Effect of prasugrel in patients with asthma: results of PRINA, a randomized, double‐blind, placebo‐controlled, cross‐over study. (16th December 2014)

• Record Type: Journal Article
• Authors: Lussana, F.; Di Marco, F.; Terraneo, S.; Parati, M.; Razzari, C.; Scavone, M.; Femia, E. A.; Moro, A.; Centanni, S.; Cattaneo, M.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 13:Number 1(2015:Jan.)
• Page Start: 136
• Page End: 141
• Publication Date: 2014-12-16
• Subjects: Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.12779
• Languages: English
• ISSNs: 1538-7933

Abstract

<abstract abstract-type="main" id="jth12779-abs-0001"> <title>Summary</title> <sec id="jth12779-sec-0001" sec-type="section"> <title>Background</title> <p>Although experimental studies have demonstrated that platelets are proinflammatory cells, no randomized studies have tested the anti‐inflammatory effect of antiplatelet agents in humans. The platelet P2Y<sub>12</sub> receptors mediated bronchial inflammation in a mouse model of asthma, suggesting that P2Y<sub>12</sub> represents a pharmacologic target for asthma.</p> </sec> <sec id="jth12779-sec-0002" sec-type="section"> <title>Objectives</title> <p>In this proof‐of concept, placebo‐controlled, randomized, cross‐over study, we tested the effects of the P2Y<sub>12</sub> antagonist prasugrel on bronchial hyperreactivity of asthmatic patients.</p> </sec> <sec id="jth12779-sec-0003" sec-type="section"> <title>Patients/Methods</title> <p>Twenty‐six asthmatic patients were randomly and blindly allocated to prasugrel (10 mg once daily) or placebo for 15 days. After a ≥ 15‐day wash‐out, patients were crossed over to the alternative treatment. Before and after each treatment, patients underwent a bronchial provocation test with mannitol and measurement of fractional exhaled nitric oxide (FeNO). Inhibition of P2Y<sub>12</sub>‐dependent platelet reactivity (platelet reactivity index [PRI]) was measured with the vasodilator‐stimulated phosphoprotein phosphorylation assay.</p> </sec> <sec id="jth12779-sec-0004" sec-type="section"> <title>Results</title> <p>The provocative dose of mannitol causing a 15% drop in forced expiratory volume in 1 s increased from 142 mg (95% confidence interval [CI] 82–202) to 187 mg (95% CI 113–262) after prasugrel treatment (<italic>P</italic> = 0.09), and did not change after placebo treatment (136 mg [95% CI 76–196] and 144 mg [95% CI 84–204], <italic>P</italic> = 0.65). FeNO did not change after either treatment. The PRI decreased from 80% (95% CI 77–83) to 23% (95% CI 7–29) after prasugrel treatment (<italic>P</italic> < 0.001) and remained unchanged after placebo.</p> </sec> <sec id="jth12779-sec-0005" sec-type="section"> <title>Conclusions</title> <p>Our proof‐of‐concept, randomized, controlled study is the first one to test <italic>in vivo</italic> the anti‐inflammatory effects of platelet inhibition in human patients. The results suggest that pharmacologic inhibition of P2Y<sub>12</sub> receptors may slightly reduce the bronchial inflammatory burden, and lay the groundwork for further studies, with clinical endpoints.</p> </sec> </abstract>