Low-molecular-weight heparin beats unfractionated in STEMI

A new meta-analysis has found that low-molecular-weight heparins (LMWHs) are associated with a reduction in mortality and major bleeding rates in STEMI patients treated with primary PCI as compared with unfractionated heparin (UFH) [1]. And patients at greatest risk seem to derive the most benefit from LMWHs, report Dr Eliano Pio Navarese and colleagues in their paper published online July 20, 2011 in the Journal of Thrombosis and Haemostasis.

heparin

UFH has generally been recognized as the standard anticoagulant for use in STEMI patients undergoing primary PCI, and current AHA/ACC and European Society of Cardiology (ESC) guidelines recommend the use of UFH in this setting, Navarese told heartwire. And although preliminary data from the ATOLL study, which is not yet published, show the efficacy and safety of the LMWH enoxaparin for this use, ATOLL was underpowered to assess the effect of LMWHs on a single outcome such as mortality, he explained.

“But based on our meta-analysis, I would say a new scenario could be envisaged in which LMWH may be considered as a preferred anticoagulant among these patients.”

He added that, to date, there has been no comparison of LMWHs with another newer strategy for primary PCI in STEMI, the use of bivalirudin (Angiomax, the Medicines Company), “which in HORIZONS-AMI has been shown to be superior to UFH and GP IIb/IIIa inhibitors in STEMI. This is a black hole we have to date. However, I am not convinced that bivalirudin spells the end of other anticoagulants in PCI for STEMI, as some uncertainty remains in the early phase of primary PCI, when thrombotic complications seem to be higher with bivalirudin monotherapy.”

But Navarese says, in any case, ideally, “the next step should be to move toward personalized anticoagulant therapy in primary PCI, where a stratification of thrombotic and bleeding risk of each patient could guide the choice of the proper anticoagulant regimen.”

LMWH resulted in 50% fewer deaths than UFH

Navarese et al performed two separate meta-analyses of available studies comparing LMWHs with UFH in STEMI patients treated with primary PCI as well as those treated with PCI after thrombolysis. The LMWH most commonly used in the studies was enoxaparin, he said. He notes that this is the first meta-analysis to assess the efficacy and safety of LMWHs over UFH in the setting of PCI for STEMI.

I would say a new scenario could be envisaged in which LMWH may be considered as a preferred anticoagulant.

Ten studies, including ATOLL, comprising 16 286 patients, were included, with a median follow-up of two months. All-cause mortality was the prespecified primary end point, and major bleeding complications were a secondary end point.

In primary PCI, LMWH was associated with a reduction in mortality (risk reduction 0.51; p<0.001) and a reduction in major bleeding (RR 0.68; p=0.02) compared with UFH. And meta-regression showed that patients with higher baseline risk had greater benefits with LMWHs (r=0.72, p=0.02).

Navarese—who is a fellow of the ESC European Association of Percutaneous Cardiovascular Interventions (FEAPCI) Working Group on Thrombosis—says the results of this meta-analysis, “mostly based on patients taken from the real world, are reliable based on adjusted and stratified analysis.”

And he notes that, theoretically, from a pharmacological standpoint, there are a number of reasons why LMWH may be better suited to STEMI patients undergoing primary PCI than UFH. First, LMWHs have greater activity against activated factor Xa, he says, and “a much more predictable anticoagulant response than UFH.” And LMWHs “have pleiotropic effects that may also contribute to their superior anticoagulant effects.”

No clear evidence that LMWHs are better than UFH in lytic studies

In contrast, Navarese and colleagues found no clear evidence of an advantage of LMWHs over UFH in the PCI group after thrombolysis.

Navarese said a potential explanation for this finding is the fact that, in the setting of primary PCI, LMWHs are predominantly administered intravenously and for a short duration, whereas in the lytic studies, they were generally given subcutaneously and for a prolonged period.

“It is very important that future randomized controlled trials with longer follow-up should investigate the recommended route of administration and dosage of LMWHs in this setting,” he observed.

Coauthors Dr Paul Gurbel (Sinai Hospital, Baltimore, MD) and Dr C Michael Gibson (Harvard Medical School, Boston, MA) report research grant support and  consultancy from Sanofi-Aventis, not related to the present work. The other authors have no conflict of interests.
  1. Navarese EP, De Luca G, Castriota F, et al. Low-molecular-weight heparins vs unfractionated heparin in the setting of percutaneous coronary intervention for ST-elevation myocardial infarction: A meta-analysis. J Thromb Haemost 2011; DOI: 10.1111/j.1538-7836.2011.04445.x. Available at: http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1538-7836

JULY 29, 2011 

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