Elsevier

The Lancet

Volume 352, Issue 9129, 29 August 1998, Pages 673-681
The Lancet

Articles
Randomised comparison of implantation of heparin-coated stents with balloon angioplasty in selected patients with coronary artery disease (Benestent II)

https://doi.org/10.1016/S0140-6736(97)11128-XGet rights and content

Summary

Background

The multicentre, randomised Benestent-II study investigated a strategy of implantation of a heparincoated Palmar-Schatz stent plus antiplatelet drugs compared with the use of balloon angioplasty in selected patients with stable or stabilised unstable angina, with one or more de-novo lesions, less than 18 mm long, in vessels of diameter 3 mm or more.

Methods

827 patients were randomly assigned stent implantation (414 patients) or standard balloon angioplasty (413 patients). The primary clinical endpoint was event-free survival at 6 months, including death, myocardial infarction, and the need for revascularisation. The secondary endpoints were the restenosis rate at 6 months and the cost-effectiveness at 12 months. There was also one-to-one subrandomisation to either clinical and angiographic follow-up or clinical follow-up alone. Analyses were by intention to treat.

Findings

Four patients (one stent group, three angioplasty group) were excluded from analysis since no lesion was found. At 6 months, a primary clinical endpoint had occurred in 53 (12·8%) of 413 patients in the stent group and 79 (19·3%) of 410 in the angioplasty group (p=0·013). This significant difference in clinical outcome was maintained at 12 months. In the subgroup assigned angiographic follow-up, the mean minimum lumen diameter was greater in the stent group than in the balloon-angioplasty group, (1·89 [SD 0·65] vs 1·66 [0·57] mm, p=0·0002), which corresponds to restenosis rates (diameter stenosis ≥50%) of 16% and 31% (p=0·0008). In the group assigned clinical follow-up alone, event-free survival rate at 12 months was higher in the stent group than the balloon-angioplasty group (0·89 vs 0·79, p=0·004) at a cost of an additional 2085 Dutch guilders (US$1020) per patient.

Interpretation

Over 12-month follow-up, a strategy of elective stenting with heparin-coated stents is more effective but also more costly than balloon angioplasty.

Introduction

After the publication of Benestent-11 and STRESS2, two randomised trials that compared elective stenting with balloon angioplasty, there was concern3 about the risk of subacute occlusion, bleeding, and vascular complications associated with intensive antithrombin therapy, as well as about cost increases stemming from stents, adjunctive balloons, and longer hospital stays, although no prospectively collected data on costs were available in these trials. In addition, the homogeneous cohort of patients with stable disease tested in Benestent-I was not representative of the unselected patients treated in routine practice.

The design of this study, Benestent-II, aimed to address these various issues. Attention was directed to coating the stent with a material that would lower the risk of abrupt stent closure and obviate the need for anticoagulant therapy, thereby reducing bleeding complications as well as the duration of hospital stay. A heparin-coated stent was tested in the Benestent-II pilot study, in which anticoagulation with a coumadine analogue was replaced by antiplatelet therapy in a stepwise manner.4 This pilot study confirmed that anticoagulant therapy could be withdrawn safely and showed that the heparin-coated stent in combination with two-pronged antiplatelet treatment virtually eliminated the risk of subacute stent thrombosis and resulted in a favourable event-free survival (86%) after 6 months. Gawaz and colleagues5 have shown that anticoagulation with anti-vitamin K and heparin does not prevent the activation of the IIB/IIIA receptors on the platelets, whereas the combination of ticlopidine and aspirin achieves this goal, thereby greatly reducing the incidence of subacute occlusion, a thrombotic event triggered mainly by platelet aggregation. Furthermore, full deployment of the stent by high-pressure balloon inflation under intravenous ultrasonographic guidance has reduced the risk of subacute occlusion.6

The Benestent-II study was designed to test the hypothesis that use of a heparin-coated stent plus antiplatelet therapy would result in better event-free survival at 6 months than that resulting after standard balloon angioplasty. Secondary analyses were planned to compare restenosis rate at 6 months and cost-effectiveness at 12 months for the two interventions. Although savings can be expected if there is a reduction in repeat revascularisation procedures, there are still questions of whether these savings will compensate for the higher initial costs and, if this is not the case, how the additional benefits weigh against the additional costs.7, 8

Section snippets

Selection of patients

Eligible patients were those scheduled to undergo coronary angioplasty, who had one or more de-novo lesions due to stable angina or unstable angina (Braunwald class IB, IIB, IC, IIC),9 who had no contraindication to platelet therapy with aspirin and ticlopidine, and who were suitable candidates for coronarybypass surgery. The protocol required that all the target lesions (if multiple) were suitable for stent implantation (< 18 mm in length and located in a vessel of diameter >3·00 mm, supplying

Characteristics of patients

Between September, 1995, and March, 1996, 827 patients were randomly assigned stent implantation (414 patients) or balloon angioplasty (413 patients) at 50 participating centres (figure 1). Four patients were excluded from the intention-to-treat analysis because they did not undergo coronary revascularisation; their lesions were shown to be physiologically non-significant during on-line quantitative coronary angiography at the time of the intended intervention. The 1-year follow-up of these

Discussion

This study confirms that stenting has a preventive effect on restenosis. It also confirms that the combined use of two antiplatelet drugs, aspirin and ticlopidine, is safe and effective in preventing stent thrombosis.22

Although this trial was not specifically designed to investigate the value of the heparin coating, among the 721 patients (with various ischaemic syndromes including acute myocardial infarction23) who have received heparin-coated stents, only one patient has so far presented with

References (31)

  • B Van Hout et al.

    Cost effects and C/E-ratios alongside a clinical trial

    Health Economics

    (1996)
  • E Braunwald

    Unstable angina: a classification

    Circulation

    (1989)
  • PW Serruys et al.

    Angiographic follow-up after placement of a self-expanding coronary-artery stent

    N Engl J Med

    (1991)
  • H Blackburn et al.

    The electrocardiogram in population studies: a classification system

    Circulation

    (1960)
  • BA Van Hout et al.

    Costs and effects in therapy for acute coronary syndromes: the case of abciximab in high-risk patients undergoing percutaneous transluminal coronary angioplasty in the EPIC study

    Eur Heart J

    (1998)
  • Cited by (636)

    • Search for Holy Grail of Stent Coating Will Go On

      2022, Cardiovascular Revascularization Medicine
    View all citing articles on Scopus
    View full text