Management of peripheral arterial disease in the elderly
Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich in Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Antiplatelet drugs that have been shown to decrease the incidence of vascular death, nonfatal myocardial infarction, and nonfatal stroke in persons with PAD are aspirin, ticlopidine, clopidogrel, and ticagrelor (120–122). Aspirin plus dipyridamole has not been shown to be more efficacious than aspirin alone in the treatment of persons with PAD (120). Oral platelet glycoprotein IIb/IIIa inhibitors have been shown to increase mortality in the treatment of persons with CAD and have not been investigated in the treatment of persons with PAD (123). Adverse hematologic effects associated with ticlopidine limit the use of this drug in the treatment of elderly persons with PAD (124). Ticagrelor and clopidogrel are equally effective in reducing cardiovascular events and cause a similar incidence of major bleeding (122).
Briefing Therapeutic Approaches in Anticoagulant, Thrombolytic, and Antiplatelet Therapy
Debarshi Kar Mahapatra, Sanjay Kumar Bharti in Medicinal Chemistry with Pharmaceutical Product Development, 2019
ADP induced platelet aggregation takes place through binding of ADP to G protein-coupled P2Y purinergic receptors. Clopidogrel (Figure 7.13) is a thienopyridine that irreversibly inhibits P2Y12 on the platelet surface. It must be metabolized in the liver to generate the active metabolites that inhibit the ADP receptor [88]. New P2Y12 inhibitors include prasugrel, cangrelor, and ticagrelor (Figure 7.13). Like clopidogrel, prasugrel is a thienopyridine that requires hepatic metabolism to generate active metabolites. It is more efficient than that of clopidogrel. It produces more rapid, more consistent, and more potent inhibition of ADP-induced platelet aggregation. Cangrelor and ticagrelor are direct-acting reversible inhibitors of P2Y12. Cangrelor, which is administered intravenously, has a rapid onset and offset of action. Ticagrelor is administered orally [89, 90]. Elinogrel (Figure 7.13) is an experimental antiplatelet drug acting as a P2Y12 inhibitor. However, development was discontinued in 2012. Ticlopidine (Figure 7.13) is an antiplatelet drug in the thienopyridine family. However, because of its rare but serious side effects of neutropenia and thrombotic thrombocytopenic purpura, its use remained limited [91, 92].
Acute coronary syndrome: Acute ST-segment elevation myocardial infarction
Ever D. Grech in Practical Interventional Cardiology, 2017
Ticagrelor is a reversibly binding non-thienopyridine oral P2Y12-inhibitor which does not require hepatic biotransformation for activity. It is prescribed as a loading dose of 180 mg followed by 90 mg twice daily. In the PLATO trial, the primary end point at 12 months, a composite of death from vascular causes, myocardial infarction or stroke occurred in 9.8% of patients receiving ticagrelor compared with 11.7% of those receiving clopidogrel (p < .001). Major bleeding not related to coronary artery bypass grafting was significantly higher in the ticagrelor arm (4.5% vs. 3.8%, p = 0.03). The mortality rate, a pre-specified secondary endpoint, was also significantly lower in the ticagrelor group. Side effects of ticagrelor include dyspnoea and ventricular pauses. Dyspnoea was present in 13.8% of patients with no compromise of pulmonary function, due to adenosine deaminase inhibition causing higher levels of adenosine. There was also a higher incidence of ventricular pauses in the first week which resolved at 30 days. There was no significant increase in syncope or pacemaker implantation in patients receiving clopidogrel or ticagrelor.23
Ticagrelor for the prevention of ischemic events in patients with prior myocardial infarction and peripheral artery disease
Published in Expert Opinion on Pharmacotherapy, 2018
José C. Nicolau, Luciano M. Baracioli, Robert P. Giugliano
Patients with MI comprise a population with a high risk of subsequent atherothrombotic events; the same is true for patients with PAD. The concomitant presence of both diagnoses significantly increases the patient’s risk, when compared to each one individually. Ticagrelor is a compound representative of a new generation of reversibly antiplatelet drugs. It is not a prodrug, having a rapid onset of action and a potent and consistent antiplatelet effect. In patients with ACS, ticagrelor 90 mg BID was superior to clopidogrel 75 mg daily for one year of follow up [29]. In stable patients with an MI 1–3 years prior, ticagrelor 90 mg BID or 60 mg BID on top of aspirin was superior to placebo [16]. The 60 mg BID dose was approved for this indication in North-America and Europe. Importantly, given the higher risk of patients with MI and PAD concomitantly, sub-analyses of these studies suggest a greater benefit of ticagrelor in this very high-risk population [17,37]. In EUCLID [46], which included patients with symptomatic PAD, the composite primary end point of the study was not significantly different in the ticagrelor and clopidogrel groups. It is important to note that only 17.9% of the population had previous MI, and significant interactions were observed for history of coronary carotid revascularization and history of coronary stent implantation (P-interaction = 0.03 for both), which may suggest a benefit of ticagrelor in patients with polyvascular disease. In secondary analyses, ticagrelor significantly decreased the incidence of stroke (HR = 0.78, P = 0.03).
Ticagrelor in modern cardiology - an up-to-date review of most important aspects of ticagrelor pharmacotherapy
Published in Expert Opinion on Pharmacotherapy, 2018
Dorota Danielak, Marta Karaźniewicz-Łada, Franciszek Główka
Earliest results from the PLATO trial showed that the efficacy of ticagrelor in ACS patients with creatinine clearance <60 ml/min was greater than that of clopidogrel [84]. Ticagrelor successfully reduced the occurrence of cardiovascular death, myocardial infarction or stroke within 12 months of the treatment (17.3% vs. 22.0%). Interestingly, the absolute risk reduction was more pronounced in patients with chronic kidney disease than in individuals with normal renal function. Similar results were obtained in the PEGASUS-TIMI 54 trial [85]. While the relative reduction in major adverse cardiovascular events with ticagrelor was similar in patients with normal and impaired renal function (estimated glomerular filtration rate <60 ml/min/1.73 m2), the absolute risk reduction was greater in the latter group. This observation was explained by the fact that patients with decreased renal function were generally at a greater risk of cardiovascular death, myocardial infarction or stroke. They were also more prone to minor bleeding events (1.93% vs. 0.69%). Even though renal failure might have a negative influence on the long-term survival of patients with ACS, the platelet reactivity in this group of patients appears to be similar to the reactivity reported in patients with normal renal function [86]. Likewise, the benefits of ticagrelor over clopidogrel and prasugrel, such as faster onset and offset of antiplatelet effect and greater reduction of platelet reactivity are also reported in patients with chronic kidney disease [87,88].
Effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats
Published in Pharmaceutical Biology, 2020
Jia Chong, Hao Chen, Dapeng Dai, Shuanghu Wang, Quan Zhou, Junpeng Liu, You Lü, Hualan Wu, Minghui Du, Feifei Chen, Hui Jiang, Yunfang Zhou, Jiefu Yang
Combination of rivaroxaban with ticagrelor may cause potent antithrombotic effects. Rivaroxaban potently inhibits prothrombinase complex-bound factor Xa on the surface of activated platelets, thus inhibits thrombin generation and thrombin-induced platelet aggregation. Ticagrelor potently inhibits platelet activation, which may provide a catalytic surface for initiating and sustaining coagulation. Recently, it has been reported that rivaroxaban powerfully inhibited tissue factor-induced platelet aggregation in a concentration dependent manner and had a synergistic effect with ticagrelor (Perzborn et al. 2015). These findings may explain that very-low-dose rivaroxaban could reduce cardiovascular events in ACS patients. Our study revealed that the pharmacokinetic effects of ticagrelor on the metabolism of rivaroxaban raised rivaroxaban plasma concentration significantly in rats. The results demonstrated in our study and the pharmacodynamic interactions between rivaroxaban and ticagrelor suggest that caution should be paid when these two agents are co-administered in clinical practice, and rivaroxaban dose may need to be adjusted to minimize bleeding risk.
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