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Stroke
Published in Henry J. Woodford, Essential Geriatrics, 2022
Clopidogrel (75 mg) has been compared to aspirin (325 mg) in people with vascular disease (n = 19,185; mean age 63; mean follow-up 1.9 years).48 There was a small beneficial effect for the primary outcome of combined ischaemic stroke, MI or vascular death in the clopidogrel group (RR 0.91; 95% 0.83–1.00; 5.3% v 5.8%; NNT = 380 per year). Withdrawal rates were similar. Adverse events seen more commonly with clopidogrel included rash and diarrhoea; those seen with aspirin included upper gastrointestinal (GI) discomfort, and GI and intracranial haemorrhage.
Cardiac Emergencies in Obstetrics
Published in Sanjeewa Padumadasa, Malik Goonewardene, Obstetric Emergencies, 2021
Sanjeewa Padumadasa, Sanjeewa Rajapakse
Low-dose aspirin is safe during pregnancy, but there is limited evidence available regarding the safety of clopidogrel. Beta-blockers can be used, and nifedipine is the drug of choice when coronary spasm is suspected. Newer antiplatelets and statins are contraindicated in pregnancy.
Current outcomes and outcome measures in acute coronary syndrome
Published in K Sarat Chandra, AJ Swamy, Acute Coronary Syndromes, 2020
Dinkar Bhasin, Shaheer Ahmed, Nitish Naik
All patients should receive a loading dose of 162–325 mg of chewable, non-enteric coated aspirin at diagnosis of NSTE-ACS. Dual anti-platelet therapy decreases major adverse cardiovascular events (MACE) and evidence comes from the CURE trial where addition of 300 mg clopidogrel immediately after diagnosis of ACS resulted in a 20% reduction in the hazard ratio for MACE [55]. There was an absolute risk reduction in MACE of 2.1% with an absolute risk increase of 1% of major bleeding with no significant difference in intracranial bleeding or fatal bleeding. This amounts to a net clinical benefit of 1% and hence is the recommended strategy for all patients with ACS (STEMI or NSTEMI). In patients undergoing PCI a total loading dose of 600 mg may further decrease MACE and is the recommended strategy whenever clopidogrel is used. Evidence for this comes from the CURENT OASIS 7 trial where a loading dose of 600 mg followed by 150 mg OD for one week after PCI resulted in lower rates of stent thrombosis [56]. A small but significant percentage of patients with NSTEMI requires CABG. In such patients, a delay of 5 days is suggested after the last dose of clopidogrel.
Decreased platelet miR-199a-5p level might lead to high on-clopidogrel platelet reactivity in patients with coronary artery disease
Published in Platelets, 2023
Xiaolei Hu, Mupeng Li, He Li, Peiyuan Song, Yanjiao Zhang, Gan Zhou, Jie Tang, Liming Peng, Qilin Ma, Xiaoping Chen
Based on the enrichment analysis (KEGG; 3 EM VHTPR vs 10 EM VLTPR) results of the obtained target genes, we found a large number of potential candidate target genes of the differentially expressed miRNAs enriched in the PI3K-Akt signaling pathway which might be activated by βγ subunit of G proteins after P2Y12 receptor stimulation. Activation of the PI3K-Akt signaling pathway leads to the activation of platelet GP IIb/IIIa receptors, which promotes the activation and aggregation of platelets. However, the exact mechanism by which the activated PI3K-Akt pathway regulates the GP IIb/IIIa receptor remains unclear.44 There is evidence indicates that overexpression of active AKT induces rapid downregulation of miR-199a-5p.45,46 Based on our study, the expression of VASP was increased when the expression of miR-199a-5p decreased sharply. Simultaneously, the αi subunit of the G protein released after the activation of the P2Y12 receptor can inhibit the activity of the adenosine cyclase, which results in a reduction in cAMP in platelets. The reduction of cAMP can result in VASP dephosphorylation (conversion of VASP-P to VASP), and then GP IIb/IIIa receptors and platelets were activated in turn. Our study provided a possible mechanism mediating PI3K-Akt to platelet activation. However, further studies are needed to support our hypothesis. Figure 7 gives an overview of the mechanisms of action of clopidogrel according to the previous studies47,48 and our findings.
Are P2Y12 inhibitors superior to aspirin for long-term secondary prevention of cardiovascular disease?
Published in Expert Review of Cardiovascular Therapy, 2023
Stephanie Carlin, John Eikelboom
Aspirin remains the single most widely used antithrombotic treatment for long-term secondary prevention of cardiovascular (CV) disease, including coronary artery disease, peripheral arterial disease, and cerebrovascular disease. A meta-analysis assessing the benefit of aspirin in these populations found a 20% reduction in CV events [1]. Clopidogrel was the first P2Y12 inhibitor to be evaluated as an alternative to aspirin for long-term secondary prevention. In the initial trials, clopidogrel appeared to provide only a small incremental benefit and because it was much more expensive, it was not recommended or widely used for this indication. However, data from more recent randomized controlled trials (RCTs) and meta-analyses suggest that P2Y12 inhibitors are more effective and at least as safe or safer than aspirin. Now that these agents have become generic in most jurisdictions, we believe that P2Y12 inhibitors should become the preferred single agent antiplatelet therapy for long-term secondary prevention.
The role of CYP2C19 genotyping to guide antiplatelet therapy following ischemic stroke or transient ischemic attack
Published in Expert Review of Clinical Pharmacology, 2022
John H McDermott, Marc Leach, Dwaipayan Sen, Craig J. Smith, William G. Newman, Philip M. Bath
Despite efforts from within the pharmacogenetic community, there remains a lack of consensus, and even some conjecture, in relation to prescribing recommendations for clopidogrel based on CYP2C19 status. In 2022, CPIC published their updated guidelines for clopidogrel prescribing based on CYP2C19 genotype [30]. Recommendations for cardiovascular indications were clear, concise, and given with a ‘strong’ classification; clopidogrel should be avoided in intermediate or poor CYP2C19 metabolizers after ACS or PCI. For neurovascular indications, such as IS or TIA, the recommendation was much less definitive. The consensus panel gave a recommendation, with only moderate strength, that in poor or intermediate metabolizers alternative antiplatelets should be considered. Meanwhile the Dutch Pharmacogenetic Working Group (DPWG), another institution who curate pharmacogenetic evidence, have recommend that poor metabolizers should avoid clopidogrel after an IS or TIA [95]. In intermediate metabolizers, a recommendation was made to either avoid clopidogrel or double the dose. The rationale for this recommendation is unclear, though the discrepancy between the two guidelines is likely to be a further symptom of the variable and somewhat contradictory literature identified in this review.