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Bicocca Open Archive
Background: 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. Methods: 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). Findings: 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<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, pinteraction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk. Funding: AstraZeneca.
Bhatt, D., Steg, P., Mehta, S., Leiter, L., Simon, T., Fox, K., et al. (2019). 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. THE LANCET, 394(10204), 1169-1180 [10.1016/S0140-6736(19)31887-2].
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
Bhatt D. L.
;Steg P. G.;Mehta S. R.;Leiter L. A.;Simon T.;Fox K.;Held C.;Andersson M.;Himmelmann A.;Ridderstrale W.;Chen J.;Song Y.;Diaz R.;Goto S.;James S. K.;Ray K. K.;Parkhomenko A. N.;Kosiborod M. N.;McGuire D. K.;Harrington R. A.;Santos V.;Jain A.;Lendel I.;Russo M.;Haught W. H.;Bouza M.;Gogia H.;Banerjee S.;Kichura G.;Kantaros L.;Padron F.;Passi R.;Stone J.;Pursley M.;D'Urso M.;Gardner T.;Bennett J.;Nour K.;Saini S.;Zhang W.;Kumbhani D.;Thomas D.;Angiolillo D.;Bertolet B.;Roman-Miranda A.;Black R.;Manshadi R.;Vaca C.;Blanco A.;Napoli M.;Brabham D.;Akyea-Djamson A.;Desai P.;Prasada S.;Khaira A.;Forgosh L.;Lieber I.;Umpierrez G.;Singal D.;Londono J.;Fraser N.;Ruiz J.;Vega D.;Rodriguez L.;Brown C.;Syed F.;Aggarwala G.;Eaves W.;Foster M.;Gupta D.;Avino D.;Asfour W.;Tonnessen G.;Zhao X. -Q.;Singh N.;Brockmyre A.;Lepor N.;Shammas N.;Blick D.;Hearne S.;Prodafikas J.;Carell E.;Izzo M.;Karim A.;Zakhary B.;Atieh M.;Leichter S.;Meadows C.;Hotchkiss D.;Abu-Fadel M.;Wiseman A.;Bander J.;Shah M.;Banerjee S.;Ganim R.;Sopko K.;Khan M.;Lloret R.;Weirick T.;Mehta R.;Thadani U.;Bhargava A.;Kosiborod M.;Moya J.;Staniloae C.;Guerra Y. D.;Chhabra A.;Kosmicki D.;Shaheen W.;Mohammed A.;Bitters J. 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S.;Banerjee S.;Sathe P.;Adhyapak S.;Nguyen T.;Pham V.;Do H.;Nguyen A.;Nguyen H.;Truong B.;Jamil-Copley S.;Lang C.;Pell A.;Zaman A.;Storey R.;Swanson N.;Smith S.;Sharman D.;Braganza D.;Hammond P.;Moriarty A.;Bain S.;Pye M.;Sharp A.;Blagden M.;Randeva H.;Myhill T.;Viswanathan G.;Keeling P.;Clifford P.;Saxena M.;Lyons K.;McMurray J.;Jaafar F.;Murphy C.;Cartwright S.;Abouglila K.;Antalik L.;Krajci P.;Urban M.;Fazekas F.;Pella D.;Koleny D.;Vykoukalova T.;Macek V.;Vinanska D.;Jamriskova L.;Such S.;Fulop P.;Farsky S.;Bugan V.;Strbova J.;Micko K.;Palka Jr J.;Sivak V.;Kristensen D.;Refsgaard J.;Holmvang L.;Dixen U.;Nielsen H.;Egstrup K.;Jensen L. 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A.;Ruda M.;Elamin O.;Kovar F.;Dalby A. J.;Bueno H.;Chiang C. -E.;Parkhomenko A.;Nguyen T. Q.;Leonsson-Zachrisson M.
2019
Abstract
Background: 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. Methods: 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). Findings: 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<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, pinteraction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk. Funding: AstraZeneca.
Bhatt, D., Steg, P., Mehta, S., Leiter, L., Simon, T., Fox, K., et al. (2019). 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. THE LANCET, 394(10204), 1169-1180 [10.1016/S0140-6736(19)31887-2].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/280365
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 598/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.
