Prasugrel or Ticagrelor in ST-Segment–Elevation Myocardial Infarction Patients With Diabetes Mellitus
2017; Lippincott Williams & Wilkins; Volume: 136; Issue: 6 Linguagem: Inglês
10.1161/circulationaha.117.028745
ISSN1524-4539
AutoresGennaro Sardella, Massimo Mancone, Rocco Edoardo Stio, Erika Cavallo, Angelo Di Roma, Riccardo Colantonio, Simone Calcagno,
Tópico(s)Acute Myocardial Infarction Research
ResumoHomeCirculationVol. 136, No. 6Prasugrel or Ticagrelor in ST-Segment–Elevation Myocardial Infarction Patients With Diabetes Mellitus Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBPrasugrel or Ticagrelor in ST-Segment–Elevation Myocardial Infarction Patients With Diabetes Mellitus Gennaro Sardella, MD, Massimo Mancone, MD, PhD, Rocco Edoardo Stio, MD, PhD, Erika Cavallo, MD, Angelo Di Roma, MD, Riccardo Colantonio, MD and Simone Calcagno, MD Gennaro SardellaGennaro Sardella From Department of Cardiovascular, Respiratory, Geriatric, Anesthesiologic and Nephrologic Sciences, Umberto I Hospital, Sapienza University of Rome, Italy. , Massimo ManconeMassimo Mancone From Department of Cardiovascular, Respiratory, Geriatric, Anesthesiologic and Nephrologic Sciences, Umberto I Hospital, Sapienza University of Rome, Italy. , Rocco Edoardo StioRocco Edoardo Stio From Department of Cardiovascular, Respiratory, Geriatric, Anesthesiologic and Nephrologic Sciences, Umberto I Hospital, Sapienza University of Rome, Italy. , Erika CavalloErika Cavallo From Department of Cardiovascular, Respiratory, Geriatric, Anesthesiologic and Nephrologic Sciences, Umberto I Hospital, Sapienza University of Rome, Italy. , Angelo Di RomaAngelo Di Roma From Department of Cardiovascular, Respiratory, Geriatric, Anesthesiologic and Nephrologic Sciences, Umberto I Hospital, Sapienza University of Rome, Italy. , Riccardo ColantonioRiccardo Colantonio From Department of Cardiovascular, Respiratory, Geriatric, Anesthesiologic and Nephrologic Sciences, Umberto I Hospital, Sapienza University of Rome, Italy. and Simone CalcagnoSimone Calcagno From Department of Cardiovascular, Respiratory, Geriatric, Anesthesiologic and Nephrologic Sciences, Umberto I Hospital, Sapienza University of Rome, Italy. Originally published8 Aug 2017https://doi.org/10.1161/CIRCULATIONAHA.117.028745Circulation. 2017;136:602–604Prasugrel or ticagrelor is recommended in patients with ST-segment–elevation myocardial infarction (STEMI). Patients with diabetes mellitus are characterized by enhanced platelet reactivity (PR) and a reduced response to oral antiplatelet agents.1The RESET 2D trial (Prasugrel vs Ticagrelor in ST-Elevation Myocardial Infarction Patients With Diabetes Mellitus) was a prospective, randomized, pharmacodynamic study evaluating platelet inhibition by loading dose (LD) of ticagrelor or prasugrel in P2Y12-naïve patients with diabetes mellitus presenting with STEMI. The local ethics committee approved the study (ClinicalTrials.gov NCT01531114).All consecutive patients with STEMI with diabetes mellitus undergoing primary percutaneous coronary intervention who were P2Y12 naïve were considered for PR assessment. Major exclusion criteria were bleeding diathesis, periprocedural glycoprotein IIb/IIIa receptor inhibitor use, morphine administration, previous ischemic/hemorrhagic stroke, and any contraindication to antiplatelet therapy. Eligible patients were randomized 1:1 to receive ticagrelor 180-mg LD or prasugrel 60-mg LD at the time of percutaneous coronary intervention. All patients received oral aspirin 325 mg and intravenous unfractionated heparin (70 U/kg). Platelet function testing was performed with VerifyNow (Accumetrics, San Diego, CA) at baseline and at 1, 2, 6, and 12 hours, and the results are reported in P2Y12 reaction units (PRUs). High PR was defined as PRUs >208. The primary end point was the difference in antiplatelet effect in terms of PR level after a LD of prasugrel versus ticagrelor in patients with diabetes mellitus sand STEMI at 2 hours after drug administration.Considering the absence of data on a direct comparison in patients with STEMI with diabetes mellitus, on the basis of the superiority principle and in line with previous studies,2 our primary analysis was to test for superiority of prasugrel compared with ticagrelor at 2 hours after LD administration in terms of lower PRU assessment. To yield 80% power at a 2-sided α level of 0.05 and considering a dropout of 5%, we needed 50 patients. A subanalysis stratified by baseline insulin use was prospectively planned. The values are expressed as mean±SD with 95% confidence interval (CI). A value of P<0.05 was considered statistically significant. All patients signed informed consent.Fifty consecutive patients with diabetes mellitus presenting with STEMI and undergoing primary percutaneous coronary intervention were included in our study (25 in each arm). The onset of symptoms to LD time was on average 5 hours 53 minutes. No differences were observed in baseline clinical and therapeutic characteristics between the 2 groups, with the same frequency of baseline insulin use (68% [17 patients] versus 60% [15 patients] in the ticagrelor and prasugrel group, respectively; P=0.55) and no difference in baseline PRU value (265.8±92.8 versus 271.3±71.0; P=0.81; 95% CI, −41.5 to 52.4). PR decreased at 1 hour in both treatment arms, with no difference in PRU levels (158.6±33.8 versus 166.4±45.4 in the ticagrelor and prasugrel group, respectively; P=0.49; 95% CI, −14.3 to 31.2). At 2 hours, ticagrelor showed a trend of lower PRU compared with prasugrel (65.5±58.2 versus 110.6±102.1, respectively; P=0.06; 95% CI, −2.2 to 92.4; Figure, A). After 6 and 12 hours, the PRU values were not different (6 hours: P=0.68, 95% CI, −40.1 to 27.1; 12 hours: P=0.54, 95% CI, −28.9 to 53.6). No patients were classified as having high PR, and all patients had a percentage of inhibition of platelet aggregation ≥20% with no significant differences after ticagrelor or prasugrel LD at any study time. A subanalysis restricted to those treated with insulin at baseline also demonstrated no difference in PRU levels after ticagrelor and prasugrel LD (baseline: 249.1±90.0 versus 266.8±68.7; 1 hour: 171.4±96.3 versus 178.6±89.6; 2 hours: 84.2±60.9 versus 139.3±111.2; 6 hours: 76.5±74.4 versus 43±49.5; 12 hours: 84.5±89.1 versus 65.8±62.8, respectively; Figure, B).Download figureDownload PowerPointFigure. Platelet reactivity unit (PRU; mean±SD) assessed overall in patients with diabetes mellitus and ST-segment–elevation myocardial infarction (A) and in those treated with insulin at baseline (B) after ticagrelor (17 pts) and prasugrel (15 pts) loading dose.In an STEMI population of patients with diabetes mellitus, we observed a rapid onset of action of both ticagrelor and prasugrel to decrease PR soon after LD administration with a superiority trend of ticagrelor at only the 2-hour time point. The onset of action and magnitude of effect for both drugs in the present study were similar to findings from a previous study including patients with diabetes with stable coronary disease,3 but the onset seems to be more rapid than in prior studies including patients with STEMI.4 This could be attributed to the use of morphine in previous studies, which was excluded in the present study, with its negative effect previously demonstrated on the effects of irreversible and reversible P2Y12 receptor inhibitors. The morphine–antiplatelet agent interaction is not a drug-specific phenomenon, but it is related to the inhibition of the muscular activity of the stomach and the intestines, which may lead to vomiting or delayed gastric emptying. We tested whole tablets, but recent data demonstrated a faster onset of antiplatelet effect after crushed administration,5 and this method of administration could be taken into consideration in this high-risk population. In our study, we did not observe a different timing of the onset of action between prasugrel and ticagrelor in patients with diabetes mellitus treated with insulin or not treated. The main limitation of the study is the focus on antiplatelet measures of efficacy with no ability to assess effects on clinical outcomes.Gennaro Sardella, MD*Massimo Mancone, MD, PhDRocco Edoardo Stio, MD, PhDErika Cavallo, MDAngelo Di Roma, MDRiccardo Colantonio, MDSimone Calcagno, MD*DisclosuresNone.Footnotes*Drs Sardella and Calcagno contributed equally.Circulation is available at http://circ.ahajournals.org.Correspondence to: Gennaro Sardella, MD, Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, Policlinico Umberto I, Sapienza University of Rome, Viale del Policlinico 155, 00186 Rome, Italy. E-mail [email protected]References1. 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An unresolved dilemma, Minerva Cardiology and Angiology, 10.23736/S2724-5683.20.05570-X, 69:5 Ray A, Najmi A, Khandelwal G, Jhaj R and Sadasivam B (2020) Prasugrel Versus Ticagrelor in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: a Systematic Review and Meta-analysis of Randomized Trials, Cardiovascular Drugs and Therapy, 10.1007/s10557-020-07056-z, 35:3, (561-574), Online publication date: 1-Jun-2021. Ndrepepa G, Kastrati A, Menichelli M, Neumann F, Wöhrle J, Bernlochner I, Richardt G, Witzenbichler B, Sibbing D, Gewalt S, Angiolillo D, Hamm C, Hapfelmeier A, Trenk D, Laugwitz K, Schunkert H, Schüpke S and Mayer K (2020) Ticagrelor or Prasugrel in Patients With Acute Coronary Syndromes and Diabetes Mellitus, JACC: Cardiovascular Interventions, 10.1016/j.jcin.2020.07.032, 13:19, (2238-2247), Online publication date: 1-Oct-2020. Severino P, D'Amato A, Netti L, Pucci M, Infusino F, Maestrini V, Mancone M and Fedele F (2019) Myocardial Ischemia and Diabetes Mellitus: Role of Oxidative Stress in the Connection between Cardiac Metabolism and Coronary Blood Flow, Journal of Diabetes Research, 10.1155/2019/9489826, 2019, (1-16), Online publication date: 4-Apr-2019. Li D, Li S, Zheng J, Tang H, Qiu Y, Xue N and Cao Y (2019) Analysis of ticagrelor's cardio-protective effects on patients with ST-segment elevation acute coronary syndrome accompanied with diabetes, Open Medicine, 10.1515/med-2019-0017, 14:1, (234-240), Online publication date: 20-Feb-2019., Online publication date: 1-Jan-2019. Danielak D, Karaźniewicz-Łada M and Główka F (2017) Ticagrelor in modern cardiology - an up-to-date review of most important aspects of ticagrelor pharmacotherapy, Expert Opinion on Pharmacotherapy, 10.1080/14656566.2017.1421634, 19:2, (103-112), Online publication date: 22-Jan-2018. Calcagno S, Infusino F, Salvi N, Taccheri T, Colantonio R, Bruno E, Birtolo L, Severino P, Lavalle C, Pucci M, Sardella G, Mancone M and Fedele F (2020) The Role of Ranolazine for the Treatment of Residual Angina beyond the Percutaneous Coronary Revascularization, Journal of Clinical Medicine, 10.3390/jcm9072110, 9:7, (2110) August 8, 2017Vol 136, Issue 6 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.117.028745PMID: 28784829 Originally publishedAugust 8, 2017 Keywordsplatelet antagonistsprasugrel hydrochloridemyocardial infarctionplatelet function testmorphine clorideticagrelorPDF download Advertisement SubjectsPercutaneous Coronary InterventionPharmacologyStent
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