Prof. Steen Dalby Kristensen,
The investigators studied whether enoxaparin is superior to unfractionated heparin (UFH) as adjunctive therapy for fibrinolytic therapy. The study was carried out among ST-elevation myocardial infarction (STEMI) patients, who subsequently underwent percutaneous coronary intervention (PCI).
A total of 20,479 subjects for whom fibrinolysis was planned were randomised to - a strategy of enoxaparin throughout the index hospitalisation or - weight-based UFH for 48 hours in a double-blind manner, with blinded study drug to continue if PCI was performed before day 8 or hospital discharge.
In this pre-specified study, the primary efficacy end point of death or nonfatal recurrent myocardial infarction through 30 days was compared for enoxaparin vs UFH among patients who underwent PCI (n=4,676).
Results: Fewer patients underwent PCI following the administration of enoxaparin vs UFH through 30 days (22.8% vs 24.2%, p=0.027).
RR (95% CI)
As shown above, enoxaparin administration for the duration of the index hospitalisation was associated with a reduced 30 day risk of the composite of death, recurrent MI, and stroke compared to UFH administered for 48 hours. These advantages of enoxaparin were observed without an increase in the risk of major bleeding, consistent with a significant net clinical benefit in favor of enoxaparin. These favorable outcomes were also evident in the cohort of patients who underwent PCI while on blinded study drug. Enoxaparin is a good option after thrombolysis up to and during a subsequent PCI.
Out-of-hospital cardiac arrest (CA) comprises a cascade of events with no specific treatment beyond cardio-pulmonary resuscitation (CPR), but with mortality as high as 95%. Up to 70% of CA patients have underlying acute myocardial infarction or pulmonary embolism. Both conditions are potentially responsive to fibrinolytic therapy, as demonstrated in small trials/observational studies.
This was the rationale for the TROICA trial. 1,050 patients suffering from witnessed out-of-hospital arrest of presumed cardiac origin were randomly assigned to tenecteplase (TNK) or placebo, plus standard therapy for CA.
The ITT analysis showed that the addition of TNK to standard CPR did not increase the 30-day survival rate (18.2% vs. 20.2%, NS) nor the hospital admission rate (59.0% vs. 59.5%, NS). The symptomatic intracranial haemorrhage (1% vs. 0%) and major bleeding (8.9% versus 7.4%) rates were not significantly different between groups.
Possible explanations for these unexpected results: inappropriate timing of TNK administration (too early/too late); negative interactions (e.g., vasopressors, pH, etc.); and lack of adjunctive antithrombotic therapy. The study does not support the routine use of thrombolysis in refractory CA.
Patients with peripheral atherosclerotic disease from 80 centers in 7 countries were randomised to receive either - antiplatelet therapy only (n=1,081) or - antiplatelet therapy combined with oral anticoagulants (n=1,080).
Patients with peripheral atherosclerotic disease are at increased risk of late cardiovascular events and the combined strategy has been shown to be effective in patients with CVD. The aspirin dose varied between 81 and 325 mg. The oral anticoagulant therapy was of moderate intensity aiming at an INR 2-3.
Results after 42 months follow-up showed that 12.2% of patients with combined therapy suffered cardiovascular death, infarction or stroke compared to 13.3% of patients receiving aspirin only (P=0.49). In addition, 4% of the patients with combined therapy experienced life-threatening bleeds compared to 1.2% in the aspirin only group (P<0.001). It was concluded that the combined therapy offered no beneficial effect (and a higher bleeding risk) in patients with peripheral atherosclerotic disease.
The OASIS-5 (N=20,000) and OASIS-6 (N=12,000) randomized trials demonstrated reductions in all-cause mortality and bleeding with fondaparinux compared with standard care in patients with unstable angina/NSTEMI and STEMI, respectively. When combining the data from these two mega-trials, Mehta and coworkers showed that fondaparinux is superior to UFH/enoxaparin in reducing death/MI/stroke across the whole spectrum of patients with ACS, and is associated with markedly lower rates of major bleeding than UFH/enoxaparin.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
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Dr. S. D. Kristensen, Aarhus, Denmark Past-chairman of the ESC WG Thrombosis
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