Low-molecular-weight heparins in coronary stenting (the ENTICES trial)

doi:10.1016/S0002-9149(98)00110-6

The American Journal of Cardiology

Volume 82, Issue 5, Supplement 2, 10 September 1998, Pages 29L-32L

https://doi.org/10.1016/S0002-9149(98)00110-6 Get rights and content

Abstract

The role of low-molecular-weight heparins (LMWHs) in the management of stent thrombosis, although expected to produce fewer hemorrhagic complications than warfarin anticoagulation regimens, is poorly defined. The ENoxaparin and TIClopidine after Elective Stenting (ENTICES) trial was designed to compare a combination of a LMWH (enoxaparin), ticlopidine, and aspirin with the conventional warfarin anticoagulant treatment in patients who received coronary stents, in an effort to decrease stent thrombosis and ischemic clinical events. The results show that the enoxaparin regimen produced significantly fewer clinical events and vascular complications than the conventional warfarin anticoagulant regimen.

Section snippets

Study design

A total of 123 patients were enrolled over a 7-month period at 7 sites in the United States. The entry criteria into the study are given in Table I

At the time of the study, all of the participating sites were using the conventional anticoagulation regimen (aspirin, dipyridamole, intravenous heparin, and warfarin). To spur recruitment, patients were randomized 2 : 1, weighted in favor of the enoxaparin/ticlopidine/aspirin regimen versus the conventional regimen.

The primary endpoint consisted of

Angiographic data

All patients in both groups had good left ventricular function (median ejection fractions of 60% [25th–75th percentile, range 50–65] and 60% [50–66] for the conventional and enoxaparin groups, respectively). Most lesions were of intermediate difficulty (class B lesions, according to the American College of Cardiology and the American Heart Association classification).6 A few patients had dissections that had not been reported by the investigators at the site, and there was evidence, at least in

Discussion

This trial has demonstrated that the combination of enoxaparin, ticlopidine, and aspirin after elective stenting is a well-tolerated and effective treatment strategy to decrease ischemic complications and hemorrhagic vascular complications after elective coronary stent placement, when compared with the conventional warfarin anticoagulation regimen. At 30 days, the ischemic endpoints were decreased with the enoxaparin regimen compared with the conventional regimen and were consistent across all

Acknowledgements

The author wishes to acknowledge support from the following sources: the US Food and Drug Administration, Rhône-Poulenc Rorer, and Mallinckrodt.

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Although upstream use of LMWH in ACS is accepted, the strategy of continued LMWH therapy after PCI is much less well established. In a number of studies evaluating this question, in terms of reduced restenosis and subacute stent thrombosis, particularly in the setting of dual antiplatelet therapy, LMWH has not seemed to provide any additional benefit [111–115]. It is therefore not routinely recommended.
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The purpose of this article is to evaluate the use of perioperative antithrombotics in patients undergoing surgical revascularization of the coronary vessels. Although there is a general agreement about the use of anticoagulation during off-pump coronary revascularization (OPCAB), the degree of the required anticoagulation varies from one center to another. The review is divided into four major sections. The first section describes the pathophysiology of the coagulation system in cardiac surgery with and without the use of cardiopulmonary bypass. In this section, we also discuss the interactions between the coagulation system and the inflammatory response to cardiac surgery. The second section examines the role of prophylactic antithrombosis in patients referred to surgical revascularization, and their role in bleeding complications associated with surgery. Heparinization and neutralizing its anticoagulative effects during coronary surgery are discussed in the third section. The fourth section examines the evidence that the inflammatory response contributes to adverse peri-operative events, in particular organ dysfunction, and potential therapeutic strategies to control this response. The review concludes with a summary of potential future research directions and key deficiencies in our knowledge regarding the use of anticoagulants in cardiac surgery.
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After the coronary intervention, a combination of aspirin and ticlopidine has been shown to be superior to either aspirin alone or aspirin and warfarin in preventing stent thrombosis.58,59 In a pilot study, a regimen of LMWH, ticlopidine, and aspirin was shown to be more effective than warfarin in decreasing thrombosis and ischemic clinical events after stent placement.60 Patients at a high risk for thrombosis normally receive a combination of aspirin, warfarin, and clopidogrel.
Patients receiving chronic anticoagulation therapy pose a clinical challenge when therapy needs to be interrupted for surgical or invasive procedures. Maintaining anticoagulation places them at risk for serious bleeding complications, whereas discontinuing anticoagulation puts them at risk of thromboembolic complications. Most patients can undergo dental procedures, cataract surgery, and diagnostic endoscopy without discontinuing anticoagulation. The main patient groups that may require a periprocedural alternative to oral anticoagulation (periprocedural thromboprophylaxis or bridging) include patients with prosthetic heart valves, atrial fibrillation, and hypercoagulable states and patients with chronic venous thrombosis who are undergoing surgery. Currently, there is little consensus on the appropriate perioperative treatment of patients on long-term warfarin therapy. There are an increasing number of studies that evaluate the benefits of periprocedural bridging with low-molecular-weight heparin (LMWH) in place of unfractionated heparin (UFH). An advantage of LMWH over UFH is that perioperative conversion from warfarin therapy with LMWH can be carried out in the outpatient setting, which is more convenient for patients and is cost effective. As with the use of UFH, there are reports of maternal thromboembolic complications with LMWHs in pregnant women with mechanical heart valves. This review brings together the available data on periprocedural bridging to assess the available options for patients on long-term warfarin therapy who are undergoing surgical procedures. It provides a rationale for using LMWHs while individualizing the risks versus benefits in a given patient population.
Postprocedural low molecular weight heparin in patients at high risk of subacute stent thrombosis
2003, Cardiovascular Radiation Medicine
Subacute stent thrombosis (SAT) is a dramatic complication of percutaneous coronary stenting occurring in 0.4–20% of cases depending on several angiographic and clinical variables. The role of postprocedural low molecular weight heparin (LMWH) in preventing early events after high-risk PCI is not well established. In this study we describe our experience with postprocedural LMWH in patients deemed to be at high risk of SAT.
Thirty-six patients who were treated with subcutaneous LMWH for at least 7 days after the intervention were identified from our database. All cineangiograms and charts were retrospectively reviewed to confirm the high-risk intervention properties. Thirty-day and long-term major adverse coronary events (MACEs) were documented in all patients.
The most common indications for LMWH were the deployment of ≥3 consecutive stents, the presence of intracoronary thrombus or ulceration, poststenting residual stenosis, contraindication to aspirin or thienopyrideines, and persistent dissection. The majority of patients (61%) had ≥2 risk factors. Mean postprocedural treatment period was 12±3 days. At 30 days, none of the patients experienced a MACE including death, myocardial infarction, and repeat revascularization. No major bleeding occurred and one patient (2.7%) had a minor bleeding. At a mean follow-up of 31 months, MACE occurred in 17% of patients.
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Enoxaparin may reduce the risk of myocardial infarction among people at increased risk of stent thrombosis, but is unnecessary for most people
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Original ArticlesLow-molecular-weight heparins in coronary stenting (the ENTICES trial)

Abstract

Section snippets

Study design

Angiographic data

Discussion

Acknowledgements

J Am Coll Cardiol

Lancet

Antiplatelet versus warfarin therapyplatelet, neutrophil, and thrombus deposition for intracoronary stents in a procine model

J Interven Cardiol

Ticlopidine and subcutaneous heparin as an alternative regimen following coronary stenting

Cathet Cardiovasc Diagn

Original Articles
Low-molecular-weight heparins in coronary stenting (the ENTICES trial)