Signaling via P2Y12 May Be Critical for Early Stabilization of Platelet Aggregates

Speich, Henry E.; Bhal, Vinay; Houser, Kourtney; Caughran, Alex T.; Lands, Lindsey T.; Houng, Aiilyan K.; Bäckström, Jonas; Enerbäck, Malin; Reed, Guy L.; Jennings, Lisa K.

doi:10.1097/fjc.0000000000000076

Cited by 12 publications

(9 citation statements)

References 32 publications

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“…There are some limited data that reversible P2Y 12 inhibitors may not be effective at dispersing established arterial thrombi and thus cangrelor may have a lower risk of re-bleeding in stenting performed in patients with ruptured aneurysms. 18…”

Section: Discussionmentioning

confidence: 99%

Cangrelor dose titration using platelet function testing during cerebrovascular stent placement

et al. 2020

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Background Optimal antiplatelet inhibition is vital during cerebrovascular stenting procedures, yet no standardized recommendation exists for antithrombotic therapy in these scenarios. Cangrelor is an intravenous P2Y12 inhibitor with a favorable pharmacokinetic profile for use during neuroendovascular stenting. Methods A retrospective review of all neuroendovascular patients who underwent stenting between 1 January 2019 and 22 March 2020 and were treated with cangrelor was conducted. Thirty-seven patients met inclusion criteria. Results All patients were administered a bolus of 5 mcg/kg of cangrelor followed by a maintenance infusion. Antiplatelet effects of cangrelor were monitored using platelet reactivity units (PRU). Based on the initial PRU, seven patients’ doses were adjusted with subsequent PRUs in or near the goal range of 50–150. One patient experienced an acute intraprocedural occlusion likely related to a subtherapeutic PRU which subsequently resolved with cangrelor dose adjustment and intra-arterial tirofiban administration, and one patient experienced a post-procedure stent occlusion which required a thrombectomy and intra-arterial tirofiban administration. No hemorrhagic complications occurred. Discussion Cangrelor utilization during neuroendovascular stenting with maintenance doses of <2 mcg/kg/min with dose adjustments based on platelet function testing has not been previously described. Cangrelor presents many advantages compared to standard therapy in patients undergoing stent placement related to its pharmacokinetic profile, rapid onset of action, ease of transition to oral P2Y12 antiplatelet agents, and measurability. Conclusion Cangrelor is a promising alternative to currently available therapies, especially in patients with a high hemorrhagic risk.

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Section: Discussionmentioning

confidence: 99%

Cangrelor dose titration using platelet function testing during cerebrovascular stent placement

et al. 2020

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“…e presence of coronary thrombus at the time of angiography is known to worsen outcomes following ACS [14]. Furthermore, in vitro models have shown that P2Y 12 agents can disrupt and even reverse thrombus stability [15,16]. Longer pretreatment with P2Y12 agents is also associated with improved coronary perfusion before PCI [17].…”

Section: Benefits Of Early Versus Delayed Angiographymentioning

confidence: 99%

464Optimal timing of invasive coronary angiography following NSTEMI

Mahendiran

Nanchen

Meier

et al. 2019

European Heart Journal

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Introduction Current guidelines recommend angiography within 24 hours of hospitalisation for patients with non-ST elevation myocardial infarction (NSTEMI). The recent VERDICT study found that angiography within 12 hours of hospitalisation was associated with improved cardiovascular outcomes among high-risk patients. We aimed to obtain a real-world perspective of the impact of angiography timing on one-year outcomes of patients admitted with NSTEMI. Methods Data was obtained from the SPUM-ACS registry, a cohort of consecutive patients hospitalised with acute coronary syndromes in four university hospitals in Switzerland between 2009 and 2017. Patients without a door-to-catheter (DTC) time and those with life-threatening features were excluded. Cox proportional hazards models evaluated the impact of DTC time on the primary endpoint, defined as one-year major adverse cardiovascular events (MACE: cardiovascular mortality, myocardial infarction, stroke), and on one-year all-cause mortality. Results Of 2,672 NSTEMI patients, 1,832 met the inclusion criteria. Among them, 1,464 patients underwent angiography within 12 hours of admission (12h group) while 368 patients underwent angiography between 12 and 24 hours (12–24h group). After 2:1 propensity score matching, 736 patients from the 12h group and 368 patients from the 12–24h group were deemed equivalent in terms of main baseline clinical characteristics. Multiple logistic regression identified admission out-of-hours (night or weekend) as the most significant factor associated with delayed angiography. Cox models found no significant association between early angiography and one-year MACE (12h group: n=57 (7.7%) vs. 12–24h group: n=27 (7.3%), HR: 1.050, 95% CI 0.637- 1.733, p=0.847), or one-year all-cause mortality (12h group: n=25 (3.4%) vs. 12–24h group: n=17 (4.6%), HR: 1.514, 95% CI 0.774- 2.962, p=0.225) (Figure 1A). After stratification based on GRACE score (>140 vs. ≤140), there was no significant difference in one-year MACE or one-year all-cause mortality in the 12h group compared with the 12–24h group (p for interaction=0.601 and 0.463, respectively) (Figure 1A + 1B). Figure 1 Conclusion In an unselected real-world cohort of NSTEMI patients, angiography within 12 hours of hospitalisation was not associated with improved one-year outcomes when compared with angiography between 12 and 24 hours, even among patients with an elevated GRACE score.

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“…A phase I study in humans showed that Revacept dose-dependently inhibited collagen-induced platelet aggregation without a significant effect on bleeding time. In contrast, ADP- or thrombin receptor activating peptide-dependent platelet aggregation remained unaltered [ 66 ].…”

Section: Novel Antithrombotic Drugs That May Impact On Thrombus Stabimentioning

confidence: 99%

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

Gorog

2018

J Thromb Thrombolysis

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The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.

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Signaling via P2Y12 May Be Critical for Early Stabilization of Platelet Aggregates

Cited by 12 publications

References 32 publications

Cangrelor dose titration using platelet function testing during cerebrovascular stent placement

Cangrelor dose titration using platelet function testing during cerebrovascular stent placement

464Optimal timing of invasive coronary angiography following NSTEMI

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

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