Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention

OBJECTIVES: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). BACKGROUND: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. METHODS: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. RESULTS: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). CONCLUSIONS: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention

OBJECTIVES: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). BACKGROUND: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. METHODS: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. RESULTS: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). CONCLUSIONS: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value

Optimal resting heart rate and ascites‐related death in patients with cirrhosis and ascites using nonselective beta‐blockers (ORCA)

Abstract Nonselective beta‐blockers (NSBBs) may exacerbate ascites by impairing cardiac function. This study evaluated the impact of achieving a heart rate target of 55–60 beats per minute (bpm) on ascites‐related death and complications from worsening ascites in patients with cirrhosis and diuretic‐responsive ascites using NSBBs. A retrospective study was conducted at the Faculty of Medicine Ramathibodi Hospital, Mahidol University (2012–2022) and analyzed patients with cirrhosis and diuretic‐responsive ascites using NSBBs (propranolol/carvedilol) for variceal bleeding prophylaxis. The outcomes were incidence of ascites‐related death and complications from worsening ascites, comparing the achievable target group (heart rate 55–60 bpm) and the unachievable target group (heart rate >60 bpm). A total of 206 patients were included in the study, with a median follow‐up time of 20 months. The patients were divided into an achievable target group (n = 75, median heart rate = 58.0 bpm) and an unachievable target group (n = 131, median heart rate = 73.6 bpm). Propranolol was the most used NSBB (95.1%). The adjusted hazard ratio (HR) for ascites‐related death from spontaneous bacterial peritonitis (SBP) or refractory ascites (RA) or hepatorenal syndrome (HRS) or hepatic encephalopathy (HE) showed no difference between the groups (adjusted HR 0.59 [0.23–1.54]; p = 0.28). Additionally, no significant difference was found in the incidence of complications between groups, including SBP, RA, HRS, and HE. Achieving a heart rate target of 55–60 bpm with NSBBs for variceal bleeding prophylaxis is safe in patients with diuretic‐responsive ascites and cirrhosis

Community pharmacists’ perceived value on precision medicine, desired training components, and exposure during pharmacy education:Malaysia’s experience

Background: Precision medicine beckons new horizons for therapy geared to one’s genetics, lifestyle, and environmental determinants. Molecular, pathology, and clinical diagnostics can be integrated to provide pharmaceutical care. Aims: The value and appeal of precision medicine to community pharmacists, knowledge attained, and training programmes perceived as necessary were evaluated. Methods: Over 10 months, a published questionnaire, which was also digitally accessible during the COVID-19 outbreak, was distributed by hand, via email and social media. 300 community pharmacists across 9 districts in an urban state in Malaysia, self-administered and returned completed versions (response rate 75%). Three- or five-point Likert scale and multiple-choice responses were analysed using SPSS to assess whether or not exposure through the pharmacy curricula impacted current knowledge, perception and willingness to pursue precision medicine. Results: Respondents were largely: females (N = 196, 65.3%) and practicing for up to 10 years (N = 190, 66.3%). Although knowledge levels were moderate (76%), positive perceptions were showcased (94%), and 80% were willing to integrate precision medicine into their daily practice. Although 61% did not or do not recall having had prior exposure to pharmacogenomics as part of their pharmacy school curricula, many (93%) were willing to attain knowledge by undergoing additional training. Desired training included current pharmacogenetic testing available (17%), interpretation of the test results (15%), and ethical considerations (13%). Community pharmacists who had 0.5–10 years’ work experience possessed greater knowledge (μ = 1.48, CI 1.35–1.61, p = 0.017), than the pharmacists who had 21–40 years of work experience (μ = 1.28, CI 1.05–1.51, p = 0.021). Exposure to the subject during pharmacy education positively impacted the willingness to integrate precision medicine in daily practice (p = 0.035). Conclusion: Community pharmacists were receptive to and valued precision medicine. A relatively high number had prior exposure to concepts of precision medicine through the pharmacy curriculum, and were therefore willing to adopt the practice in their day-to-day provision of healthcare. With adequate training centred on bioethics, utilising pharmacogenetic testing, and interpretation of the results, community pharmacists will be equipped for the provision of precision medicine services in the foreseeable future