Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial

Vranckx, Pascal; Valgimigli, Marco; Steg, Philippe Gabríel; Es, Gerrit Anne van; Möllmann, Helge; Abdellaoui, Mohamed; Adlam, David; Akın, İbrahim; Gonzalez‐Trevilla, Agustín Albarrán; Almeida, Manuel; Neto, Pedro Alves Lemos; Aminian, Adel; Anderson, Richard; Andreae, Rick; Angioı̈, Michaël; Asano, Taku; Barbato, Emanuele; Barlis, Peter; Barraud, Pascal; Benit, Edouard; Bertrand, Olivier; Beygui, Farzin; Bolognese, Leonardo; Botelho, Roberto; Bouwman, Coby; Bressers, Marco; Brunel, Philippe; Buszman, Paweł; Buysschaert, Ian; Silva, Pedro Canas da; Carrié, Didier; Cequier, Ángel; Chichareon, Ply; Chang, Chun Chin; Chowdhary, Saqib; Collet, Carlos; Colombo, Antonio; Cotton, James; Ferreira, Rui Cruz; Curello, Salvatore; Curzen, Nick; Bot, Judith de; Vreede, Tone de; Karth, Georg Delle; Dijksma, Lynn; Dominici, Marcello; Édes, István; Eeckhout, Éric; Eitel, Ingo; Faluközy, József; Fath‐Ordoubadi, Farzin; Ferrario, Maurizio; Fontos, Géza; Díaz, J.F. Jiménez; Quintella, Edgard Freitas; Frey, Bernhard; Friedrich, Guy; Galasko, Gavin; Gałuszka, Grzegorz; Ribeiro, Vasco Gama; Garg, Scot; Gargiulo, Giuseppe; Geisler, Tobias; Гелев, Валери; Ghandilyan, Art; Goicolea, Javier; Gori, Tommaso; Gragnano, Felice; Guimarães, Ana; Hamm, Christian W.; Haude, Michael; Heg, Dik; Heijke, Pieter; Antolín, R.A. Hernández; Hildick‐Smith, David; Hillen, Dorien; Hoekman, Ina; Hofma, Sjoerd H.; Holmvang, Lene; Hoole, Stephen P.; Horváth, Iván; Huber, Kurt; Hugense, Annemarie; Ibrahim, Karim; Íñiguez, Andrés; Isaaz, Karl; Jambrik, Zoltán; Janssens, Luc; Jasionowicz, Pawel; Jonk, Judith; Jung, Werner; Jüni, Peter; Katagiri, Yuki; Kogame, Norihiro; Koh, Tian Hai; Köning, René; Konteva, Mariana; Kőszegi, Zsolt; Krackhardt, Florian; Kreuger, Yvonne; Kukreja, Neville; Ladan, Boudijn; Lantelme, Pierre; Leandro, Sérgio M.; Leibundgut, Gregor; Liebetrau, Christoph; Lindeboom, Wietze; Miguel, Carlos Macaya; Mach, François; Magro, Michael; Maillard, Luc; Manavifar, Negar; Mauri, Laura; McFadden, Eugène; Merkely, Béla; Miyazaki, Yosuke; Młodziankowski, Adam; Moccetti, Tiziano; Modolo, Rodrigo; Möllman, Helge; Morelle, Jean‐François; Moschovitis, Aris; Ottesen, Michael Munndt; Muurling, Martin; Naber, Christoph; Neumann, Franz‐Josef; Oldroyd, Keith G.; Ong, Paul Jau Lueng; Onuma, Yoshinobu; Palsrok, Sanne; Petrov, Ivo; Planté, Sylvain; Prokopczuk, Janusz; Rademaker‐Havinga, Tessa; Raffel, C.; Rensing, Benno; Roffi, Marco; Royaards, Kees‐Jan; Sabaté, Manel; Schächinger, Volker; Seidler, Tim; Peñaranda, Antonio Serra; Serruys, Patrick W.; Sikarulidze, Lali; Slagboom, Ton; Soliman, Osama Ibrahim Ibrahim; Sousa, Amanda; Spitzer, Ernest; Stables, Rod; Steg, Gabriel; Steinwender, Clemens; Subkovas, Eduardas; Suryapranata, Harry; Takahashi, Kuniaki; Talwar, Suneel; Teiger, Emmanuel; Weele, Addy ter; Teurlings, Eva; Thury, Attila; Tijssen, Jan G.P.; Tonev, Gincho; Trendafilova‐Lazarova, Diana; Tumscitz, Carlo; Umans, Victor; Ungi, Imre; Valkov, Veselin; Harst, Pim van der; Geuns, Robert Jan van; Meijeren, Cokky van; Vassilev, Dobrin; Velchev, Vasil; Velthuizen, Esther; Verheugt, Freek W. A.; Vlcek, Natalia; Dahl, Jürgen vom; Vrolix, Mathias; Walsh, Simon; Werner, Nikos; Windecker, Stephan; Witsenburg, Maarten; Zaman, Azfar; Żmudka, Krzysztof; Zrenner, Bernhard; Żurakowski, Aleksander; Zweiker, Robert

doi:10.1016/s0140-6736(18)31858-0

Cited by 640 publications

(531 citation statements)

References 27 publications

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“…Such a benefit was not borne out in the GLOBAL LEADERS trial in a general post-PCI population. 30,31 The ongoing TWILIGHT trial is testing a similar strategy. 32 In conclusion, in patients with stable coronary artery disease and type 2 diabetes who did not have a history of myocardial infarction or stroke, ticagrelor plus aspirin was associated with a lower incidence of ischemic events than placebo plus aspirin at the expense of a higher incidence of major bleeding, including intracranial hemorrhage.…”

Section: Discussionmentioning

confidence: 99%

Ticagrelor in Patients with Stable Coronary Disease and Diabetes

et al. 2019

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BACKGROUNDPatients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear. METHODSIn this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria. RESULTSA total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P = 0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P = 0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P = 0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02). CONCLUSIONSIn patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.)A BS TR AC T

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Section: Discussionmentioning

confidence: 99%

Ticagrelor in Patients with Stable Coronary Disease and Diabetes

et al. 2019

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“…As described in Figure 1 patients met our eligibility criteria. [11][12][13][14] Of these, 14 530 patients were randomized to monotherapy with a P2Y12 inhibitor, whereas 14 599 patients were randomized to standard dual antiplatelet therapy. Four trials tested P2Y12 inhibitor monotherapy after 1 to 3 month of DAPT vs P2Y12 inhibitor plus aspirin ( Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…The TWILIGHT study, enrolled patients undergoing PCI who are at high risk for ischemic or hemorrhagic complications, was associated with a 51% lower risk of bleeding. In contrast to these three studies, the results of The GLOBAL LEADERS trial showed that DAPT for 1 month followed by 23 months of ticagrelor alone did not reduce the incidence of bleeding than the traditional DAPT treatment regimen . Patients included in this analysis mainly were treated with ticagrelor alone after 1 to 3 month of P2Y12 inhibitors plus aspirin.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to these three studies, the results of The GLOBAL LEADERS trial showed that DAPT for 1 month followed by 23 months of ticagrelor alone did not reduce the incidence of bleeding than the traditional DAPT treatment regimen. 11 Patients included in this analysis mainly were treated with ticagrelor alone after 1 to 3 month of P2Y12 inhibitors plus aspirin. These findings may be attributable to the differences in the research design, type of P2Y12 inhibitors, duration of therapy after randomization, and so on.…”

Section: Platelet Activation and Aggregation Play Key Roles In Initiamentioning

confidence: 99%

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The efficacy and safety of P2Y12 inhibitor monotherapy in patients after percutaneous coronary intervention

Luo

et al. 2019

Clinical Cardiology

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The optimal antiplatelet therapy after percutaneous coronary intervention (PCI) remains to be elucidated. Monotherapy with a P2Y12 inhibitor may be inferior to dual antiplatelet therapy in patients after PCI. PubMed, EMBASE (by Ovidsp), Web of Science, and The Cochrane Library were searched from database inception to 2 October 2019. The composite of cardiovascular outcomes, all‐cause mortality, myocardial infarction (MI), stroke, stent thrombosis, and major bleeding were evaluated. Pooled outcomes were presented as relative risk (RR) and 95% confidence intervals (CIs). A total of four trials randomizing 29 089 participants were included. Compared with the dual antiplatelet therapy group (n = 14 559), the P2Y12 inhibitor monotherapy group (n = 14 530) significantly decreased the incidence of bleeding events (2.0% vs 3.1%; RR: 0.60; 95% CI: 0.43‐0.84; P = .005). There were no significant differences in all‐cause mortality (1.3% vs 1.5%; RR: 0.87; 95% CI, 0.71‐1.06; P = .16), myocardial infarction (2.1% vs 1.9%; RR, 1.06; 95% CI, 0.90‐1.25; P = .46), stroke (0.6% vs 0.5%; RR, 1.18; 95% CI, 0.67‐2.07; P = .57), or stent thrombosis (0.5% vs 0.4%; RR, 1.14; 95% CI, 0.81‐1.61; P = .44) between the two groups. P2Y12 inhibitor monotherapy did not show any significant difference in the adverse cardiac and cerebrovascular events, but markedly decreased the risk of bleeding among patients after PCI vs dual antiplatelet therapy. However, it still needs to be further confirmed due to limited data.

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“…22 The I-LOVE-IT 2 study (sirolimus BP-DES) showed no significant difference in TLF and total adverse events between the 6-and 12-month DAPT groups. 23 The GLOBAL LEADERS study (biolimus BP-DES) compared 1-month DAPT, followed by ticagrelor monotherapy with standard 1-year DAPT, and found no difference between cardiovascular events and ST, 24 which also indicated the possibility of short-term DAPT. More evidence is still required to prove whether short-term DAPT is feasible for EXCROSSAL.…”

Section: Clinical Outcomesmentioning

confidence: 99%

Three‐year follow up of biodegradable polymer cobalt‐chromium sirolimus‐eluting stent (EXCROSSAL) in treating de novo coronary artery disease: Pooled analysis of CREDIT II and CREDIT III trials

Wang

Tao

et al. 2020

Cathet Cardio Intervent

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Objectives To analyze the 3‐year outcomes of the biodegradable polymer cobalt‐chromium sirolimus‐eluting stent (EXCROSSAL) in CREDIT II AND III TRIALS. Background Though approved by CFDA, the long‐term safety and efficacy of EXCROSSAL is still unknown. Methods CREDIT II was a randomized trial comparing the EXCROSSAL versus EXCEL stents in patients with up to two de novo coronary lesions, and CREDIT III was a prospective, single‐arm study evaluating the efficacy and safety of EXCROSSAL in broad types of de novo coronary artery lesions. We pooled the 3‐year follow‐up data of the EXCROSSAL arm of the CREDIT II and CREDIT III Trials. The primary outcome was 3‐year target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV‐MI), and clinically indicated target lesion revascularization (CI‐TLR). The patient‐oriented composite endpoint (PoCE) (all‐cause death, all MI, or any revascularization) and stent thrombosis (ST) were also analyzed. Results A total of 833 patients were included in this study. The incidence of TLF and PoCE in the 3‐year follow‐up were 7.6% and 12.5%, respectively. ST occurred in 0.6% of patients. In the subgroup analyses, TLF was significantly higher in small target vessels, multi‐lesion PCI, and multi‐vessel disease. Conclusions The 3‐year follow‐up analysis confirmed low rates of TLF and ST in EXCROSSAL, which is similar to the most widely used new generation durable polymer drug‐eluting stent.

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Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial

Abstract: AstraZeneca, Biosensors, and The Medicines Company.

Cited by 640 publications

References 27 publications

Ticagrelor in Patients with Stable Coronary Disease and Diabetes

Ticagrelor in Patients with Stable Coronary Disease and Diabetes

The efficacy and safety of P2Y12 inhibitor monotherapy in patients after percutaneous coronary intervention

Three‐year follow up of biodegradable polymer cobalt‐chromium sirolimus‐eluting stent (EXCROSSAL) in treating de novo coronary artery disease: Pooled analysis of CREDIT II and CREDIT III trials

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