Diabetes-Related Factors and the Effects of Ticagrelor Plus Aspirin in the THEMIS and THEMIS-PCI Trials

Leiter, Lawrence A.; Bhatt, Deepak L.; McGuire, Darren K.; Teoh, Hwee; Fox, Keith; Simon, Tabassome; Mehta, Shamir R.; Lev, Eli I.; Kiss, Róbert Gábor; Dalby, Anthony J.; Bueno, Héctor; Ridderstråle, Wilhelm; Himmelmänn, Anders; Prats, Jayne; Liu, Yuyin; Lee, Jane; Amerena, John; Kosiborod, Mikhail; Steg, Philippe Gabríel

doi:10.1016/j.jacc.2021.03.298

Cited by 15 publications

(13 citation statements)

References 36 publications

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“…Additionally, the hypothetical diabetes-specific endothelial effects of ticagrelor might have also contributed to stronger reductions of the risk of CV death and coronary death in diabetic vs. non-diabetic participants of the PEGASUS-TIMI 54 trial with a history of myocardial infarction 1–3 years earlier receiving ticagrelor (60 or 90 mg b.d.) with aspirin vs. aspirin alone [ 6 ], as well as to a lower risk of ischemic CV events with ticagrelor (60 mg b.d., most prevalent dose) as an addition to aspirin in T2DM subjects with stable CAD after prior PCI without previous myocardial infarction or stroke in the THEMIS-PCI trial [ 10 , 73 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, in a GReek AntiPlatElet registry substudy, DAPT with newer P2Y 12 antagonists, but not clopidogrel, attenuated the negative impact of diabetes on ischemic CV events after ACS [ 9 ]. Additionally, net clinical benefits of ticagrelor plus aspirin compared to aspirin alone were reported in participants of the THEMIS-PCI trial with type 2 diabetes (T2DM) and stable coronary artery disease (CAD) with a history of previous percutaneous coronary intervention (PCI) but without prior myocardial infarction or stroke, regardless of diabetes duration or glycated hemoglobin levels [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Endothelial biomarkers and platelet reactivity on ticagrelor versus clopidogrel in patients after acute coronary syndrome with and without concomitant type 2 diabetes: a preliminary observational study

Chyrchel

Kruszelnicka

Surdacki

2022

Cardiovasc Diabetol

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Background Pleiotropic effects have been implicated in clinical benefits of ticagrelor compared to thienopyridine P2Y12 antagonists. There are conflicting data regarding effects of ticagrelor vs. thienopyridine P2Y12 blockers on endothelial function. Our aim was to compare endothelial biomarkers and their relations with platelet reactivity in real-world patients after acute coronary syndrome (ACS) on maintenance dual antiplatelet therapy (DAPT) with ticagrelor or clopidogrel stratified by diabetes status. Methods Biochemical indices of endothelial dysfunction/activation and platelet reactivity by multiple electrode aggregometry were compared in 126 stable post-ACS subjects (mean age: 65 ± 10 years, 92 men and 34 women), including patients with (n = 61) or without (n = 65) coexistent type 2 diabetes (T2DM) on uneventful maintenance DAPT with either ticagrelor (90 mg b.d.) or clopidogrel (75 mg o.d.) in addition to low-dose aspirin. Exclusion criteria included a complicated in-hospital course, symptomatic heart failure, left ventricular ejection fraction < 40% and relevant coexistent diseases except for well-controlled diabetes, mild renal insufficiency or hypertension. Results Clinical characteristics were similar in patients on ticagrelor (n = 62) and clopidogrel (n = 64). The adenosine diphosphate-induced platelet aggregation and circulating soluble P-selectin (sP-selectin) were decreased in ticagrelor users irrespective of T2DM status (p < 0.001 and p < 0.01 for platelet reactivity and sP-selectin, respectively). Plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were lower in T2DM subjects on ticagrelor vs. clopidogrel (758 ± 162 vs. 913 ± 217 µg/L, p < 0.01). In contrast, plasma sVCAM-1 was similar in non-diabetic patients on ticagrelor and clopidogrel (872 ± 203 vs. 821 ± 210 µg/L, p > 0.7). The concentrations of sE-selectin, monocyte chemoattractant protein-1 and asymmetric dimethylarginine did not differ according to the type of P2Y12 antagonist regardless of T2DM status. Platelet reactivity was unrelated to any endothelial biomarker in subjects with or without T2DM. Conclusions Our preliminary findings may suggest an association of ticagrelor-based maintenance DAPT with favorable endothelial effects compared to clopidogrel users in stable post-ACS patients with T2DM. If proven, this could contribute to more pronounced clinical benefits of ticagrelor in diabetic subjects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endothelial biomarkers and platelet reactivity on ticagrelor versus clopidogrel in patients after acute coronary syndrome with and without concomitant type 2 diabetes: a preliminary observational study

Chyrchel

Kruszelnicka

Surdacki

2022

Cardiovasc Diabetol

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“…On the other hand, DM was not identified as an independent predictor of in-hospital mortality in patients with acute coronary syndrome complicated by cardiogenic shock [ 39 ]. More aggressive pharmacotherapy might mitigate these detrimental effects of DM [ 12 , 13 , 14 ]. Unfortunately, the use of ticagrelor and prasugrel was low but comparable between the patients with and without DM.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, enhanced platelet adhesion, activation, and aggregation are observed in patients with DM, leading to an increased risk of periprocedural complications [ 8 , 9 , 10 , 11 ]. However, the influence of these factors might be mitigated by new treatment strategies and modern pharmacotherapy of STEMI [ 12 , 13 , 14 ]. Whether the impact of DM on outcomes of STEMI patients undergoing primary PCI is still present in unselected patients undergoing up-to-date treatment is unclear.…”

Section: Introductionmentioning

confidence: 99%

Diabetes Mellitus Is Still a Strong Predictor of Periprocedural Outcomes of Primary Percutaneous Coronary Interventions in Patients Presenting with ST-Segment Elevation Myocardial Infarction (from the ORPKI Polish National Registry)

Dziewierz

Zdzierak²,

Malinowski

et al. 2022

JCM

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The impact of diabetes mellitus (DM) on outcomes of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) was confirmed by several studies. However, it is unclear whether this effect is still present in large groups of unselected patients undergoing up-to-date treatment. Thus, we sought to assess the impact of DM on periprocedural outcomes of primary PCI in STEMI using data from the Polish National Registry of PCI. Data on 150,782 STEMI patients undergoing primary PCI were collected. Of them, 26,360 (17.5%) patients had DM. Patients with DM were higher-risk individuals who experienced longer reperfusion delays and were less likely to have closed infarct-related artery at baseline (TIMI 0 + 1 flow: 73.2% vs. 72.0%; p < 0.0001) and achieve optimal reperfusion after PCI (TIMI 3 flow: 91.8% vs. 88.5%; p < 0.0001). The periprocedural mortality (1.1% vs. 1.9%; p < 0.0001) was higher in patients with DM and DM was identified as an independent predictor of periprocedural death. In conclusion, despite continuous progress in STEMI treatment, DM remains a strong predictor of periprocedural mortality. However, this detrimental effect of DM may be partially explained by the overall higher risk profile of diabetic patients.

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“…Тем не менее, этот результат был достигнут за счет существенного увеличения числа больших кровотечений, и в результате суммарный клинический эффект (эффек-тивность+безопасность) комбинации АСК и тикагрелора в сравнении с АСК оказался нейтральным [21,22]. Следует отметить, однако, что в большом заранее запланированном субанализе подгруппы с ЧКВ в анамнезе (THEMIS-PCI) сочетание АСК и тикагрелора приводило к значимому улучшению суммарного клинического эффекта [23].…”

Section: Optimum Treatment Strategy In Chronic Coronary Syndromes оптимальная стратегия лечения хронического коронарного синдромаunclassified

Optimum Treatment Strategy in Chronic Coronary Syndromes: the New Trials vs the Current Guidelines

Берштейн¹,

Zbyshevskaya²,

Гумерова³

2021

Racionalʹnaâ farmakoterapiâ v kardiologii

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Coronary revascularization is one of the most studied types of interventions in cardiology, but there is no consensus among specialists about the indications for its implementation in patients with chronic coronary syndromes (CCS). The data of recently completed clinical trials on the role of revascularization in CCS clearly contradict the current Guidelines, emphasizing the high effectiveness of modern conservative therapy. This paper discusses the main recommendations of the most significant American and European Guidelines on myocardial revascularization, and also analyzes the appropriateness of revascularization to improve the prognosis and symptoms in chronic coronary syndromes in view of the new research data, primarily the ISCHEMIA study (NCT01471522). Its strengths and limitations are discussed in detail. The data on the expediency of revacularization in CCS, obtained after the completion of ISCHEMIA and its potential significance, as well as subgroup analyses of ISCHEMIA, including in the most important ‘problem’ subgroups (3-vessel disease, proximal LAD disease, severe ischemia on stress test, etc.) are discussed. The paper also discusses the important achievements in modern drug therapy of chronic coronary syndromes, primarily antithrombotic therapy. The data of the COMPASS study (NCT01776424) are discussed, based on which the addition of a second antithrombotic drug – rivaroxaban in a small dose (2.5 mg BID) – is recommended for patients with CCS without atrial fibrillation who have high-risk characteristics. Indications the administration of dual antithrombotic therapy to patients with CCS, comparative results of its various regimens in relation to the prevention of cardiovascular complications, the risk of bleeding and the net clinical effect are given.

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Diabetes-Related Factors and the Effects of Ticagrelor Plus Aspirin in the THEMIS and THEMIS-PCI Trials

Cited by 15 publications

References 36 publications

Endothelial biomarkers and platelet reactivity on ticagrelor versus clopidogrel in patients after acute coronary syndrome with and without concomitant type 2 diabetes: a preliminary observational study

Endothelial biomarkers and platelet reactivity on ticagrelor versus clopidogrel in patients after acute coronary syndrome with and without concomitant type 2 diabetes: a preliminary observational study

Diabetes Mellitus Is Still a Strong Predictor of Periprocedural Outcomes of Primary Percutaneous Coronary Interventions in Patients Presenting with ST-Segment Elevation Myocardial Infarction (from the ORPKI Polish National Registry)

Optimum Treatment Strategy in Chronic Coronary Syndromes: the New Trials vs the Current Guidelines

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