NCX-4016 is a nitric oxide-releasing derivative of aspirin with antiplatelet activity.
In this study, researchers from Italy and France investigated the effect of NCX-4016 on gastrointestinal mucosa and platelet function in healthy human volunteers.
They performed a parallel-group, double-blind, placebo-controlled study.
The research team randomized 40 healthy subjects to receive 7 days of treatment with NCX-4016 (400 and 800 mg twice daily), aspirin (200 and 420 mg twice daily), or placebo.
They performed upper endoscopies were performed before and after the treatment period.
|NCX-4016 was found to be virtually devoid of gastric and duodenal toxicity.|
Gastroduodenal lesions were graded using a predefined scoring system.
The team investigated basal and post-treatment platelet aggregation in response to arachidonic acid (AA), serum thromboxane (TX) B2, and AA-stimulated platelet TXB2.
The research team found that the mucosal endoscopic injury score on day 7 was 0.63 in the placebo group, and 11 and 16.1 in the 200 and 420 mg aspirin groups, respectively.
NCX-4016 was found to be virtually devoid of gastric and duodenal toxicity, resulting in a total gastric and duodenal endoscopic score of 1.38 and 1.25.
In addition, NCX-4016 inhibited AA-induced platelet aggregation, as well as serum TXB2 and platelet TXB2 generation induced by AA, to the same extent as aspirin.
Dr Stefano Fiorucci's team concluded, "Addition of an NO-donating moiety to aspirin results in a new chemical entity that maintains cyclooxygenase-1 and platelet inhibitory activity while nearly avoiding gastrointestinal damage".
In a related editorial in the same publication, Prof. David Peura, from the University of Virginia Health Sciences Center, USA, discusses the use of aspirin in cardiovascular disease.
He states that "Americans consume 29 billion tablets each year, of which almost 40% is for cardioprotection"
However, "Aspirin causes gastric and duodenal ulcers and, even at doses as low as 75 mg per day, substantially increases the risk of gastrointestinal bleeding".
"Altering its formulation by buffering or enteric coating does not seem to modify this risk of bleeding."
Prof. Peura also discusses Fiorucci et al's study - a first step toward producing safer aspirin.
He concludes, however, "Answers that are necessary before NO-aspirin can be recommended for general clinical use."