine PCI) and P-PCI.
Most relevant to pathophysiogy and clinical practice, is the
fi nding of GRACIA-2 (in combination with ASSENT-4 PCI)
61 59
43
56
0
10
20
30
40
50
60
70
ST-resolution (%) EF (%)
TNKase + routine PCI P-PCI
p = 0.02 p = NS
Figure 1 ST-segment complete resolution after PCI and left ventricular ejection fraction in GRACIA-2.
P-PCI = Primary angioplasty.
Vascular Health and Risk Management 2009:5
254
Melandri et al
that routine PCI after TNKase should be postponed at least
3 to 12 hours to achieve the benefi t.
Conclusions
TNKase treatment of patients with STEMI is truly evidence-
based.
More than 27,000 patients have been enrolled in several
trials, by different investigators across the world, and address-
ing all major issues: strategy of reperfusion, comparison
with other thrombolytic agents, choice of the best adjunctive
anti-thrombotic treatment, and optimal patient management
after drug injection.
For all the above considerations the American College of
Chest Physicians (ACCP) recognizes TNKase as a Class 1A
recommendation in the treatment of STEMI patients within
12 hours from the onset of symptoms.39
There are indeed several reasons for choosing TNKase
(Table 3): the easy way it may be used in ambulance (this
use is also a Class IA ACCP recommendation), the high
thrombolytic potency with a decreased risk of inducing
major bleeds, and the really competitive results that may be
expected for that majority of patients presenting in the fi rst
3 hours, compared with P-PCI.
Indeed, TNKase is now embraced in many pre-hospital
thrombolytic reperfusion protocols, such as the Vienna
STEMI Registry,40 The Mayo Clinic STEMI Protocol,41 and
The French FAST-MI registry.42
Therefore, a modern, TNKase-based “fi brinolytic strategy”
is now offered to the health care system, which may over-
come the huge logistic problems connected with the utopian,
universal P-PCI implementation.
Pre-hospital TNKase is a real opportunity to offer timely
reperfusion to as many patients as possible in an easy way,
an opportunity that the health care system cannot miss.
Table 4 summarizes how TNKase is used in clinical
practice.
Table 3 Reasons for using TNKase in STEMI patients
TNKase is the most fi brin-specifi c thrombolytic agent available
TNKase may be injected by single intravenous bolus in 5–10 seconds
TNKase is as effective as accelerated rt-PA, but with less major bleeding
Pre-hospital TNKase (with rescue/routine PCI) seems as effective as
primary angioplasty
Table 4 How to use TNKase in STEMI patients
Bolus intravenous injection of TNKase over 5–10 seconds
TNKase dose according to body weight (BW)
30 mg if BW ⬍60.0 kg
35 mg if BW between 60.0 and 69.9 kg
40 mg if BW between 70.0 and 79.9 kg
45 mg if BW between 80.0 and 89.9 kg
50 mg if BW ⱖ90.0 kg
Adjunctive anti-platelet therapy
Aspirin: 160–325 mg, followed by 75–162 mg per day, indefi nitely
Clopidogrel: 75 mg per day (for at least 28 days if no stenting, 1 month
if using a bare metal stent, 1 year if using a drug eluting stent)
Initial clopidogrel dose: 300 mg if age ⱕ75 or if a stent is implanted
Adjunctive unfractionated heparin
Intravenous bolus: 60 U per kg (maximum 4000 U)
Intravenous infusion: 12 U per kg per hour (maximum 1000 U per hour)
Target activated partial thromboplastin time: 1.5–2.0 control
Treatment duration: minimum 48 hours
Adjunctive enoxaparin (only if serum creatinine ⬍2.5 mg/dL in men, ⬍2.0 in women):
Less than 75 years old: Intravenous bolus of 30 mg
Less than 75 years old: Subcutaneous injection of 1 mg/kg every 12 hours
At least 75 years old: No intravenous bolus
At least 75 years old: Subcutaneous injection of 0.75 mg/kg every 12 hours
If the creatinine clearance is ⬍30 mL/min: subcutaneous injection every 24 hours
Treatment duration: for the duration of index hospitalization, up to 8 days
For patients undergoing PCI after TNKase
If on unfractionated heparin: additional boluses as needed
If on enoxaparin: no further anticoagulant if ⬍8 hours from the subcutaneous injection
If on enoxaparin: additional intravenous bolus of 0.3 mg/kg if 8–12 hours
after the subcutaneous injection
Vascular Health and Risk Management 2009:5 255
TNKase in acute myocardial infarction
Disclosures
The authors have no confl icts of interest to disclose.
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