Angiographic and electrocardiographic parameters of myocardial reperfusion in angioplasty of patients with ST elevation acute myocardial infarction loaded with ticagrelor or clopidogrel (MICAMI—TICLO trial)

Winter, José Luis; Lindefjeld, Dante; Veas, Nicolás; Guarda, Eduardo; Valdebenito, Martín; Méndez, Manuel; Pérez, Osvaldo; Zuanic, Karla; Mestas, María; Martínez, Alejandro

doi:10.1016/j.carrev.2014.07.001

Cited by 19 publications

(23 citation statements)

References 24 publications

(26 reference statements)

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“…As differences in angiographic findings, secondary to greater platelet inhibition, cannot explain the differences in clinical outcomes between ticagrelor and clopidogrel in the PLATO trial, 30,31 our study may provide an alternative explanation. In addition to its antiplatelet effects, ticagrelor provides cardioprotection against ischemia-reperfusion injury and improve long-term remodeling after infarction.…”

Section: Discussionmentioning

confidence: 79%

“…The recent Administration of Ticagrelor in the Cath Laboratory or in the Ambulance for New ST-Elevation Myocardial Infarction to Open the Coronary Artery (ATLANTIC) trial failed to show a clear clinical benefit in patients with STEMI undergoing pPCI and receiving ticagrelor en route to the hospital versus in the catheterization laboratory. 16 The myocardial reperfusion in angioplasty of patients with STEMI loaded with ticagrelor or clopidogrel (MICAMI-TICLO) trial 31 showed that ticagrelor loading before pPCI for STEMI did not improve angiographic findings or ST-segment elevation resolution, as compared with clopidogrel loading. In both trials, the time from drug loading to intervention was short (31-43 minutes).…”

Section: Discussionmentioning

confidence: 99%

“…In both trials, the time from drug loading to intervention was short (31-43 minutes). 16,31 It is plausible that the time between dose and pPCI in the in-ambulance study arm was insufficient to allow significant ticagrelor exposure at the time of pPCI to induce adenosine-dependent protection against the acute reperfusion injury, as shown in the current rat study. The MICAMI-TICLO trial was relatively small and did not follow the patients for clinical outcomes.…”

mentioning

confidence: 84%

“…The MICAMI-TICLO trial was relatively small and did not follow the patients for clinical outcomes. 31 However, both groups in the ATLANTIC trial received chronic ticagrelor treatment; hence, both groups benefited from the long-term effects of the drug. Therefore, no between-group difference could be seen.…”

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confidence: 99%

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Ticagrelor Protects the Heart Against Reperfusion Injury and Improves Remodeling After Myocardial Infarction

Ye¹,

Birnbaum

Perez‐Polo

et al. 2015

ATVB

108

111

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Objective-In addition to P2Y 12 receptor antagonism, ticagrelor inhibits adenosine cell uptake. Prior data show that 7-day pretreatment with ticagrelor limits infarct size. We explored the acute effects of ticagrelor and clopidogrel on infarct size and potential long-term effects on heart function. Approach and Results-Rats underwent 30-minute ischemia per 24-hour reperfusion. (1) Ticagrelor (10 or 30 mg/kg) or clopidogrel (12.5 mg/kg) was given via intraperitoneal injection 5 minutes before reperfusion. (2) Rats received ticagrelor acute (intraperitoneal; 30 mg/kg), chronic (oral; 300 mg/kg per day) for 4 weeks starting 1 day after reperfusion or the combination (acute+chronic). Another group received clopidogrel (intraperitoneal [12.5 mg/kg]+oral [62.5 mg/kg per day]) for 4 weeks.(1) Ticagrelor dose-dependently reduced infarct size, 10 mg/kg (31.5%±1.8%; P<0.001) and 30 mg/ kg (21.4%±2.6%; P<0.001) versus control (45.3±1.7%), whereas clopidogrel had no effect (42.4%±2.6%). Ticagrelor, but not clopidogrel, increased myocardial adenosine levels, increased phosphorylation of Akt, endothelial NO synthase, and extracellular-signal-regulated kinase 1/2 4 hours after reperfusion and decreased apoptosis. (2) After 4 weeks, left ventricular ejection fraction was reduced in the vehicle-treated group (44.8%±3.5%) versus sham (77.6%±0.9%).All ticagrelor treatments improved left ventricular ejection fraction, acute (69.5%±1.6%), chronic (69.2%±1.0%), and acute+chronic (76.3%±1.2%), whereas clopidogrel had no effect (37.4%±3.7%). Ticagrelor, but not clopidogrel, attenuated fibrosis and decreased collagen-III mRNA levels 4 weeks after ischemia/reperfusion. Ticagrelor, but not clopidogrel, attenuated the increase in proinflammatory tumor necrosis factor-α, interleukin-1β, and interleukin-18, and increased anti-inflammatory 15-epi-lipoxin-A 4 levels. Conclusions-Ticagrelor, but not clopidogrel, administered just before reperfusion protects against reperfusion injury. This acute treatment or chronic ticagrelor for 4 weeks or their combination improved heart function, whereas clopidogrel, despite achieving a similar degree of platelet inhibition, had no effect. addition to platelet inhibition, ticagrelor, but not clopidogrel, has protective effects against ischemia-reperfusion that may help explain the differences in clinical benefit in the PLATO trial. 7,8 However, a recent multicenter, randomized, double-blind clinical trial did not show a clear clinical benefit in patients with STEMI receiving ticagrelor en route to the hospital versus in the catheterization laboratory. 16 As the study was not powered for benefit on cardiovascular events, it is inconclusive about the hypothesis that administration of ticagrelor after onset of ischemia (in contrast to pretreatment just before reperfusion) can ameliorate reperfusion injury. In addition, as the median time difference between the prehospital and the in-hospital ticagrelor administration groups was only 31 minutes, 16 it is plausible that ticagrelor absorption was insufficient an...

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 84%

mentioning

confidence: 99%

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Ticagrelor Protects the Heart Against Reperfusion Injury and Improves Remodeling After Myocardial Infarction

Ye¹,

Birnbaum

Perez‐Polo

et al. 2015

ATVB

108

111

View full text Add to dashboard Cite

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“…These experimental studies in animals 30-32 were corroborated in healthy volunteers and ACS patients 7,9,33,10 showing enhanced coronary blood flow and improvement of peripheral and coronary microvascular function 34 . In contrast, the absence of a differential effect on microand macrovascular function and the inability to improve myocardial reperfusion with ticagrelor has also been reported [35][36][37] . In the present study we could not detect a difference in adenosine plasma concentrations during ticagrelor or prasugrel maintenance therapy.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Microvascular Injury in Revascularized Patients With ST-Segment–Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel

et al. 2019

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Background: Despite successful restoration of epicardial vessel patency with primary percutaneous coronary intervention (pPCI), coronary microvascular injury (MVI) occurs in a large proportion of STEMI patients, adversely affecting clinical and functional outcome. Ticagrelor has been reported to increase plasma adenosine levels, which might have a protective effect on the microcirculation. We investigated if ticagrelor maintenance therapy after revascularized STEMI is associated with less MVI compared to prasugrel maintenance therapy. Methods: A total of 110 STEMI patients received a loading dose of ticagrelor and were randomized to maintenance therapy of ticagrelor (n=56) or prasugrel (n=54) after pPCI. The primary outcome was MVI at 1 month, as determined with the index of microcirculatory resistance (IMR) in the infarct-related artery. Cardiovascular magnetic resonance imaging was performed during the acute phase and at one month. Results: The primary outcome of IMR was not superior in ticagrelor or prasugrel treated patients (ticagrelor 21 [15-39] U, prasugrel 18 [11-29] U, p=0.08). Recovery of microcirculatory resistance over time was not better in patients with ticagrelor versus prasugrel (ticagrelor-13.9 U vs. prasugrel-13.5 U, p=0.54). Intramyocardial hemorrhage was observed less frequently in patients with ticagrelor (23% vs. 43%, p=0.04). At one month no difference in infarct size was observed (ticagrelor 7.6 [IQR 3.7-14.4] g, prasugrel 9.9 [IQR 5.7-16.6] g, p=0.17). The occurrence of microvascular obstruction was not different in patients on ticagrelor (28%) or prasugrel (41%, p=0.35). Plasma adenosine concentrations were not different during the index procedure and during maintenance therapy with ticagrelor or prasugrel. Conclusions: In patients with STEMI, ticagrelor maintenance therapy was not superior to prasugrel in preventing MVI in the infarct-related territory as assessed by IMR and this resulted in a comparable infarct size at one month.

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Meta-analysis Comparing Outcomes of Type 2 Myocardial Infarction and Type 1 Myocardial Infarction With a Focus on Dual Antiplatelet Therapy

et al. 2020

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Background: There are important knowledge gaps in type 2 myocardial infarction (T2MI). Our primary objective was to compare the outcomes of patients with T2MI with those of patients with type 1 myocardial infarction (T1MI). Our secondary objective was to determine whether randomized controlled trials (RCTs) evaluating dual antiplatelets (DAPTs) have explicitly included patients with T2MI. Methods: We performed a meta-analysis comparing outcomes of patients with T2MI with patients with T1MI and a separate systematic review to evaluate the inclusion of T2MI in RCTs evaluating DAPT. There were 19 cohorts enrolling 48,829 patients (40,604 with T1MI and 5361 with T2MI) and 51 RCTs enrolling 188,132 patients with acute coronary syndrome.CJC Open 2 (2020) 118e128

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Angiographic and electrocardiographic parameters of myocardial reperfusion in angioplasty of patients with ST elevation acute myocardial infarction loaded with ticagrelor or clopidogrel (MICAMI—TICLO trial)

Cited by 19 publications

References 24 publications

Ticagrelor Protects the Heart Against Reperfusion Injury and Improves Remodeling After Myocardial Infarction

Ticagrelor Protects the Heart Against Reperfusion Injury and Improves Remodeling After Myocardial Infarction

Evaluation of Microvascular Injury in Revascularized Patients With ST-Segment–Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel

Meta-analysis Comparing Outcomes of Type 2 Myocardial Infarction and Type 1 Myocardial Infarction With a Focus on Dual Antiplatelet Therapy

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