Stent thrombosis and restenosis
Ever D. Grech in Practical Interventional Cardiology, 2017
Prasugrel is a thienopyridine that was developed to more quickly and effectively inhibit platelets than clopidogrel. Its use was validated in the TRITON trial, a trial which randomised 13,608 patients with moderate- to high-risk acute coronary syndromes undergoing PCI to 6–15 months of dual anti-platelets therapy. In this trial, prasugrel significantly reduced the rate of stent thrombosis as compared with clopidogrel (1.1% vs. 2.4%, p < .001) at the cost of increasing the rate of non-CABG related TIMI major bleeding (p = .03), major or minor bleeding (p = .002). Additionally, prasugrel increased mortality in patients with a prior stroke, and as such should not be given to patients with a history of transient ischemic attack or stroke.17
Antiplatelet therapy in interventional cardiology
John Edward Boland, David W. M. Muller in 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.
Acute coronary syndromes
Henry J. Woodford in 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.
Sickle cell disease as a vascular disorder
Published in Expert Review of Hematology, 2020
Because platelets may be involved in intercellular adhesion, inflammatory processes, and thrombosis during VOCs, anti-platelet agents have also been under investigation for reducing VOCs in SCD [81]. Prasugrel, a third-generation thienopyridine that irreversibly inhibits ADP-mediated platelet activation and aggregation, is currently indicated for the treatment of adults with acute coronary syndrome managed with percutaneous coronary intervention. The DOVE trial, a phase 3, double-blind, placebo-controlled study of children with SCD, investigated prasugrel for the prevention of VOCs [81,82]. Children 2–17 years of age who had at least two VOCs in the previous year were randomly assigned to receive oral prasugrel (n = 171) or placebo (n = 170) for 9–24 months. Although there was a trend for the rate of VOCs to be lower among those who received prasugrel (67.3%) compared with those receiving placebo (72.4%), the difference was not statistically significant. Prasugrel also had no significant impact on secondary endpoints, including sickle cell-related pain and intensity of pain during VOCs. There appeared to be a greater reduction in VOCs among patients 12–17 years old and in patients not receiving hydroxyurea, but these were also not significant [82]. Although the results of this trial were somewhat disappointing, inhibition of platelet activation and aggregation remains of interest in the reduction of VOCs and should be pursued further.
A noninferiority confirmatory trial of prasugrel versus clopidogrel in Japanese patients with non-cardioembolic stroke: rationale and study design for a randomized controlled trial – PRASTRO-I trial
Published in Expert Opinion on Pharmacotherapy, 2018
Takehiko Nagao, Kazunori Toyoda, Kazuo Kitagawa, Takanari Kitazono, Hiroshi Yamagami, Shinichiro Uchiyama, Norio Tanahashi, Masayasu Matsumoto, Kazuo Minematsu, Izumi Nagata, Masakatsu Nishikawa, Shinsuke Nanto, Kenji Abe, Yasuo Ikeda, Akira Ogawa
Prasugrel is a thienopyridine antiplatelet agent and adenosine diphosphate (ADP) receptor antagonist. The active metabolite of prasugrel selectively inhibits the P2Y12 receptor located on the platelet membrane, thereby suppressing platelet aggregation. Nonclinical and clinical trials conducted to date have indicated that prasugrel inhibits platelet aggregation more potently, exerts therapeutic action faster, and is less influenced by CYP2C19 polymorphisms than clopidogrel sulfate. In the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38), prasugrel (loading/maintenance doses: 60/10 mg) reduced the rates of ischemic events (a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) significantly more than clopidogrel sulfate in patients who had undergone percutaneous coronary intervention (PCI) for the treatment of acute coronary syndrome and were concomitantly administered aspirin [16]. Of note is that prasugrel suppressed ischemic events effectively in the subgroup of patients with diabetes as well as in CYP2C19 PM and IM patients [17,18]. Based on those results, prasugrel has gained regulatory approval in the US and European countries for the treatment of acute coronary syndrome in patients undergoing PCI. However, patients with a history of stroke may have an increased frequency of developing bleeding complications, such as intracranial hemorrhage. Therefore, we considered that lower doses of prasugrel could diminish the risk of bleeding in stroke patients.
Pharmacologic considerations in the management of acute coronary syndrome in elderly patients
Published in Expert Opinion on Pharmacotherapy, 2019
Brandon K. Martinez, C. Michael White
In a substudy of the PLATelet inhibition and patient Outcomes (PLATO) trial, ticagrelor was shown to maintain the significant clinical benefit without an increased risk of major bleeding compared to clopidogrel in patients >75 years of age [12]. Prasugrel contains a black box warning for the use in patients ≥75 years of age and in patients < 60 kg due to a higher risk of bleeding. However, prasugrel may have efficacy advantages in patients with diabetes or prior myocardial infarction that are more common in the elderly. The European Medicines Agency approved a 5 mg daily dose of prasugrel for patients ≥ 75 years of age. This is based largely on a pharmacokinetic substudy of the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction (TRITON–TIMI) 38, which showed a significantly higher concentration of the active metabolite in patients ≥ 75 years old [13]. Clopidogrel is the only P2Y12 inhibitor recommended in the setting of concomitant fibrinolytic use but patients ≥ 75 years should not receive the loading dose [5].
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- Stent
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- St Elevation