Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial

• Published in: The Lancet (British edition) 2019-09, Vol.394 (10204), p.1169-1180
• Main Authors: Ray, Kausik K, Gupta, Dinesh, Blick, David, Izzo, Mark, Kosmicki, Douglas, Mohammed, Akber, Hazan, Lydie, Platt, Bruce, Meholick, Alan, Handel, Franklin, Rodriguez, Mara, Suresh, Damodhar, Pounds, Kevin, Debs-Perez, Giselle, Kizhakekuttu, Tinoy, Maron, David, Clavijo, Leonardo, Ledesma, Gilbert, Krolick, Merrill, Rewerska, Barbara, Lampart, Jacek, Szynal, Slawomir, Jesionowski, Pawel, Skwarna, Bartosz, Jankowski, Maciej, Korol, Marek, Shustov, Sergey, Khlevchuk, Tatiana, Khovaeva, Yaroslava, Khirmanov, Vladimir, He, Lanjie, Huang, Wenjun, Rusev, Nikolay, Tokmakova, Maria, Raev, Dimitar, Mihov, Atanas, Hahn, Joo-Yong, Eliaschewitz, Freddy, Ortiz, Costantino, Lai, Wen T, Abrahamovych, Orest, Montigny, Martine, O'Keefe, Dennis, Belle-Isle, Jasmin, Kelly, Allan, Wilderman, Igor, Turi, Tibor, Bakai, Judit, Marusincova, Ivana, Rihacek, Ivan, Carda, Jiri, Cermak, Ondrej, Toursarkissian, Nicole, Bott, Jochen, Simonis, Gregor, Behnke, Thomas, Tan, Michinao, Oono, Atsuyuki, Yamamoto, Fumi, Fujimoto, Noritaka, Sonoda, Masahiro, Carnero, Gabriela, Chacon, Carolina, Sernia, Virginia, Vilamajo, Oscar G, Estrada, José N, López, Víctor G, Cortada, Jorge B, González, Alfonso S, Guerrero, Diego B, Villablanca, Alex, Sandoval, Jorge, Leon, Lucio, Figueroa, Christian, Chag, Milan, Urban, Miroslav, Sivak, Vladimir, Ozer, Necla, Johnston, Nina, Erlinge, David, Sinnaeve, Peter, Guedes, Antoine, Janssens, Luc, Morbey, Claire, Hamilton, Andrew, Godoy, Armando, Guitton, Javier, Cottin, Yves, Bazari, Rasha, Chan, Michael, Turturo, Maurizio, Accini, Jose, Nyman, Kai, Tan, Edgar, Auer, Johann, Militaru, Constantin, Fox, Kim, Diaz, Rafael, Kovář, František, Dalby, Anthony J
• Format: Article
• Language: English
• Subjects: Acute coronary syndromes; Aged; Angioplasty; Antiplatelet therapy; Aspirin; Aspirin - therapeutic use; Bleeding; Cardiovascular disease; Cardiovascular Diseases - mortality; Cerebral infarction; Coronary Angiography; Coronary artery; Coronary Artery Bypass; Coronary artery disease; Coronary Artery Disease - complications; Coronary Artery Disease - drug therapy; Coronary Stenosis - diagnostic imaging; Coronary vessels; Death; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Disease control; Double-Blind Method; Drug Therapy, Combination; Female; Heart attacks; Heart diseases; Heart surgery; Hemorrhage; Hemorrhage - chemically induced; Human health and pathology; Humans; Hypoglycemic Agents - therapeutic use; Life Sciences; Male; Middle Aged; Mortality; Myocardial infarction; Myocardial Infarction - epidemiology; Patients; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors - therapeutic use; Population; Randomization; Risk; Secondary Prevention; Stenosis; Stents; Stroke; Stroke - epidemiology; Subgroups; Therapy; Ticagrelor - therapeutic use
• ISSN: 0140-6736; 1474-547X; 1474-547X
• DOI: 10.1016/S0140-6736(19)31887-2

Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, pinteraction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p