The Clinical Implementation of CYP2C19 Genotyping in Patients with an Acute Coronary Syndrome:Insights From the FORCE-ACS Registry

BACKGROUND: Guidelines recommend prasugrel or ticagrelor for acute coronary syndrome (ACS) patients. However, these P2Y12 inhibitors increase bleeding risk compared to clopidogrel. Although genotype-guided P2Y12-inhibitor selection has been shown to reduce bleeding risk, data on its clinical implementation is lacking. METHODS: The study included ACS patients receiving genotype-guided antiplatelet therapy, utilising either a point-of-care (POC) device or laboratory-based testing. We aimed to collect qualitative and quantitative data on genotyping, eligibility for de-escalation, physician adherence to genotype results, time to de-escalation and cost reduction. RESULTS: Of the 1,530 patients included in the ACS registry from 2021 to 2023, 738 ACS patients treated with ticagrelor received a CYP2C19 genotype test. The median turnover time of genotyping was 6.3 hours (interquartile range [IQR], 3.2-16.7), with 82.3% of the genotyping results known within 24 hours after admission. POC genotyping exhibited significantly shorter turnaround times compared to laboratory-based testing (with respective medians of 5.7 vs 47.8 hours; P &lt; .001). Of the genotyped patients, 81.7% were eligible for de-escalation which was carried out within 24 hours in 70.9% and within 48 h in 93.0%. The time to de-escalation was significantly shorter using POC (25.4 hours) compared to laboratory-based testing (58.9 hours; P &lt; .001). Implementing this strategy led to a reduction of €211,150.50 in medication costs. CONCLUSIONS: CYP2C19 genotype-guided-de-escalation in an all-comers ACS population is feasible. POC genotyping leads to shorter turnaround times and quicker de-escalation. Time to de-escalation from ticagrelor to clopidogrel in noncarriers was short, with high physician adherence to genotype results.</p

Systematic review of drug effects in humans and models with surfactant-processing disease

Fibrotic interstitial pneumonias are a group of rare diseases characterised by distortion of lung interstitium. Patients with mutations in surfactant-processing genes, such as surfactant protein C (SFTPC), surfactant protein A1 and A2 (SFTPA1 and A2), ATP binding cassette A3 (ABCA3) and Hermansky–Pudlak syndrome (HPS1, 2 and 4), develop progressive pulmonary fibrosis, often culminating in fatal respiratory insufficiency. Although many mutations have been described, little is known about the optimal treatment strategy for fibrotic interstitial pneumonia patients with surfactant-processing mutations. We performed a systematic literature review of studies that described a drug effect in patients, cell or mouse models with a surfactant-processing mutation. In total, 73 articles were selected, consisting of 55 interstitial lung disease case reports/series, two clinical trials and 16 cell or mouse studies. Clinical effect parameters included lung function, radiological characteristics and clinical symptoms, while experimental outcome parameters included chemokine/cytokine expression, surfactant trafficking, necrosis and apoptosis. SP600125, a c-jun N-terminal kinase (JNK) inhibitor, hydroxychloroquine and 4-phenylbutyric acid were most frequently studied in disease models and lead to variable outcomes, suggesting that outcome is mutation dependent. This systematic review summarises effect parameters for future studies on surfactant-processing disorders in disease models and provides directions for future trials in affected patients

Unintentional guideline deviations in hospitalized patients with two or more antithrombotic agents:an intervention study

Purpose Treatment schedules for antithrombotic therapy are complex, and there is a risk of inappropriate prescribing or continuation of antithrombotic therapy beyond the intended period of time. The primary aim of this study was to determine the frequency of unintentional guideline deviations in hospitalized patients. Secondary aims were to determine whether the frequency of unintentional guideline deviations decreased after intervention by a pharmacist, to determine the acceptance rate of the interventions and to determine the type of interventions. Methods We performed a non-controlled prospective intervention study in three teaching hospitals in the Netherlands. We examined whether hospitalized patients who used the combination of an anticoagulant plus at least one other antithrombotic agent had an unintentional guideline deviation. In these cases, the hospital pharmacist contacted the physician to assess whether this deviation was intentional. If the deviation was unintentional, a recommendation was provided how to adjust the antithrombotic regimen according to guideline recommendations. Results Of the 988 included patients, 407 patients had an unintentional guideline deviation (41.2%). After intervention, this was reduced to 22 patients (2.2%) (p < 0.001). The acceptance rate of the interventions was 96.6%. The most frequently performed interventions were discontinuation of an low molecular weight heparin in combination with a direct oral anticoagulant and discontinuation of an antiplatelet agent when there was no indication for the combination of an antiplatelet agent and an anticoagulant. Conclusion A significant number of hospitalized patients who used an anticoagulant plus one other antithrombotic agent had an unintentional guideline deviation. Intervention by a pharmacist decreased unintentional guideline deviations

Subdivision of aspirin tablets? Use your hands: a study on aspirin tablet subdivision using four different methods

Background/Aim: Low-dose aspirin therapy (1 × 75–150 mg) is used in the secondary prevention of cardiovascular diseases. Recently it has been suggested that a twice daily regimen is more effective (2 × 40–75 mg). We therefore compared the precision of four subdivision methods. Method: A total of 280 aspirin tablets (acetylsalicylic acid 80 mg) were subdivided using four different methods (PillTool, hand, knife and Pilomat). Precision was compared using a difference score and loss of mass. The accuracy (uniformity of weight) was evaluated according to an adapted version of the European Pharmacopoeia test. Loss of mass was analysed using the criteria of the US Food and Drug Administration. Results: Evaluating the difference score (mean ± SD: PillTool 22 ± 14; hand 14 ± 8; knife 36 ± 23; and Pilomat 20 ± 13), the knife method was less precise than the PillTool, the hand method and the Pilomat (for all p < 0.001). Furthermore, the hand (p < 0.001) and the PillTool (p < 0.001) had statistically significantly a smaller loss of mass (mg) than the knife and the Pilomat (median (interquartile range): PillTool 1 (2), hand 0 (2), knife 4 (6) and Pilomat 3 (5)). Only breaking by hand complied with the adapted European Pharmacopoeia test. Tablets broken by PillTool and hand fulfilled the criteria of the US Food and Drug Administration test for loss of mass. Conclusion: Based on the results of our study, we recommend hand breaking and to avoid a knife for the best weight uniform tablets. If a tablet splitting device is necessary we advise use of the PillTool