Cangrelor in Ticagrelor-Loaded STEMI Patients Undergoing Primary Percutaneous Coronary Intervention

Alexopoulos, Dimitrios; Pappas, Christos; Sfantou, Danai; Xanthopoulou, Ioanna; Didagelos, Matthaios; Kikas, Petros; Ziakas, Antonios; Tziakas, Dimitris; Karvounis, Haralambos; Iliodromitis, Efstathios K.

doi:10.1016/j.jacc.2018.07.041

Cited by 18 publications

(11 citation statements)

References 4 publications

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“…Applicability to ticagrelor loading, which is mostly used in clinical practice at the beginning of cangrelor infusion or before primary PCI, 39 , 40 cannot be claimed. However, on the basis of our observation that cangrelor followed by prasugrel associates with a rebound of platelet activation at 2 to 4 hours and on previous data showing some HRPR during and after cangrelor infusion, 32 , 34 one could speculate that when cangrelor is used, ticagrelor might be the preferred oral P2Y 12 inhibitor. It remains unclear whether the test-specific cutoffs used to define HRPR rates retain prognostic implications for the acute treatment of STEMI, considering that they were generated mainly for stable or stabilized patients receiving oral P2Y 12 inhibitors.…”

Section: Discussionmentioning

confidence: 61%

“… 33 It is interesting that 3 out of 22 patients remained nonresponders to cangrelor at vasodilator-stimulated phosphoprotein assay during drug infusion. 32 Alexopoulos et al 34 reported that HRPR was 6.7% at 15 minutes and 0% at 1 hour (using VerifyNow and a cutoff of PRU >208) in 15 patients with STEMI receiving cangrelor (pretreated with ticagrelor; none of them received morphine). Ubaid et al 35 reported an HRPR rate of 10% (using VerifyNow and a cutoff of PRU >208) at the time of balloon inflation in 50 cangrelor-treated patients with STEMI.…”

Section: Discussionmentioning

confidence: 99%

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Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment–Elevation Myocardial Infarction

et al. 2020

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Background: Standard administration of newer oral P2Y 12 inhibitors, including prasugrel or ticagrelor, provides suboptimal early inhibition of platelet aggregation (IPA) in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). We sought to investigate the effects of cangrelor, tirofiban and prasugrel, administered as chewed or integral loading dose, on IPA in patients undergoing primary PCI. Methods: The FABOLUS-FASTER is an investigator-initiated, multicenter, open-label, randomized study. A total of 122 P2Y 12 -naïve STEMI patients were randomly allocated (1:1:1) to cangrelor (n=40), tirofiban (n=40), both administered as bolus and 2h infusion followed by 60 mg of prasugrel, or 60 mg loading dose of prasugrel (n=42). The latter group underwent an immediate 1:1 sub-randomization to chewed (n=21), or integral (n=21) tablets administration. The trial was powered to test 3 hypotheses (non-inferiority of cangrelor compared with tirofiban using a non-inferiority margin of 9%, superiority of both tirofiban and cangrelor compared with chewed prasugrel and superiority of chewed prasugrel as compared with integral prasugrel; each with alpha of 0.016) for the primary endpoint that was 30-minute IPA at light transmittance aggregometry (LTA) in response to 20 μmol/L adenosine diphosphate (ADP). Results: At 30 min, cangrelor did not satisfy non-inferiority compared with tirofiban, which yielded superior IPA over cangrelor (IPA: 95.0±8.9 vs. 34.1±22.5; P<0.001); cangrelor or tirofiban were both superior to chewed prasugrel (IPA: 10.5±11.0, P<0.001 for both comparisons), which did not provide higher IPA over integral prasugrel (6.3±11.4; P=0.47), despite yielding higher prasugrel's active metabolite concentration (ng/ml; 62.3±82.6 vs 17.1±43.5; P=0.016). Conclusions: Cangrelor provided inferior IPA compared with tirofiban; both treatments yielded greater IPA compared with chewed prasugrel which led to higher active metabolite concentration but not greater IPA compared with integral prasugrel. Clinical Trial Registration: clinicaltrials.gov NCT02978040, and EudraCT 2017-001065-24

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment–Elevation Myocardial Infarction

et al. 2020

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“…In the first, 30 patients received ticagrelor loading prior to angiography and then were randomized in the catheter laboratory to either cangrelor or no additional anti-platelet treatment. 4 It showed markedly more potent P2Y12 inhibition (PRU) 15 minutes following loading in subjects treated with cangrelor. There was a suggestion, in this trial, of an increase in platelet reactivity following cessation of the cangrelor infusion with 4 out of 15 patients exhibiting an increase in PRU at 2 to 4 hours.…”

Section: Discussionmentioning

confidence: 98%

“…Intriguingly, in this study, a proportion of the patients receiving both agents exhibited an increase in platelet reactivity after stopping the cangrelor infusion. 4 In the recently published CANTIC study, 50 patients undergoing PPCI received crushed ticagrelor and were then randomized to be treated with simultaneous cangrelor or matching placebo. Cangrelor reduced the P2Y12 reaction unit (PRU) throughout the infusion, compared with placebo and consequently therefore high on-treatment platelet reactivity (HPR) rates were reduced in the cangrelor arm.…”

Section: Introductionmentioning

confidence: 99%

Cangrelor versus Ticagrelor in Patients Treated with Primary Percutaneous Coronary Intervention: Impact on Platelet Activity, Myocardial Microvascular Function and Infarct Size: A Randomized Controlled Trial

et al. 2019

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Background Oral P2Y12 inhibitors take more than 2 hours to achieve full effect in healthy subjects and this action is further delayed in patients with acute myocardial infarction. Intravenous P2Y12 inhibition might lead to more timely and potent anti-platelet effect in the context of emergency primary angioplasty, improving myocardial recovery. Objectives This article compares the efficacy of intravenous cangrelor versus ticagrelor in a ST-elevation myocardial infarction (STEMI) population treated with primary percutaneous coronary intervention (PPCI). Materials and Methods In an open-label, prospective, randomized controlled trial, 100 subjects with STEMI were assigned 1:1 to intravenous cangrelor or oral ticagrelor. The co-primary endpoints were platelet P2Y12 inhibition at infarct vessel balloon inflation time, 4 and 24 hours. Secondary endpoints included indices of coronary microcirculatory function: index of microvascular resistance (IMR), initial infarct size (troponin at 24 hours) and final infarct size at 12 weeks (cardiac magnetic resonance). Secondary endpoints included indices of coronary microcirculatory function (index of microvascular resistance [IMR]), initial infarct size (troponin at 24 hours), final infarct size at 12 weeks (cardiac magnetic resonance), corrected thrombolysis in myocardial infarction (TIMI) frame count, TIMI flow grade, myocardial perfusion grade, and ST-segment resolution (ClinicalTrials.gov NCT02733341). Results P2Y12 inhibition at first balloon inflation time was significantly greater in cangrelor-treated patients (cangrelor P2Y12 reaction unit [PRU] 145.2 ± 50.6 vs. ticagrelor 248.3 ± 55.1). There was no difference in mean PRU at 4 and 24 to 36 hours post-dosing. IMR, final infarct size, angiographic and electrocardiographic measures of reperfusion were all similar between groups. Conclusion Cangrelor produces more potent P2Y12 inhibition at the time of first coronary balloon inflation time compared with ticagrelor. Despite this enhanced P2Y12 inhibition, coronary microvascular function and final infarct size did not differ between groups.

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“…Alexopoulos et al 67 did a similar randomized study in a cohort of STEMI patients and made similar observations. Notably, neither Franchi 66 nor Alexopoulos 67 observed any major bleeding. Although Mohammad et al 68 did not randomize STEMI patients to either a cangrelor or placebo group, they observed continued blockade of platelet aggregation after the 2-hour cangrelor infusion was suspended as a result of ticagrelor administration 41 to 50 minutes before PCI.…”

Section: Cooperative Action Of Intravenous Cangrelor and Oral Ticagrelormentioning

confidence: 93%

What Are Optimal P2Y12 Inhibitor and Schedule of Administration in Patients With Acute Coronary Syndrome?

Cohen

Downey

2019

J Cardiovasc Pharmacol Ther

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Guidelines recommend treatment with a P2Y12 platelet adenosine diphosphate receptor inhibitor in patients undergoing elective or urgent percutaneous coronary intervention (PCI), but the optimal agent or timing of administration is still not clearly specified. The P2Y12 inhibitor was initially used for its platelet anti-aggregatory action to block thrombosis of the recanalized coronary artery or deployed stent. It is now recognized that these agents also offer potent cardioprotection against a reperfusion injury that occurs in the first minutes of reperfusion if platelet aggregation is blocked at the time of reperfusion. But this is difficult to achieve with oral agents which are slowly absorbed and often require time-consuming metabolic activation. Patients with ST-segment elevation myocardial infarction who usually have a large mass of myocardium at risk of infarction seldom have sufficient time for upstream-administered oral agents to achieve a therapeutic P2Y12 level of inhibition by the time of balloon inflation. However, optimal treatment could be assured by initiating an IV cangrelor infusion shortly prior to stenting followed by subsequent post-PCI transition to an oral agent, that is, ticagrelor, once success of the recanalization and absence of need for surgical intervention are confirmed. Not only should this sequence provide optimal protection against infarction, it should also negate bleeding if coronary artery bypass grafting should be required since stopping the cangrelor infusion at any time will quickly restore platelet reactivity. It is anticipated that cangrelor-induced myocardial salvage will help preserve myocardial function and significantly diminish postinfarction heart failure.

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Cangrelor in Ticagrelor-Loaded STEMI Patients Undergoing Primary Percutaneous Coronary Intervention

Cited by 18 publications

References 4 publications

Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment–Elevation Myocardial Infarction

Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment–Elevation Myocardial Infarction

Cangrelor versus Ticagrelor in Patients Treated with Primary Percutaneous Coronary Intervention: Impact on Platelet Activity, Myocardial Microvascular Function and Infarct Size: A Randomized Controlled Trial

What Are Optimal P2Y12 Inhibitor and Schedule of Administration in Patients With Acute Coronary Syndrome?

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