Platelet glycoprotein Illa polymorphisms and risk of coronary stent thrombosis

doi:10.1016/S0140-6736(97)05399-3

The Lancet

Volume 350, Issue 9086, 25 October 1997, Pages 1217-1219

https://doi.org/10.1016/S0140-6736(97)05399-3 Get rights and content

Summary

Background

Coronary stents are an effective treatment for selected coronary stenoses. However, thrombosis of the stented segment is a major adverse complication. Platelet aggregation has a key role in stent thrombosis. We investigated whether a polymorphism of platelet glycoprotein Illa gene (Pl^A2) is associated with an increased risk of coronary stent thrombosis.

Methods

318 consecutive patients were followed up for 30 days after coronary stent insertion. The primary endpoints were death, myocardial infarction, stent-vessel occlusion, and coronary artery bypass surgery. Gel electrophoresis of PCR products was used to identify the Pl^A1 and Pl^A2 alleles. The relative risk of stent occlusion was calculated from the odds ratio on logistic regression analysis.

Findings

63 (19·8%) of patients had the Pl^A2 allele and 255 (80·2%) were homozygous for Pl^A1. Baseline clinical, angiographic, and procedural features did not differ between the groups with and without the Pl^A2 allele. Occlusion of the stent vessel occurred in five (1·9%) patients homozygous for Pl^A1 and six (9·5%) patients with Pl^A2 allele (odds ratio 5·26 [95% Cl 1·55–17·85]). On multivariate regression analysis Pl^A1/A2 genotype was the only significant independent predictor of stent thrombosis.

Interpretation

Patients with the Pl^A2 allele have an increased risk of coronary stent thrombosis, which may warrant antiplatelet therapy with glycoprotein-llb/Illa inhibitors, although bleeding complications may also increase.

Introduction

Coronary stents are a valuable non-surgical technique in the management of failed angioplasty or to prevent restenosis in selected coronary artery lesions.1, 2, 3, 4 However, occlusion of the stent vessel caused by acute or subacute thrombosis is a devastating complication frequently associated with adverse clinical events.5, 6 Other studies have shown the pivotal role of platelet activation and aggregation in the production of coronary stent thrombosis.7, 8, 9, 10

The final common pathway to platelet aggregation involves binding of fibrinogen to the glycoprotein IIb/IIIa receptor on the platelet surface.¹¹ Inhibition of the glycoprotein IIb/IIIa receptor decreases the risk of acute thrombotic complications after coronary angioplasty in high-risk patients.¹² The strong association between a polymorphism of the glycoprotein IIIa gene (Pl^A2) and acute coronary syndromes¹³ suggests that the Pl^A2 phenotype has a functional role in thrombotic complications of coronary artery disease. Therefore, we carried out a prospective study on the association between the Pl^A2 allele and coronary stent thrombosis.

Section snippets

Methods

The study included 318 consecutive patients with coronary stents implanted between January, 1996, and March, 1997. The indications for stenting were: coronary dissection, acute occlusion (Thrombolysis in Myocardial Infarction [TIMI] flow of 0 or 1), or suboptimal results (⩾30% residual stenosis) after percutaneous transluminal coronary angioplasty, lesions in venous bypass-grafts, and restenotic lesions. All patients with a stent successfully inserted in the target lesion were included in the

Results

63 (19·8%) of the 318 patients had the Pl^A2 allele and 255 (80·2%) patients were homozygous for Pl^A1. No patient was homozygous for Pl^A2. Similar allelic frequencies of Pl^A1 and Pl^A2 have been reported previously in a European population.¹⁷ Baseline clinical characteristics (table 1) and angiographic and procedural variables (data not shown) did not differ between patients with and without the Pl^A2 allele. Patients with the Pl^A2 allele had a significantly higher frequency of stent-vessel

Discussion

We found a strong association between Pl^A2, a polymorphism of the glycoportein IIIa gene, and coronary stent thrombosis.

The frequency of coronary stent thrombosis in all study patients was 3·4%, which is slightly higher than that found in large trials with similar aggressive antiplatelet regimens.8, 10 However, more than 50% of our patients had an acute coronary syndrome at enrolment, and the risk of thrombosis is higher in this setting. More severe lesions and more extensive disease in our

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Early ReportPlatelet glycoprotein Illa polymorphisms and risk of coronary stent thrombosis

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Methods

Results

Discussion

A comparison of coronary-artery stenting with angioplasty for isolated stenosis of the proximal left anterior descending coronary artery

N Engl J Med

Multicenter investigation of coronary stenting to treat acute or threatened closure after percutaneous transluminal coronary angioplasty: clinical and angiographic outcomes

J Am Coll Cardiol

A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease

N Engl J Med

A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease

N Engl J Med

Results of a consecutive series of patients receiving only antiplatelet therapy after optimized stent implantation

Circulation

Stent thrombosis

Circulation

Prospective evaluation of hemostatic predictors of subacute stent thrombosis after coronary Palmaz-Schatz stenting

J Am Coil Cardiol

A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents

N Engl J Med

Intracoronary stenting without anticoagulation accomplished with intravascular ultrasound guidance

Circulation

Intracoronary stent implantation without ultrasound guidance and with replacement of conventional anticoagulation by antiplatelet therapy

Circulation

Cellular adhesion: GPIIb/IIa as a prototypic adhesion receptor

Early Report
Platelet glycoprotein Illa polymorphisms and risk of coronary stent thrombosis