The MOVEMENT Trial

Manne Holm, Per Tornvall, Loghman Henareh, Ulf Jensen, Nanna Golster, Patrik Alström, Irene Santos-Pardo, Nils Witt, Nikolai Fedchenko, Dimitrios Venetsanos, Olof Beck, Jan van der Linden, Manne Holm, Per Tornvall, Loghman Henareh, Ulf Jensen, Nanna Golster, Patrik Alström, Irene Santos-Pardo, Nils Witt, Nikolai Fedchenko, Dimitrios Venetsanos, Olof Beck, Jan van der Linden

Abstract

Background Morphine administration is a strong predictor of delayed onset of action of orally administered ticagrelor in patients with ST-segment-elevation myocardial infarction, likely because of impaired gastrointestinal motility. The aim of this study was to evaluate whether the peripheral opioid antagonist methylnaltrexone could improve pharmacodynamics and pharmacokinetics of orally administered ticagrelor in patients with ST-segment-elevation myocardial infarction receiving morphine. Methods and Results The MOVEMENT (Methylnaltrexone to Improve Platelet Inhibition of Ticagrelor in Morphine-Treated Patients With ST-Segment Elevation Myocardial Infarction) trial was a multicenter, prospective, randomized, controlled trial in patients with ST-segment-elevation myocardial infarction treated with morphine and ticagrelor. Upon arrival to the catheterization laboratory, patients were randomized to a blinded intravenous injection of either methylnaltrexone (8 or 12 mg according to weight) or 0.9% sodium chloride. The proportion of patients with high on-treatment platelet reactivity and plasma concentrations of ticagrelor and AR -C124910XX were assessed at baseline (arrival in the catheterization laboratory) and 1 and 2 hours later. A total of 82 patients received either methylnaltrexone (n=43) or placebo (n=39). Median (interquartile range) time from ticagrelor administration to randomization was 41 (31-50) versus 45.5 (37-60) minutes ( P=0.16). Intravenous methylnaltrexone administration did not significantly affect prevalence of high on-treatment platelet reactivity at 2 hours after inclusion, the primary end point, when compared with placebo (54% versus 51%, P=0.84). Plasma concentrations of ticagrelor and its active metabolite, the prespecified secondary end points, did not differ significantly between the groups over time. There was no significant difference in patient self-estimated pain between the groups. Conclusions Methylnaltrexone did not significantly improve platelet reactivity or plasma concentrations of orally administered ticagrelor in patients with ST-segment-elevation myocardial infarction receiving morphine. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02942550.

Trial registration: ClinicalTrials.gov NCT02942550.

Keywords: ST‐segment–elevation myocardial infarction; angioplasty and stenting; antiplatelet therapy; myocardial infarction; narcotic antagonists; opioid; pharmacodynamics; pharmacokinetics; purinergic P2Y receptor antagonists.

Figures

Figure 1
Figure 1
Enrollment and randomization. Patients who presented with ST‐segment–elevation myocardial infarction (STEMI) at the respective cardiac catheterization laboratories were considered for study inclusion. The figure shows the number of patients enrolled in the study and randomized. LD indicates Loading Dose; MOVEMENT, Methylnaltrexone to Improve Platelet Inhibition of Ticagrelor in Morphine‐Treated Patients With ST‐Segment–Elevation Myocardial Infarction; PCI, percutaneous coronary intervention.
Figure 2
Figure 2
Prevalence of high on‐treatment platelet reactivity (HPR). Defined as ≥50% platelet reactivity index with the vasodilator‐associated stimulated phosphoprotein assay before inclusion and 1  and 2 hours after study intervention. Differences in the prevalence in HPR were tested with chi‐square test.

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