ticagrelor and Diabetic-Cardiomyopathies

This study aimed to investigate the efficacy and safety of dual and triple antiplatelet therapy (DAPT and TAPT) in patients with diabetes and acute ST segment elevation myocardial infarction (D-STEMI), who had undergone primary percutaneous coronary intervention (PCI).. We designed a phase IV, single-centre, randomised, double-blind, placebo-controlled study. The D-STEMI patients (n = 258) were randomly divided into three groups. Control group A (85 patients), was treated with aspirin and clopidogrel; group B (87 patients) received aspirin, clopidogrel, and tirofiban; and group C (86 patients) were treated with aspirin, ticagrelor, and tirofiban. Patients in all three groups received oral DAPT, and patients in groups B and C received intravenous tirofiban when primary PCI was performed.. Compared to the findings in group A, the post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow in groups B and C increased significantly (TIMI grade 3 in groups A, B, C: 74%, 91%, and 98%, respectively; TIMI myocardial perfusion grade [TMPG] grade 3 in groups A, B, C: 59%, 86%, and 97%, respectively), and the incidence of major adverse cardiac events (MACE) decreased significantly (p < 0.05). Compared to the findings in group B, the rate of TMPG 3 in group C was significantly higher (p < 0.05) and the incidence of MACE was significantly lower (p < 0.05). Patients in group B exhibited minor bleeding; however, the incidence of mild to moderate bleeding in group C increased significantly (p < 0.05).. TAPT effectively improved the TIMI blood flow and TMPG and reduced the occurrence of MACE. Ticagrelor was more effective than clopidogrel in TAPT; however, when using the combination of aspirin, ticagrelor, and tirofiban, close monitoring is required for possible bleeding complications.

Topics: Adenosine; Aged; Aspirin; Clopidogrel; Diabetic Cardiomyopathies; Double-Blind Method; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Safety; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine; Tirofiban; Treatment Outcome; Tyrosine

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Humans; Male; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome

Ticagrelor, a P2Y12 receptor antagonist, and dapagliflozin, a sodium-glucose-cotransporter-2 inhibitor, suppress the activation of the NLRP3 inflammasome. The anti-inflammatory effects of dapagliflozin depend on AMPK activation. Also, ticagrelor can activate AMPK. We assessed whether dapagliflozin and ticagrelor have additive effects in attenuating the progression of diabetic cardiomyopathy in T2DM mice.. Eight-week-old BTBR and wild-type mice received no drug, dapagliflozin (1.5 mg/kg/day), ticagrelor (100 mg/kg/day), or their combination for 12 weeks. Heart function was evaluated by echocardiography and heart tissue samples were assessed for fibrosis, apoptosis, qRT-PCR, and immunoblotting.. Both drugs attenuated the progression of diabetic cardiomyopathy as evident by improvements in left ventricular end-systolic and end-diastolic volumes and left ventricular ejection fraction, which were further improved by the combination. Both drugs attenuated the activation of the NOD-like receptor 3 (NLRP3) inflammasome and fibrosis. The effect of the combination was significantly greater than each drug alone on myocardial tissue necrotic factorα (TNFα) and interleukin-6 (IL-6) levels, suggesting additive effects. The combination had also a greater effect on ASC, collagen-1, and collagen-3 mRNA levels than each drug alone. While both drugs activated adenosine mono-phosphate kinase (AMPK), only dapagliflozin activated mTOR and increased RICTOR levels. Moreover, only dapagliflozin decreased myocardial BNP and Caspase-1 mRNA levels, and the effects of dapagliflozin on NLRP3 and collagen-3 mRNA levels were significantly greater than those of ticagrelor.. Both dapagliflozin and ticagrelor attenuated the progression of diabetic cardiomyopathy, the activation of the NLRP3 inflammasome, and fibrosis in BTBR mice with additive effects of the combination. While both dapagliflozin and ticagrelor activated AMPK, only dapagliflozin activated mTOR complex 2 (mTORC2) in hearts of BTBR mice.

Topics: AMP-Activated Protein Kinases; Animals; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Disease Models, Animal; Disease Progression; Enzyme Activation; Fibrosis; Glucosides; Inflammasomes; Male; Mechanistic Target of Rapamycin Complex 2; Mice, Inbred C57BL; Myocytes, Cardiac; NLR Family, Pyrin Domain-Containing 3 Protein; Purinergic P2Y Receptor Antagonists; Signal Transduction; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ticagrelor; TOR Serine-Threonine Kinases; Ventricular Function, Left; Ventricular Remodeling