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Acute coronary syndromes
Published in Henry J. Woodford, Essential Geriatrics, 2022
Prasugrel following ACS, compared to clopidogrel, has a lower risk of cardiovascular adverse events but a higher risk of bleeding complications (n = 13,608; median age 61; 13% aged 75 or over).17 The maintenance dose of prasugrel should be reduced (from 10 to 5 mg daily) for people aged over 75 or those with a body weight less than 60 kg. It is not recommended for people with a past history of stroke. The reduced dose of prasugrel (5mg od) has been compared to clopidogrel following PCI for ACS in people aged 75 and over (mean age 80).18 The primary composite end-point of death, MI, disabling stroke, hospitalisation for cardiovascular causes or bleeding within a year was not significantly improved (17.0% v 16.6%). Reduced stent thrombosis (0.7% v 1.9%) was offset by more bleeding (4.1% v 2.1%). Prasugrel is unlikely to be used in frail older people unless there are contraindications to other drugs.
Antiplatelet therapy in interventional cardiology
Published in John Edward Boland, David W. M. Muller, Interventional Cardiology and Cardiac Catheterisation, 2019
The main concern with prasugrel is increased bleeding. In the TRITON-TIMI 38 trial, TIMI-major haemorrhage (not related to coronary artery bypass) occurred in 2.4% (prasugrel group) vs. 1.8% (clopidogrel group) with a hazard ratio, 1.32; 95% CI, 1.03 to 1.68; P = 0.03.24 The bleeding risk of prasugrel was also increased when bleeds were categorised into fatal and non-fatal.24 Data from TRITON-TIMI 38 has led to the American Geriatric Society (AGS) including prasugrel in the 2015, Beers Criteria, a list of potentially inappropriate medications to be avoided in older adults.27 The AGS have advised caution in using prasugrel in adults ≥75 years old given the smaller relative reduction in primary efficacy events, coupled with higher absolute TIMI major bleeding rates.24, 27 Additional patients with a known history of stroke or transient ischemic attack before enrolment in TRITON–TIMI 38 had an increase in stroke and higher rate of bleeding, in particular intracranial haemorrhage.24 Patients with low body weight (<60 kg) also have higher rates of bleeding.24 The most frequent side effects of prasugrel include: hypertension (7.5%), hyperlipidaemia (7%), headache (5.5%), back pain (5%), dyspnea (4.9%) and nausea (4.6%). Post-marking there have been reports of thrombotic thrombocytopenic purpura and hypersensitivity reactions including anaphylaxis.
Cardiovascular drug therapy in the elderly
Published in Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich, Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
William H. Frishman, Wilbert S. Aronow, Angela Cheng-Lai
Three oral P2Y12 inhibitors, clopidogrel prasugrel, and ticagrelor are currently available for use in the management of acute coronary syndrome (ACS) (172). Prasugrel is approved for use in patients with ACS undergoing percutaneous coronary interventions; this agent should be avoided in individuals ≥75 years of age since this population was found to benefit less from prasugrel with a greater risk of bleeding (173,174).
Treatment inequity in antiplatelet therapy for ischaemic heart disease in patients with advanced chronic kidney disease: releasing the evidence vacuum
Published in Platelets, 2023
Frances L. Varian, William A. E. Parker, James Fotheringham, Robert F. Storey
Prasugrel is a newer prodrug, with significantly enhanced potency in reduction of platelet activation compared to clopidogrel. Rapidly hydrolysed by intestinal hydroxyesterases followed by CYP bioactivation, maximum plasma concentration of the active metabolite is reached at 30–60 min [65]. Like clopidogrel, this third-generation thienopyridine blocks ADP binding to the P2Y12 receptor irreversibly and effectively reduces multiple aspects of platelet activation and associated responses [66]. Maximum effect of platelet inhibition after loading with 60 mg prasugrel is seen at 1 h compared to clopidogrel where maximum effects of a 300 mg loading dose are seen at >6 h and 600 mg at 2–4 h [65,67]. Furthermore, small studies suggest that low-dose prasugrel, as well as clopidogrel, demonstrates a reduction in platelet inhibition post-HD (mean P2Y12 reaction units >208), which requires further exploration [63].
Antithrombotic treatment in primary percutaneous coronary intervention
Published in Expert Review of Cardiovascular Therapy, 2021
Felix Voll, Constantin Kuna, Gjin Ndrepepa, Adnan Kastrati, Salvatore Cassese
Ticagrelor and prasugrel represent the third-generation, more potent and faster acting P2Y12-receptor inhibitors [51]. The direct-acting, oral cyclo-pentyltriazolo-pyrimidine ticagrelor reversibly blocks the P2Y12-receptor on platelets [52]. In contrast, prasugrel is a thienopyridine pro-drug with a single-step CYP-dependent bio-activation, providing irreversible P2Y12-receptor inhibition [53]. As compared to clopidogrel, both ticagrelor and prasugrel reduced the risk of ischemic events in patients with MI, including those with STEMI treated with pPCI [54,55]. Despite a slight increase in the risk of significant bleeding, the net clinical benefit favors the use of more potent P2Y12-receptor inhibitors. For this reason, guidelines-writing authorities assign a class I recommendation for the peri- and post-procedural administration of ticagrelor or prasugrel plus aspirin in patients presenting with STEMI undergoing pPCI [4,5]. More specifically, ticagrelor should be administered after STEMI diagnosis as a loading dose of 180 mg followed by 90 mg twice per day. Prasugrel is recommended as 60 mg loading dose followed by 10 mg once a day. For patients aged ≥75 years or subjects with body weight <60 kg a dose adjustment for prasugrel with a daily dose of 5 mg is mandatory.
Safety and efficacy of P2Y12 inhibitor monotherapy in patients undergoing percutaneous coronary interventions
Published in Expert Opinion on Drug Safety, 2021
Mattia Galli, Davide Capodanno, Felicita Andreotti, Filippo Crea, Dominick J Angiolillo
Finally, the ASET (Aspirin-free prasugrel monotherapy following coronary artery stenting in patients with stable coronary artery disease) [75] pilot study was a multicenter, single-arm study in 201 patients with stable coronary artery disease and low anatomic complexity (mean SYNTAX score 7.2) undergoing PCI with a biodegradable everolimus-eluting platinum chromium DES. Most patients had a single lesion treated with one stent. The use of aspirin was limited to the peri-PCI phase and discontinued after discharge. Prasugrel as a 60 mg loading dose was given immediately post-procedure and maintained 10 mg daily as monotherapy over the ensuing 3 months. Only one patient sustained 2 major adverse events (intracranial hemorrhage followed by cardiac death). Importantly, there were no episodes of definite ST observed over the study period. These pilot data will set the foundation for larger scale clinical investigations.