Editorial
Nitric oxide-releasing aspirin: Will it say NO to atherothrombosis?☆

https://doi.org/10.1016/j.ijcard.2006.08.002Get rights and content

Abstract

Aspirin is a powerful anti-platelet drug widely used in patients with coronary atherosclerosis, but its side effects and especially its toxicity for gastrointestinal tract limit its usefulness in specific groups of patients. A new category of agents, nitric oxide-releasing aspirins (such as NCX-4016), seems to provide an alternative solution. Although this drug is still at phase II clinical trials, it has provided promising results until now. When administered in vivo, it is separated into an aspirin moiety and an NO-donating complex, providing both the antithrombotic effect of aspirin and the gastroprotective effect of NO. Additionally, it increases NO bioavailability as a vascular level, and it may have the antiatherogenic properties of endogenously produced NO. Finally, recent evidence suggests that it may also improve functional aspects of vein grafts used in CABG, with possible benefit on graft patency. However, the outcome of the large ongoing trials is needed before any conclusion is made about the role of NO-releasing aspirins in cardiovascular disease.

Introduction

In this issue of the journal, Lorusso et al. presented an elegant study [1], demonstrating an important aspect of the effect of nitric oxide-releasing aspirin (NCX-4016) on human vasculature: its vasodilatory effect on venous grafts used for coronary artery bypass grafting operation (CABG). It seems that NCX-4016 has significant vasodilatory properties by acting directly on vein grafts, an effect which is not modified by the well demonstrated functional abnormalities of vascular wall, observed in diabetes mellitus.

Despite its complicated chemical name, NCX-4016 is designed based on a simple but brilliant idea: to combine in a single molecule, the most widely used agent in cardiovascular disease, aspirin, and a donor of probably the most important signaling molecule in human vessels, nitric oxide (NO).

Section snippets

Aspirin: an old drug with great benefits in cardiovascular disease

Acetylosalicylic acid, or aspirin, was discovered during the 19th century [2], and despite its toxic effects on gastrointestinal tract [3] it became a first line agent against cardiovascular death, by preventing thrombotic events [4] and atherothrombosis in general [5], further to its well-known anti-inflammatory properties [2]. It is really interesting that the antithrombotic effect of aspirin is not due to salicylate but it is caused by the acetyl group on its molecule, which inhibits

Aspirin: any improvements to minimize side effects?

A promising alternative solution to minimize the side effects of aspirin on gastric mucosa without compromising its antithrombotic efficacy is a newly designed category of antithrombotic agents, the NO-releasing aspirin. Based on evidence that NO protects gastric mucosa by reducing microvascular ischemia [9], the NO-releasing aspirins may provide the solution to this problem.

NO-releasing aspirin NCX-4016: all in one molecule

NCX-4016 molecule is actually consisted of an aspirin group, a spacer joint by an ester linkage and an NO-releasing group [10]. When administered in vivo, esterases separate the aspirin moiety from the benzene spacer-NO complex, leading to the release of NO from this complex. The release of NO from NCX-4016 in vivo seems to be time- and concentration-dependent, since it possibly shares a common pathway with glycerol trinitrate, as implied by the presence of bidirectional cross-tolerance at the

References (21)

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☆

Invited Editorial on article entitled: “Functional effects of nitric oxide-releasing aspirin on vein conduits of diabetic patients undergoing CABG” by Lorusso et al., Published in the current issue of IJC.

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