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The ABCD‐GENE score was developed to predict poor response to clopidogrel and includes Age, Body mass index, Chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2), Diabetes, and CYP2C19 GENE variants; a score ≥ 10 is predictive of reduced clopidogrel effectiveness after percutaneous coronary intervention (PCI). Estimation of GFR without a race variable via the CKD‐EPI Scr 2021 equation is now recommended. We examined the impact of using the CKD‐EPI Scr 2021 vs. 2009 equation on the ABCD‐GENE score for post‐PCI patients. A total of 4335 adult patients (n = 925 Black) who underwent PCI and CYP2C19 genotyping were included, with GFR estimated for each patient via the CKD‐EPI Scr 2021 and CKD‐EPI 2009 equations. The ABCD‐GENE score, calculated based on each GFR estimation, was compared. With the CKD‐EPI Scr 2021 vs. 2009 equation, median (IQR) eGFR was lower (74 [55–94] vs. 81 [60–103] mL/min/1.73 m2, P < 0.001), and CKD prevalence was higher (31% vs. 25%, P < 0.001) among Black patients, whereas eGFR was higher (85 [65–99] vs. 80 [61–94] mL/min/1.73m2, P < 0.001), and CKD prevalence was lower (20% vs. 24%, P < 0.001) in non‐Black patients. This led to 12 (1%) Black patients being reclassified from low to high risk of poor clopidogrel response and 30 (1%) non‐Black patients being recategorized from high to low risk (P < 0.001 for both comparisons). Removal of the race variable from GFR estimation significantly impacted the prediction of clopidogrel effectiveness via the ABCD‐GENE score. [ABSTRACT FROM AUTHOR]

Over the past decades, there have been great advancements in the antithrombotic management of patients undergoing percutaneous interventions, but most of the available evidence derives from studies conducted in the setting of cardiac interventions. Antithrombotic treatment regimens used in patients undergoing percutaneous cardiac interventions, in particular coronary, are frequently extrapolated to patients undergoing noncardiac interventions. However, the differences in risk profile of the population treated and the types of interventions performed may translate into differences is the safety and efficacy associated with antithrombotic therapy. Noncardiac percutaneous interventions are commonly performed in patients at high bleeding risk, which may indeed impact outcomes, hence underscoring the importance of risk stratification to guide clinical decision-making processes. In this review, we appraise the available evidence on antithrombotic therapy in high-bleeding-risk patients undergoing noncardiac percutaneous interventions. [Display omitted] [Display omitted] • There is a paucity of evidence on the optimal antithrombotic treatment regimen to be used in patients undergoing noncardiac percutaneous interventions. Antithrombotic strategies in this setting often empirically reflect that from patients undergoing percutaneous coronary interventions. Similarly, evidence on the incidence and prognostic impact of bleeding as well as on HBR classifications is scarce compared with the coronary setting. • Patients undergoing noncardiac interventions are often characterized by an increased risk of bleeding. In fact, these procedures are often reserved for patients with prohibitively high surgical and bleeding risks (eg, advanced age, multiple comorbidities). Moreover, there are differences in the thrombogenicity of the devices used and in the safety and efficacy of specific antithrombotic regimens between cardiac and noncardiac interventions. • In this review, we discuss definitions and clinical impact of HBR in patients undergoing noncardiac percutaneous interventions and the implications for antithrombotic treatment regimens in this population. [ABSTRACT FROM AUTHOR]

Little is known about the use of cangrelor in patients with myocardial infarction (MI) presenting with cardiogenic shock (CS). CAMEO (Cangrelor in Acute MI: Effectiveness and Outcomes) is a multicenter observational registry evaluating platelet inhibition in patients with MI. We examined the duration of cangrelor infusion and the amount of time to transition from cangrelor to an oral P2Y 12 inhibitor in patients with CS. We also assessed major adverse cardiovascular events (MACEs) and bleeding risks, stratified by dosage duration, time to transition and oral P2Y 12 inhibitor potency. Among 2352 cangrelor-treated patients with MI, 249 patients were in CS. Among the patients with CS, 16 (6.4%) received the "bridge" infusion dose, 202 (81.1%) the PCI cangrelor infusion dose, and 30 (12.0%) had a combination of both infusion doses. Patients with CS had a median age of 66 years; 32% were women; 21% were Black patients; 35% had diabetes; 19% received thrombectomy; and 59% received mechanical circulatory support (MCS) (35% intra-aortic balloon pump, 27% Impella). The median duration of infusion was 3.9 (2–21.5 hours) in patients with CS and was 2 (1.6–3.1 hours) for all cangrelor-treated patients. The median duration of transition from cangrelor to oral P2Y 12 inhibitor administration was 0.1 (-0.5–21.0 hours) for patients with CS. In multivariable modeling, chronic lung disease and the use of MCS and was associated with longer cangrelor infusions (defined as > 3.9 hours). Among cangrelor-treated patients with CS, 24.1% of these patients had a bleeding event, and 41.8% had a MACE event. After adjustment, a longer cangrelor infusion duration was associated with increased risk of bleeding (P < 0.05). The median duration of cangrelor infusion was longer for patients presenting with CS. Use of MCS was associated with longer cangrelor infusion durations in patients with CS. Further work is needed to understand the pharmacodynamics of antiplatelet agents in patients with CS. [ABSTRACT FROM AUTHOR]

Background and Aims Patients with high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI) are at increased risk of not only bleeding, but also ischaemic events. This study aimed to determine the long-term relative risk of ischaemic and bleeding events in HBR patients. Methods This study was a nationwide cohort study, based on the Korean National Health Insurance Review and Assessment Service database. Patients diagnosed with stable angina or acute coronary syndrome and those who underwent PCI in Korea between 2009 and 2018 were included in the analysis. According to the Academic Research Consortium HBR criteria, the total population was divided into HBR and non-HBR groups. The co-primary outcomes were major bleeding events and ischaemic (composite of cardiac death, myocardial infarction, and ischaemic stroke) events. Results Among a total of 325 417 patients who underwent PCI, 66 426 patients (20.4%) had HBR. During the follow-up period, HBR patients had a higher risk for major bleeding events (23.9% vs. 8.9%, P <.001) and ischaemic events (33.8% vs. 14.4%, P <.001). However, the impact of HBR was significant for major bleeding events [hazard ratio (HR) 3.12, 95% confidence interval (CI) 3.04–3.21, P <.001] and for ischaemic events (HR 2.50, 95% CI 2.45–2.56, P <.001). The HBR group was also associated with a greater risk of all-cause mortality (HR 3.73, 95% CI 3.66–3.79, P <.001). The average annual rate of major bleeding events within the first year after PCI was 5.5% for a single major criterion, and 2.9% for a single minor criterion. Conclusions Among patients undergoing PCI, those with HBR were at increased long-term risk for both bleeding and ischaemic events, with a greater risk of mortality compared to non-HBR patients. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection.Significance: New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. Cancer Discov; 8(9); 1112-29. ©2018 AACR.See related commentary by Collisson, p. 1062This article is highlighted in the In This Issue feature, p. 1047.