Prediction of bare metal stent restenosis

Abstract

Methods for predicting whether or not a patient is likely to experience restenosis after the placement of a bare metal stent are provided. The methods involve detecting and analyzing gene expression patterns of the cellular components of whole blood, where activation of selected genes has been found to be indicative of a high probability of restenosis. The method thus allows the identification, prior to placement of a stent, of patients who are i) likely to experience restenosis, and thus should receive a stent that includes anti-restenosis agents; or ii) unlikely to experience restenosis, and thus should receive a stent without anti-stenosis agents.

Description

FIELD OF THE INVENTION[0001]The invention generally relates to predicting the probability of restenosis in patients receiving bare metal stents in native coronary arteries. In the preferred embodiment, the invention provides methods for predicting whether or not a patient is likely to experience restenosis based on the analysis of gene expression profiles of mRNA-containing components of whole blood, and, based on this prediction, determining whether the patient should receive a bare metal stent or a stent containing anti-restenosis agents.BACKGROUND OF THE INVENTION[0002]Coronary artery disease is the most prevalent medical problem in the industrialized world. It accounts for over 40% of all deaths in the United States and Western Europe (1). A primary therapy for coronary artery disease is coronary angioplasty with stent implantation (2).[0003]Until recently the success of coronary stenting was limited by the process of restenosis, which occurred in 20-40% of cases (3). There have...

AI Technical Summary

Benefits of technology

[0009]The invention provides a method of predicting the probability of occurrence of restenosis following placement of a bare metal stent in a native coronary artery of a patient, and methods to predict whether any given patient should receive a bare metal stent or a stent that contains anti-restenosis agents. The invention is based on a heretofore unknown association between overall increased gene activation / up-regulation in the mRNA-containing compartment of whole blood and the likelihood of restenosis. According to the invention, gene expression profiles of the RNA containing compartment of whole blood are used to detect gene activation, and this information is correlated with a probability of the occurrence of restenosis. The ability to predict which patients are at risk for or predisposed to restenosis and which patients are not permits the selective choice of stent type, i.e. bare metal stent vs drug eluting stent: patients with a low risk (less than or equal to a probability output of 50% as determined herein) can receive bare metal stents, thereby decreasing costs and the risk of major adverse clinical events attributable to use of drug eluting stents and the necessary use of long term anti-platelet agents, whereas patients with a high risk (probability output greater than 50% as determined herein) can receive stents that include anti-restenosis agents.

Problems solved by technology

Until recently the success of coronary stenting was limited by the process of restenosis, which occurred in 20-40% of cases (3).

The clinical and lesion related risk factors for restenosis, however, are very poorly predictive of restenosis.

Bare metal stents are utilized much less frequently compared to drug eluting stents because restenosis is a known problem associated with using bare metal stents.

Using a drug-coated stent instead of a bare metal stent is associated with excess costs.

This may occur at an annual rate of 0.2-0.6% and may result in significant excess morbidity and mortality (11).

Despite the length of time that restenosis has been an issue and has been the subject of research no current technology exists for reliably determining whether an individual patient is likely to experience restenosis if given a bare metal stent rather than a drug coated stent, i.e., whether the drug coated stent is truly required to prevent restenosis.

In addition to the excess costs associated with drug eluting stents, other associated clinical problems may be introduced by indiscriminately using drug coated stents for some patients who might have similar outcomes with a bare metal stent.

These include an excess risk of bleeding associated with the need for long term anti-platelet agents in those individuals receiving drug elution stents and the risk of sub-acute stent thrombosis, a particularly severe adverse event associated with 40% mortality rate, in those individuals who may be non-compliant with the prescribed regimen or required to stop anti-platelet agents for other non-related surgical procedures.

The prior art has thus far failed to provide a reliable method for assessing the risk of restenosis in individual patients slated for stent placement.

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