title: Effect of Modifying Antiplatelet Treatment to Ticagrelor in High-Risk Coronary Patients With Low Response to Clopidogrel (MATTIS).
abstract: Treatment with clopidogrel is subject to wide variability in response, and high on-treatment platelet reactivity (HTPR) is associated with increased risk of ischemic events. Ticagrelor has been shown to have antiplatelet effects superior to those of clopidogrel, with subsequent reduced clinical ischemic events. However, the efficacy of ticagrelor in high-risk patients with coronary disease who have high on-treatment platelet reactivity (HTPR) with clopidogrel has not been examined.
  
  
  
  We recruited 201 patients (mean age, 64 ± 10 years; 20% women) with stable/unstable angina who were receiving clopidogrel treatment and in whom coronary catheterization was planned. Platelet reactivity was tested using VerifyNow P2Y12 assay (Accumetrics, San Diego, CA) (HTPR defined as P2Y12 reaction units [PRU] ≥ 208). Patients with HTPR were randomized to receive either additional clopidogrel 300 mg or ticagrelor 180 mg before coronary angiography, and persisted with the respective treatment after percutaneous coronary intervention (PCI). The primary end point was the rate of troponin elevation after PCI, and the secondary end point was the change in platelet reactivity 24 hours after PCI. In addition, clinical outcomes at 30 days were evaluated.
  
  
  
  Eighty-four (42%) patients had HTPR (mean PRU, 270.8 ± 46.5) and were randomly assigned to clopidogrel or ticagrelor treatment. Subsequently, 49 patients underwent percutaneous coronary intervention (PCI) (26 receiving ticagrelor and 23 receiving clopidogrel). After PCI, the mean PRU in the ticagrelor group declined significantly (ticagrelor, 59.3 ± 49 vs clopidogrel, 202.4 ± 60.4; P < 0.0001). The rate of cardiac troponin elevation and clinical ischemic events were similar between the groups.
  
  
  
  In high-risk patients with coronary disease and HTPR on clopidogrel, ticagrelor was highly effective in platelet inhibition and overcoming HTPR compared with continued clopidogrel treatment but had no apparent effect on troponin release or short-term clinical outcomes.
authors.affiliation: Department of Cardiology, Rambam Medical Center and Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Anees
authors.initials: A
authors.lastname: Musallam
authors.affiliation: Cardiology Department, Rabin Medical Center, Petah Tikva, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Katia
authors.initials: K
authors.lastname: Orvin
authors.affiliation: Cardiology Department, Rabin Medical Center, Petah Tikva, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Leor
authors.initials: L
authors.lastname: Perl
authors.affiliation: Cardiology Division, Meir Medical Center, Kfar Saba, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Morris
authors.initials: M
authors.lastname: Mosseri
authors.affiliation: Cardiology Division, Meir Medical Center, Kfar Saba, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yoel
authors.initials: Y
authors.lastname: Arbel
authors.affiliation: Department of Cardiology, Rambam Medical Center and Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Roguin
authors.affiliation: Cardiology Department, Rabin Medical Center, Petah Tikva, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: elil@clalit.org.il.
authors.forename: Eli I
authors.initials: EI
authors.lastname: Lev
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014336:Troponin / Q000097:blood*
chemical_list: D010975:Platelet Aggregation Inhibitors; D014336:Troponin; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine