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The effect of desmopressin on bleeding time and platelet aggregation in healthy volunteers administered ticagrelor.

Abstract：

WHAT IS KNOWN AND OBJECTIVE:Ticagrelor is a reversibly binding and selective P2Y12 -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. METHODS: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 μg/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. RESULTS: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. WHAT IS NEW AND CONCLUSION: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.

journal_name

J Clin Pharm Ther

journal_title

Journal of clinical pharmacy and therapeutics

authors

Teng R,Mitchell PD,Butler K

doi

10.1111/jcpt.12130

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

186-91

issue

eissn

0269-4727

issn

1365-2710

journal_volume

pub_type

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The effect of desmopressin on bleeding time and platelet aggregation in healthy volunteers administered ticagrelor.