como adyuvante de la trombólisis coronaria.
1: Eur Heart J
reperfusion and clinical outcome with enoxaparin as an adjunct to streptokinase
thrombolysis in acute myocardial infarction. The AMI-SK study.
Krzeminska-Pakula M, Alonso A, Goodman S, Kali A, Loos U, Gosset F,
Louer V, Bigonzi
Erasmus University Medical Center, Rotterdam, The Netherlands
establish whether the addition of enoxaparin (a low-molecular-weight heparin)
to streptokinase therapy improves early and sustained coronary patency and
clinical outcome in patients with evolving myocardial infarction.Methods
and Results A total of 496 patients with acute
myocardial infarction treated with streptokinase
were randomized to an intravenous bolus (30mg) and subcutaneous injections
(1mg.kg(-1), twice daily) of enoxaparin (n=253), or placebo (n=243) for
3-8 days. The median duration of treatment in both groups was 5 days. ST-segment
resolution at 90min and 180min measured by electrocardiogram was improved
in patients receiving enoxaparin. Complete, partial and no ST-segment resolution
at 180min was observed in 36%, 44% and 19% in the enoxaparin group vs 25%,
44% and 31% in the placebo group, respectively (P=0.004). Assessment of
the primary end-point revealed improved TIMI-3 flow
with enoxaparin vs placebo (70% vs 58%, P=0.01).
Combined TIMI-2 and -3 flow was also improved (88% vs 72%, P=0.001),
as was TIMI frame count (P=0.003). The triple clinical end-point of death,
reinfarction and recurrent angina at 30 days was reduced with enoxaparin (13%
vs 21%, P=0.03).ConclusionStreptokinase in combination with enoxaparin is associated
with better ST-segment resolution and better angiographic patency at days
5-10, suggesting more effective reperfusion. This was associated with a significant
reduction in clinical events, indicating less reocclusion.
update of its clinical use in the management of acute coronary syndromes.
Ibbotson T, Goa
International Limited, Auckland, New Zealand. email@example.com
sodium) is a low molecular weight heparin (LMWH) indicated
for use in the treatment of ischaemic complications of unstable angina and
non-Q wave myocardial infarction (MI). Unfractionated heparin (UFH) has
for many years represented the standard in
anticoagulant therapy for patients with acute
coronary syndromes; however, recent studies suggest that enoxaparin is also
a viable option for anticoagulant therapy in these patients. The ESSENCE (Efficacy
and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events) and
the TIMI 11B (Thrombolysis in Myocardial Infarction) studies reported that
twice daily enoxaparin was significantly more
effective than a continuous infusion of UFH in
reducing the composite triple endpoint of death, MI, or recurrent
angina or urgent revascularisation. Follow-up of both patient populations
showed continued benefit associated with enoxaparin. Enoxaparin has been
compared with tinzaparin in the treatment of unstable coronary artery disease
using a nonblind study design. There was no difference between treatment groups
in the therapeutic endpoints. Three nonblind studies have also compared the
effects of enoxaparin and UFH in patients receiving thrombolytic therapy following
acute MI. The HART II (Heparin and Aspirin Reperfusion Therapy), the ASSENT
3 (Assessment of the Safety and Efficacy of a New Thrombolytic Regimen) and
the ENTIRE-TIMI 23 (Enoxaparin and Tenecteplase with or without
glycoprotein IIb/IIIa Inhibitor as Reperfusion
strategy in ST Elevation MI - Thrombolysis in Myocardial
Infarction) studies have revealed that enoxaparin in combination with alteplase
or tenecteplase is at least equivalent (HART II and ENTIRE-TIMI 23), and
possibly superior (ASSENT 3) to UFH. Enoxaparin is administered as a twice-daily
subcutaneous injection. In contrast, UFH is administered as an intravenous
infusion which requires routine monitoring of the activated partial thromboplastin
time to ensure adequate levels of anticoagulation are maintained. During
the acute phase of the the ESSENCE and TIMI 11B studies, the incidence of major
bleeding was similar in patients receiving enoxaparin to that in patients receiving
UFH. In contrast, the rates of minor bleeding were higher in patients receiving
enoxaparin than in those receiving UFH throughout these studies. Conclusions:
Data from the ESSENCE, TIMI 11B and ASSENT 3 studies have prompted calls
for those LMWHs which have been shown to be superior to UFH, to be considered
as first choice treatment for anticoagulation in unstable coronary syndromes.
To date, these suggestions are not reflected in current guidelines which
consider UFH and LMWHs equally. Irrespective, the clinical data reported in
this review support the use of enoxaparin in the treatment of acute
coronary syndromes. These data suggest that
enoxaparin shows certain clinical and practical
advantages over standard treatment with UFH and represents an important
development in the treatment of acute coronary syndromes.
3: Curr Opin
Cardiol 2001 Nov;16(6):384-9
The role of low-molecular-weight
heparin in the management of acute coronary syndromes.
Cardiology, MCP-Hahnemann School of Medicine, Philadelphia, Pennsylvania
19102-1192, USA. firstname.lastname@example.org
medical treatment for the non-ST segment elevation acute coronary syndromes
(NSTE ACS) should consist of a combined antithrombotic/anti-anginal regimen.
Standard antithrombotic treatment is currently unfractionated heparin and
aspirin, and in high-risk patients glycoprotein IIb/IIIa inhibitors. However,
low-molecular-weight heparins (LMWHs) have practical and clinical advantages
over UFH and can be considered an effective alternative in the medical
treatment of ACS and in patients proceeding to surgical interventions. Benefits
include a more predictable and stable therapeutic response, no need for coagulation
monitoring and a reduced incidence heparin-induced thrombocytopenia. In
this context, the LMWH enoxaparin has demonstrated sustained clinical and economic
benefits compared with UFH, with no increase in major bleeding complications.
In addition, recently published studies indicate that LMWHs can improve
reperfusion of the arteries and reduce reocclusion when used as adjunctive
anticoagulant therapy in patients with ST segment elevation (STE) ACS undergoing
thrombolysis with fibrin-specific agents or streptokinase.
4: Lancet 2001
safety of tenecteplase in combination with enoxaparin, abciximab, or
unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction.
of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3
Current fibrinolytic therapies fail to achieve optimum reperfusion in
many patients. Low-molecular-weight heparins and platelet glycoprotein IIb/IIIa
inhibitors have shown the potential to improve pharmacological reperfusion
therapy. We did a randomised, open-label trial to compare the efficacy
and safety of tenecteplase plus enoxaparin or abciximab, with that of tenecteplase
plus weight-adjusted unfractionated heparin in patients with acute myocardial
infarction. METHODS: 6095 patients with acute myocardial infarction of
less than 6 h were randomly assigned one of three regimens: full-dose tenecteplase
and enoxaparin for a maximum of 7 days (enoxaparin group; n=2040), half-dose
tenecteplase with weight-adjusted low-dose unfractionated heparin and a
12-h infusion of abciximab (abciximab group; n=2017), or full-dose tenecteplase
with weight-adjusted unfractionated heparin for 48 h (unfractionated
heparin group; n=2038). The primary endpoints were the composites
of 30-day mortality, in-hospital reinfarction, or in-hospital refractory
ischaemia (efficacy endpoint), and the above endpoint plus in-hospital
intracranial haemorrhage or in-hospital major bleeding complications (efficacy
plus safety endpoint). Analysis was by intention to treat. FINDINGS: There
were significantly fewer efficacy endpoints in the enoxaparin and abciximab
groups than in the unfractionated heparin group: 233/2037 (11.4%) versus
315/2038 (15.4%; relative risk 0.74 [95% CI 0.63-0.87], p=0.0002) for enoxaparin,
and 223/2017 (11.1%) versus 315/2038 (15.4%; 0.72 [0.61-0.84], p<0.0001)
for abciximab. The same was true for the efficacy plus safety endpoint:
280/2037 (13.7%) versus 347/2036 (17.0%; 0.81 [0.70-0.93], p=0.0037) for
enoxaparin, and 287/2016 (14.2%) versus 347/2036 (17.0%; 0.84 [0.72-0.96],
p=0.01416) for abciximab. INTERPRETATION: The
tenecteplase plus enoxaparin or abciximab regimens
studied here reduce the frequency of ischaemic complications of
an acute myocardial infarction. In light of its ease of administration, tenecteplase
plus enoxaparin seems to be an attractive alternative reperfusion regimen
that warrants further study.
2001 Aug 7;104(6):648-52
comparison of enoxaparin, a low-molecular-weight heparin, with unfractionated
heparin adjunctive to recombinant tissue plasminogen activator thrombolysis
and aspirin: second trial of Heparin and Aspirin Reperfusion Therapy
Ross AM, Molhoek
P, Lundergan C, Knudtson M, Draoui Y, Regalado L, Le Louer V, Bigonzi
F, Schwartz W, de Jong E, Coyne K; HART II Investigators.
Research Institute, Institute of Medicine, George Washington University,
Washington, DC, USA. email@example.com
Adjunctive unfractionated heparin (UFH) during thrombolytic therapy for
acute myocardial infarction (AMI) promotes the speed and magnitude of coronary
artery recanalization and reduces reocclusion. Low-molecular-weight heparins
offer practical and potential pharmacological advantages over UFH in multiple
applications but have not been systematically studied as adjuncts to fibrinolysis
in AMI. METHODS AND RESULTS: Four hundred patients undergoing reperfusion
therapy with an accelerated recombinant tissue plasminogen activator regimen
and aspirin for AMI were randomly assigned to receive adjunctive therapy for
at least 3 days with either enoxaparin or UFH. The study was designed to show
noninferiority of enoxaparin versus UFH with regard to infarct-related artery
patency. Ninety minutes after starting therapy, patency rates (thrombolysis
in myocardial infarction [TIMI] flow grade 2 or 3) were 80.1% and 75.1%
in the enoxaparin and UFH groups, respectively. Reocclusion at 5 to 7 days
from TIMI grade 2 or 3 to TIMI 0 or 1 flow and TIMI
grade 3 to TIMI 0 or 1 flow, respectively, occurred
in 5.9% and 3.1% of the enoxaparin group versus 9.8% and 9.1%
in the UFH group. Adverse events occurred with similar frequency in both treatment
groups. CONCLUSIONS: Enoxaparin was at least as effective as UFH as an adjunct
to thrombolysis, with a trend toward higher recanalization rates and less
reocclusion at 5 to 7 days.
6: Thromb Res
2001 May 1;102(3):261-71
enoxaparin over heparin in combination with a GPIIb/IIIa receptor antagonist
during coronary thrombolysis in dogs.
Kasiewski CJ, Bentley RG, Morgan SR, Chu V, Bostwick JS, Klein SI, Perrone
MH, Leadley RJ.
Biology, Aventis Pharmaceuticals, 19426, Collegeville, PA, USA. firstname.lastname@example.org
It is known that
a low-molecular-weight heparin (LMWH) is more effective than unfractionated
heparin in unstable angina/non-Q-wave myocardial infarction (UA/NQMI)
and the platelet GPIIb/IIIa receptors play an important role in acute myocardial
infarction (AMI). Therefore, enoxaparin might have a similar advantage
over heparin when used with a GPIIb/IIIa antagonist (RPR109891) in coronary
thrombolysis. After induction of coronary thrombosis in anesthetized dogs,
infusion of saline, enoxaparin, heparin, RPR109891, enoxaparin+RPR109891, or
heparin+RPR109891 was initiated followed 15 min later by recombinant
tissue plasminogen activator (rt-PA). The incidence
of reperfusion in the enoxaparin+RPR109891- and the
heparin+RPR109891-treated groups was similar, but time
to reperfusion tended to be shorter for enoxaparin versus heparin. Only
43% of the vessels reoccluded in the
enoxaparin+RPR109891 group, compared to 100% vessels
in the heparin+RPR109891 group. Enoxaparin+RPR109891 maintained flow for a
significantly longer time compared to saline, enoxaparin, heparin, and heparin+RPR109891.
Enoxaparin+RPR109891 and heparin+RPR109891 increased the template
bleeding time by 2- and 3-fold and activated partial thromboplastin time
(APTT) by 1.3- and 3-fold, respectively. These data suggest that
enoxaparin is more effective and potentially safer
than heparin when combined with a GPIIb/IIIa
receptor antagonist during rt-PA-induced coronary thrombolysis.
7: J Invasive
Cardiol 2000 Dec;12 Suppl D:16D-8D
of eptifibatide and enoxaparin in the medical management of a patient
with a non-ST segment elevation acute coronary syndrome and in-stent restenosis.
Benzuly K, Fintel D.
University School of Medicine, Coronary Care Unit, Wesley Suite 726,
250 East Superior Street, Chicago, IL 60611, USA.
8: J Thromb
Thrombolysis 2000 Dec;10(3):241-6
The TETAMI trial:
the safety and efficacy of subcutaneous enoxaparin versus intravenous
unfractionated heparin and of tirofiban versus placebo in the treatment
of acute myocardial infarction for patients not thrombolyzed: methods and
Cohen M, Maritz
F, Gensini GF, Danchin N, Timerman A, Huber K, Gurfinkel EP, White
H, Fox KA, Vittori L, Le-Louer V, Bigonzi F.
University Hospital, Philadelphia, Pennsylvania 19102-1192, USA. email@example.com
acute myocardial infarction (AMI) who do not receive early reperfusion
therapy are at high risk of reinfarction or death, and the efficacy and
safety of antithrombotic therapy in this group of patients has not been evaluated.
Enoxaparin is a low-molecular-weight heparin (LMWH) that has previously
been shown to reduce the incidence of ischemic events in patients with
unstable angina or non-Q-wave MI. The principal aims of the TETAMI study are
to investigate the efficacy and safety of treatment with enoxaparin or tirofiban
(a glycoprotein IIb/IIIa receptor antagonist) alone or in combination for
2 to 8 days in patients with AMI who are not eligible for early
reperfusion therapy. In this 2 by 2 factorial design
study approximately 900 patients will be randomly
assigned, in a blinded manner, to one of four treatments: enoxaparin alone,
enoxaparin plus tirofiban, unfractionated heparin (UFH), or UFH plus tirofiban,
with appropriate matched placebos. The primary end point is the composite
of death, recurrent AMI, and recurrent angina, analyzed at 30 days after
AMI. The design and methods of the TETAMI study are described in this article.
9: Arch Mal
Coeur Vaiss 2000 Jan;93(1 Spec No):77-81
The best of
thrombosis and thromboembolic disease in 1999
cardiologie, Hopital Pasteur, Nice.
1999 has been a
good year in the field of innovation in thrombosis. In coronary syndrome
without ST elevation: low molecular weight heparin has been confirmed to
be more effective than non-fractionated heparin (enoxaparin) and to
improve the prognosis of non-revascularised patients
(dalteparin) after the hospital phase; hirudin has
been shown to be more effective in terms of incidence of myocardial
infarction and recurrence of angina than non-fractionated heparin without
a higher incidence of bleeding complications; the anti-GP IIb-IIIa (abciximab)
has confirmed all its advantages at 6 months and 1 year after a coronary
event. The association of heparin and aspirin, which has been the mainstay
of antithrombotic treatment of acute coronary syndromes without ST elevation,
will soon be improved upon at the beginning of the third millennium. In
myocardial infarction, medical thrombolysis has probably reached a turning
point in its history. The association of half doses
of rt-Pa and anti-GP IIb-IIIa has been shown to be
more effective in obtaining good reflow than the thrombolytic
agent alone at conventional doses. These results were obtained without
any increase in bleeding complication. The same anti-GP IIb-IIIa also improve
mechanical revascularisation by optimising reperfusion after the 24th hour.
This benefit is rapidly transformed into reduced left ventricular dysfunction.
Pulmonary embolism remains a critical illness as the ICOPER registry
reports a 3 year mortality of nearly 16%. This emphasises the importance
of early diagnosis which is usually possible without resorting to invasive
procedures and by modulating all the results of paraclinical investigations
with respect to the pretest clinical probability.
10: J La State
Med Soc 1999 May;151(5):272-7
Advances in the
pathogenesis and treatment of acute coronary syndromes.
Danzell JD, Hanley HG.
Internal Medicine, Louisiana State University School of Medicine, Shreveport,
entities of unstable angina, non-Q wave myocardial infarction, and Q
wave myocardial infarction share the same pathogenesis and, because of
this, are linked under the heading of acute coronary
syndromes. Prompt reperfusion in the early phase of
acute ST segment elevation myocardial infarction, with thrombolysis
or percutaneous transluminal coronary angioplasty, now has an established
place in the treatment of this condition. However, thrombolysis has been
disappointing and may be harmful in the treatment of unstable angina and non-Q
wave myocardial infarction. While traditional therapy with morphine, oxygen,
nitrates, aspirin, heparin, and beta blockers may be indicated in the treatment
of all types of acute coronary syndromes, recent studies have led to advances
in the treatment of unstable angina/non-Q wave myocardial infarction patients.
In these patients, enoxaparin (a low molecular weight heparin) and the platelet
glycoprotein IIb/IIIa receptor antagonists may be particularly effective.