Importance: Dual anti-platelet therapy represents standard care for treating patients with ST-segment elevation myocardial infarction (STEMI). Ticagrelor is a direct-acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation. Objective: To evaluate whether chewing a loading dose (LD) of ticagrelor, 180 mg, vs traditional oral administration of an equal dose enhances platelet inhibition at 30 minutes and 1 hour after LD administration in patients with STEMI. Design, Setting, and Participants: A randomized clinical trial was conducted in adults aged 30 to 87 years from May to October 2016 in a large tertiary care center. Analyses were intention-to-treat. Interventions: Fifty patients with STEMI were randomized to either chewing an LD of ticagrelor, 180 mg, or standard oral administration of an equal dose. Main Outcomes and Measures: P2Y12 reaction units were evaluated using VerifyNow (Accumentrics) at baseline, 30 minutes, 1 hour, and 4 hours after LD. Results: Baseline characteristics were similar in both groups. The mean (SD) of P2Y12 reaction units in the chewing group compared with the standard group at baseline, 30 minutes, 1 hour, and 4 hours after ticagrelor LD were 224 (33) vs 219 (44) (95% CI, -16.77 to 27.73; P = .26), 168 (78) vs 230 (69) (95% CI, -103.77 to -19.75; P = .003), 106 (90) vs 181 (89) (95% CI, -125.15 to -26.29; P = .005), and 43 (41) vs 51 (61) (95% CI, -36.34 to 21.14; P = .30), respectively. Platelet reactivity in the chewing group was significantly reduced by 24% at 30 minutes after LD (95% CI, 19.75 to 103.77; P = .001). The relative inhibition of platelet aggregation in the chewing vs the standard group were 51% vs 10% (95% CI, 13.69 to 67.67; P = .005) at 1 hour and 81% vs 76% (95% CI, -12.32 to 16.79; P = .24) at 4 hours, respectively. Major adverse cardiac and cardiovascular event rate at 30 days was low (4%) and occurred in 1 patient in each group (95% CI, 0.06 to 16.93; P > .99). Conclusions and Relevance: Chewing an LD of ticagrelor, 180 mg, in patients with STEMI is feasible and facilitates better early platelet inhibition compared with a standard oral LD. Larger studies are warranted to see if our preliminary findings translate into clinical outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT02725099.
RCT Entities:
Importance: Dual anti-platelet therapy represents standard care for treating patients with ST-segment elevation myocardial infarction (STEMI). Ticagrelor is a direct-acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation. Objective: To evaluate whether chewing a loading dose (LD) of ticagrelor, 180 mg, vs traditional oral administration of an equal dose enhances platelet inhibition at 30 minutes and 1 hour after LD administration in patients with STEMI. Design, Setting, and Participants: A randomized clinical trial was conducted in adults aged 30 to 87 years from May to October 2016 in a large tertiary care center. Analyses were intention-to-treat. Interventions: Fifty patients with STEMI were randomized to either chewing an LD of ticagrelor, 180 mg, or standard oral administration of an equal dose. Main Outcomes and Measures: P2Y12 reaction units were evaluated using VerifyNow (Accumentrics) at baseline, 30 minutes, 1 hour, and 4 hours after LD. Results: Baseline characteristics were similar in both groups. The mean (SD) of P2Y12 reaction units in the chewing group compared with the standard group at baseline, 30 minutes, 1 hour, and 4 hours after ticagrelor LD were 224 (33) vs 219 (44) (95% CI, -16.77 to 27.73; P = .26), 168 (78) vs 230 (69) (95% CI, -103.77 to -19.75; P = .003), 106 (90) vs 181 (89) (95% CI, -125.15 to -26.29; P = .005), and 43 (41) vs 51 (61) (95% CI, -36.34 to 21.14; P = .30), respectively. Platelet reactivity in the chewing group was significantly reduced by 24% at 30 minutes after LD (95% CI, 19.75 to 103.77; P = .001). The relative inhibition of platelet aggregation in the chewing vs the standard group were 51% vs 10% (95% CI, 13.69 to 67.67; P = .005) at 1 hour and 81% vs 76% (95% CI, -12.32 to 16.79; P = .24) at 4 hours, respectively. Major adverse cardiac and cardiovascular event rate at 30 days was low (4%) and occurred in 1 patient in each group (95% CI, 0.06 to 16.93; P > .99). Conclusions and Relevance: Chewing an LD of ticagrelor, 180 mg, in patients with STEMI is feasible and facilitates better early platelet inhibition compared with a standard oral LD. Larger studies are warranted to see if our preliminary findings translate into clinical outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT02725099.
Authors: Deepak L Bhatt; Gregg W Stone; Kenneth W Mahaffey; C Michael Gibson; P Gabriel Steg; Christian W Hamm; Matthew J Price; Sergio Leonardi; Dianne Gallup; Ezio Bramucci; Peter W Radke; Petr Widimský; Frantisek Tousek; Jeffrey Tauth; Douglas Spriggs; Brent T McLaurin; Dominick J Angiolillo; Philippe Généreux; Tiepu Liu; Jayne Prats; Meredith Todd; Simona Skerjanec; Harvey D White; Robert A Harrington Journal: N Engl J Med Date: 2013-03-10 Impact factor: 91.245
Authors: Matthew J Price; Dominick J Angiolillo; Paul S Teirstein; Elizabeth Lillie; Steven V Manoukian; Peter B Berger; Jean-François Tanguay; Christopher P Cannon; Eric J Topol Journal: Circulation Date: 2011-08-29 Impact factor: 29.690
Authors: Eugene Braunwald; Dominick Angiolillo; Eric Bates; Peter B Berger; Deepak Bhatt; Christopher P Cannon; Mark I Furman; Paul Gurbel; Alan D Michelson; Eric Peterson; Stephen Wiviott Journal: Clin Cardiol Date: 2008-03 Impact factor: 2.882
Authors: Francesco Franchi; Fabiana Rollini; Jung Rae Cho; Mona Bhatti; Christopher DeGroat; Elisabetta Ferrante; Elizabeth C Dunn; Amit Nanavati; Edward Carraway; Siva Suryadevara; Martin M Zenni; Luis A Guzman; Theodore A Bass; Dominick J Angiolillo Journal: JACC Cardiovasc Interv Date: 2015-09 Impact factor: 11.195
Authors: Giuseppe Gargiulo; Giovanni Esposito; Plinio Cirillo; Michael Nagler; Pietro Minuz; Gianluca Campo; Felice Gragnano; Negar Manavifar; Raffaele Piccolo; Marisa Avvedimento; Matteo Tebaldi; Andreas Wahl; Lukas Hunziker; Michael Billinger; Dik Heg; Stephan Windecker; Marco Valgimigli Journal: J Cardiovasc Transl Res Date: 2020-02-24 Impact factor: 4.132
Authors: Piotr Adamski; Katarzyna Buszko; Joanna Sikora; Piotr Niezgoda; Tomasz Fabiszak; Małgorzata Ostrowska; Malwina Barańska; Aleksandra Karczmarska-Wódzka; Eliano Pio Navarese; Jacek Kubica Journal: Sci Rep Date: 2019-03-08 Impact factor: 4.379