The effect of desmopressin on bleeding time and platelet aggregation in healthy volunteers administered ticagrelor. (21st January 2014)

• Record Type: Journal Article
• Authors: Teng, R.; Mitchell, P. D.; Butler, K.
• Is Part Of: Journal of clinical pharmacy and therapeutics. Volume 39:Number 2(2014:Apr.)
• Page Start: 186
• Page End: 191
• Publication Date: 2014-01-21
• Subjects: Clinical pharmacology -- Periodicals; Chemotherapy -- Periodicals; 615
• DOI: 10.1111/jcpt.12130
• Languages: English
• ISSNs: 0269-4727

Abstract

<abstract abstract-type="main" id="jcpt12130-abs-0001"> <title>Summary</title> <sec id="jcpt12130-sec-0001" sec-type="section"> <title>What is known and objective</title> <p>Ticagrelor is a reversibly binding and selective P2Y<sub>12</sub>‐receptor antagonist approved for the prevention of atherothrombotic events in patients with acute coronary syndromes. As bleeding events remain a hazard with antiplatelet therapy, this study investigated the effect of the vasopressin agonist, desmopressin, on ticagrelor‐induced bleeding time prolongation. Desmopressin has previously been shown to improve primary haemostasis and is widely used as first‐line therapy for individuals with bleeding disorders.</p> </sec> <sec id="jcpt12130-sec-0002" sec-type="section"> <title>Methods</title> <p>In a randomized, double‐blind, 2‐period crossover study, healthy volunteers received ticagrelor (270 mg loading dose; 180 mg bid) for 5 days. On Day 5, desmopressin (0·3 <italic>μ</italic>g/kg) or saline intravenous infusions were administered. The impact of desmopressin on bleeding time, inhibition of platelet aggregation (IPA), platelet function and ticagrelor pharmacokinetic parameters was investigated.</p> </sec> <sec id="jcpt12130-sec-0003" sec-type="section"> <title>Results</title> <p>Twenty‐one volunteers (81% male) were enrolled. Median [range] bleeding times were slightly reduced with ticagrelor plus desmopressin compared with ticagrelor alone (7·50 [3–17] vs. 10·50 [3–25] min at 2·5 h). Median reductions in bleeding time from baseline were generally similar between ticagrelor plus desmopressin compared with ticagrelor alone at all time points. Co‐administration of desmopressin had no impact on IPA, although platelet reactivity was significantly increased (von Willebrand Factor antigen: GLS mean AUEC was 4667%.h for ticagrelor plus desmopressin compared with 2750%.h for ticagrelor alone). Desmopressin did not influence the pharmacokinetics of ticagrelor.</p> </sec> <sec id="jcpt12130-sec-0004" sec-type="section"> <title>What is new and conclusion</title> <p>Desmopressin had no significant effect on bleeding time or inhibition of platelet aggregation by ticagrelor, although primary haemostatic activity was significantly increased. Ticagrelor pharmacokinetic parameters were not affected by co‐administration with desmopressin. Therefore, desmopressin is unlikely to be an effective therapeutic agent for control of the potential bleeding events associated with ticagrelor.</p> </sec> </abstract>