De-escalation to ticagrelor monotherapy versus 12 months of dual antiplatelet therapy in patients with and without acute coronary syndromes: a systematic review and individual patient-level meta-analysis of randomised trials.

BACKGROUND: Dual antiplatelet therapy (DAPT) for 12 months is the standard of care after coronary stenting in patients with acute coronary syndrome (ACS). The aim of this individual patient-level meta-analysis was to summarise the evidence comparing DAPT de-escalation to ticagrelor monotherapy versus continuing DAPT for 12 months after coronary drug-eluting stent implantation. METHODS: A systematic review and individual patient data (IPD)-level meta-analysis of randomised trials with centrally adjudicated endpoints was performed to evaluate the comparative efficacy and safety of ticagrelor monotherapy (90 mg twice a day) after short-term DAPT (from 2 weeks to 3 months) versus 12-month DAPT in patients undergoing percutaneous coronary intervention with a coronary drug-eluting stent. Randomised trials comparing P2Y12 inhibitor monotherapy with DAPT after coronary revascularisation were searched in Ovid MEDLINE, Embase, and two websites (www.tctmd.com and www.escardio.org) from database inception up to May 20, 2024. Trials that included patients with an indication for long-term oral anticoagulants were excluded. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. The principal investigators of the eligible trials provided IPD by means of an anonymised electronic dataset. The three ranked coprimary endpoints were major adverse cardiovascular or cerebrovascular events (MACCE; a composite of all-cause death, myocardial infarction, or stroke) tested for non-inferiority in the per-protocol population; and Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding and all-cause death tested for superiority in the intention-to-treat population. All outcomes are reported as Kaplan-Meier estimates. The non-inferiority was tested using a one-sided α of 0·025 with the prespecified non-inferiority margin of 1·15 (hazard ratio [HR] scale), followed by the ranked superiority testing at a two-sided α of 0·05. This study is registered with PROSPERO (CRD42024506083). FINDINGS: A total of 8361 unique citations were screened, of which 610 records were considered potentially eligible during the screening of titles and abstracts. Of these, six trials that randomly assigned patients to ticagrelor monotherapy or DAPT were identified. De-escalation took place a median of 78 days (IQR 31-92) after intervention, with a median duration of treatment of 334 days (329-365). Among 23 256 patients in the per-protocol population, MACCE occurred in 297 (Kaplan-Meier estimate 2·8%) with ticagrelor monotherapy and 332 (Kaplan-Meier estimate 3·2%) with DAPT (HR 0·91 [95% CI 0·78-1·07]; p=0·0039 for non-inferiority; τ2<0·0001). Among 24 407 patients in the intention-to-treat population, the risks of BARC 3 or 5 bleeding (Kaplan-Meier estimate 0·9% vs 2·1%; HR 0·43 [95% CI 0·34-0·54]; p<0·0001 for superiority; τ2=0·079) and all-cause death (Kaplan-Meier estimate 0·9% vs 1·2%; 0·76 [0·59-0·98]; p=0·034 for superiority; τ2<0·0001) were lower with ticagrelor monotherapy. Trial sequential analysis showed strong evidence of non-inferiority for MACCE and superiority for bleeding among the overall and ACS populations (the z-curve crossed the monitoring boundaries or the required information size without crossing the futility boundaries or approaching the null). The treatment effects were heterogeneous by sex for MACCE (p interaction=0·041) and all-cause death (p interaction=0·050), indicating a possible benefit in women with ticagrelor monotherapy, and by clinical presentation for bleeding (p interaction=0·022), indicating a benefit in ACS with ticagrelor monotherapy. INTERPRETATION: Our study found robust evidence that, compared with 12 months of DAPT, de-escalation to ticagrelor monotherapy does not increase ischaemic risk and reduces the risk of major bleeding, especially in patients with ACS. Ticagrelor monotherapy might also be associated with a mortality benefit, particularly among women, which warrants further investigation. FUNDING: Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale.

Clopidogrel-Mediated P2Y12 Inhibition According to Renal Function in Patients With Diabetes Mellitus and CAD.

This prospective ex vivo and in vitro pharmacodynamic (PD)/pharmacokinetic investigation was conducted in patients with diabetes mellitus with (n = 31) and without chronic kidney disease (n = 30). PD assessments included platelet reactivity index, maximum platelet aggregation, and P2Y12 reaction units. Ex vivo pharmacokinetic assessments included plasma levels of clopidogrel and its active metabolite. In vitro PD assessments were conducted on baseline samples incubated with escalating concentrations of clopidogrel and its active metabolite. Among patients with diabetes mellitus treated with clopidogrel, impaired renal function was associated with increased maximum platelet aggregation. This finding could be attributed partially to upregulation of the P2Y12 activity without differences in drug absorption or metabolism. (Impact of Chronic Kidney Disease on Clopidogrel Effects in Diabetes Mellitus; NCT03774394).

Risk of Bleeding Among Cangrelor-Treated Patients Administered Upstream P2Y12 Inhibitor Therapy: The CAMEO Registry.

Background: Little is known about the bleeding risk associated with cangrelor use in patients with myocardial infarction (MI) who are exposed to an oral P2Y12 inhibitor before coronary angiography. Methods: Cangrelor in Acute MI: Effectiveness and Outcomes (CAMEO) is an observational registry studying platelet inhibition for patients with MI. Upstream oral P2Y12 inhibition was defined as receipt of an oral P2Y12 inhibitor within 24 hours before hospitalization or in-hospital before angiography. Among cangrelor-treated patients, we compared bleeding after cangrelor use through 7 days postdischarge between patients with and without upstream oral P2Y12 inhibitor exposure. Results: Among 1802 cangrelor-treated patients with MI, 385 (21.4%) received upstream oral P2Y12 inhibitor treatment. Of these, 101 patients (33.8%) started cangrelor within 1 hour, 103 (34.4%) between 1 and 3 hours, and 95 (31.8%), >3 hours after in-hospital oral P2Y12 inhibitor administration; the remaining received an oral P2Y12 inhibitor before hospitalization. There was no statistically significant difference in rates of bleeding among cangrelor-treated patients with and without upstream oral P2Y12 inhibitor exposure (6.5% vs 8.8%; adjusted odds ratio [OR], 0.62; 95% CI, 0.38-1.01). Bleeding was observed in 5.0%, 10.7%, and 3.2% of patients treated with cangrelor <1, 1 to 3, and >3 hours after the last oral PY12 inhibitor dose, respectively; bleeding rates were not statistically different between groups (1-3 hours vs <1 hour: adjusted OR, 2.70; 95% CI, 0.87-8.32; >3 hours vs <1 hour: adjusted OR, 0.65; 95% CI, 0.15-2.85). Conclusions: Bleeding risk was not observed to be significantly higher after cangrelor treatment in patients with and without upstream oral P2Y12 inhibitor exposure.

Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry - Informing optimal antiplatelet strategies.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no-function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no-function allele carriers. However, the influence of patient-specific demographic, clinical, and other genetic factors on outcomes with genotype-guided DAPT has not been defined. In addition, the impact of genotype-guided de-escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no-function allele has not been investigated in a diverse, real-world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient-specific factors on clinical outcomes with CYP2C19-guided DAPT, evaluate the safety and effectiveness of CYP2C19-guided DAPT de-escalation following PCI in a real-world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real-world population.

Five-Feature Models to Predict Preeclampsia Onset Time From Electronic Health Record Data: Development and Validation Study.

BACKGROUND:  Preeclampsia is a potentially fatal complication during pregnancy, characterized by high blood pressure and the presence of excessive proteins in the urine. Due to its complexity, the prediction of preeclampsia onset is often difficult and inaccurate. OBJECTIVE:  This study aimed to create quantitative models to predict the onset gestational age of preeclampsia using electronic health records. METHODS:  We retrospectively collected 1178 preeclamptic pregnancy records from the University of Michigan Health System as the discovery cohort, and 881 records from the University of Florida Health System as the validation cohort. We constructed 2 Cox-proportional hazards models: 1 baseline model using maternal and pregnancy characteristics, and the other full model with additional laboratory findings, vitals, and medications. We built the models using 80% of the discovery data, tested the remaining 20% of the discovery data, and validated with the University of Florida data. We further stratified the patients into high- and low-risk groups for preeclampsia onset risk assessment. RESULTS:  The baseline model reached Concordance indices of 0.64 and 0.61 in the 20% testing data and the validation data, respectively, while the full model increased these Concordance indices to 0.69 and 0.61, respectively. For preeclampsia diagnosed at 34 weeks, the baseline and full models had area under the curve (AUC) values of 0.65 and 0.70, and AUC values of 0.69 and 0.70 for preeclampsia diagnosed at 37 weeks, respectively. Both models contain 5 selective features, among which the number of fetuses in the pregnancy, hypertension, and parity are shared between the 2 models with similar hazard ratios and significant P values. In the full model, maximum diastolic blood pressure in early pregnancy was the predominant feature. CONCLUSIONS:  Electronic health records data provide useful information to predict the gestational age of preeclampsia onset. Stratification of the cohorts using 5-predictor Cox-proportional hazards models provides clinicians with convenient tools to assess the onset time of preeclampsia in patients.

Antithrombotic therapy for transcatheter structural heart intervention.

Percutaneous transcatheter structural heart interventions have considerably expanded within the last two decades, improving clinical outcomes and quality of life versus guideline-directed medical therapy for patients frequently ineligible for surgical treatment. Transcatheter structural heart interventions comprise valve implantation or repair and also occlusions of the patent foramen ovale, atrial septal defects and left atrial appendage. These procedures expose structural devices to arterial or venous blood flow with various rheological conditions leading to potential thrombotic complications and embolisation. Furthermore, these procedures may concern comorbid patients at high risk of both ischaemic and bleeding complications. This state-of-the-art review provides a description of the device-related thrombotic risk associated with these transcatheter structural heart interventions and of the current evidence-based guidelines regarding antithrombotic treatments. Gaps in evidence for each of the studied transcatheter interventions and the main ongoing trials are also summarised.

Long-term outcomes of high bleeding risk patients undergoing percutaneous coronary intervention: a Korean nationwide registry.

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.

Demystifying the Contemporary Role of 12-Month Dual Antiplatelet Therapy After Acute Coronary Syndrome.

For almost two decades, 12-month dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) has been the only class I recommendation on DAPT in American and European guidelines, which has resulted in 12-month durations of DAPT therapy being the most frequently implemented in ACS patients undergoing percutaneous coronary intervention (PCI) across the globe. Twelve-month DAPT was initially grounded in the results of the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial, which, by design, studied DAPT versus no DAPT rather than the optimal DAPT duration. The average DAPT duration in this study was 9 months, not 12 months. Subsequent ACS studies, which were not designed to assess DAPT duration, rather its composition (aspirin with prasugrel or ticagrelor compared with clopidogrel) were further interpreted as supportive evidence for 12-month DAPT duration. In these studies, the median DAPT duration was 9 or 15 months for ticagrelor and prasugrel, respectively. Several subsequent studies questioned the 12-month regimen and suggested that DAPT duration should either be fewer than 12 months in patients at high bleeding risk or more than 12 months in patients at high ischemic risk who can safely tolerate the treatment. Bleeding, rather than ischemic risk assessment, has emerged as a treatment modifier for maximizing the net clinical benefit of DAPT, due to excessive bleeding and no clear benefit of prolonged treatment regimens in high bleeding risk patients. Multiple DAPT de-escalation treatment strategies, including switching from prasugrel or ticagrelor to clopidogrel, reducing the dose of prasugrel or ticagrelor, and shortening DAPT duration while maintaining monotherapy with ticagrelor, have been consistently shown to reduce bleeding without increasing fatal or nonfatal cardiovascular or cerebral ischemic risks compared with 12-month DAPT. However, 12-month DAPT remains the only class-I DAPT recommendation for patients with ACS despite the lack of prospectively established evidence, leading to unnecessary and potentially harmful overtreatment in many patients. It is time for clinical practice and guideline recommendations to be updated to reflect the totality of the evidence regarding the optimal DAPT duration in ACS.

The pharmacology of antiplatelet agents for primary, secondary, and tertiary prevention of ischemic stroke.

INTRODUCTION: Ischemic etiology accounts for two thirds of all strokes in which platelet activation and aggregation play a major role. A variety of antiplatelet therapies have been tested for primary, secondary, and tertiary prevention, with certain patient subtypes benefiting more than others from a specific regimen. AREAS COVERED: This review aims at synthetizing current evidence on pharmacology of antiplatelet agents approved for primary, secondary, and tertiary stroke prevention and their application among possible patient subtypes that may benefit more from their administration. EXPERT OPINION: Management of ischemic stroke has largely evolved over the past decades. A better understanding of stroke pathophysiology has allowed to identify patients who can benefit most from antiplatelet therapies, with varying degrees of benefit depending on whether these agents are being used for primary, secondary, or tertiary prevention. Importantly, the antiplatelet treatment regimens currently available have expanded and no longer limited to aspirin but include other drugs such as P2Y12 and phosphodiesterase inhibitors, also used in combination, as well as precision medicine approaches using genetic testing aiming at optimizing the safety and efficacy in this population.

Therapeutic Potential of FXI Inhibitors: Hype or Hope?

Significant advancements have shaped the landscape of anticoagulant therapy in the past two decades, including the introduction of direct oral anticoagulants (DOACs), characterized by favorable safety and efficacy profiles and reduced drug-to-drug or food interaction resulting in excellent patient compliance. However, residual concerns still exist with standard-of-care anticoagulant therapy, including the inability to use DOACs in several clinical settings and the need to further reduce the risk of bleeding. Recent improvements in the understanding of the mechanisms behind thrombus formation have led to the awareness that the intrinsic pathway of the coagulation cascade may play an important role in pathological thrombosis, but not in hemostasis. This has represented the rationale for targeting this pathway with factor XI (FXI) inhibitors, with the aim of uncoupling hemostasis and thrombosis. Clinical evidence from patients with FXI deficiency further supports this concept. A number of compounds with different mechanisms of action have been developed to target FXI (i.e., asundexian, abelacimab, Ionis-FXIRx, milvexian, osocimab, and Xisomab 3G). To date, the majority of available trials have not gone beyond completion of phase 2 and results are conflictive making it difficult to appraise the clinical benefit of these compounds in the different clinical settings where they have been tested (i.e., atrial fibrillation, acute ischemic stroke, acute myocardial infarction, end-stage renal disease, total knee arthroplasty). Moreover, the largest phase 3 randomized trial designed to test the efficacy of asundexian over apixaban in patients with atrial fibrillation, the OCEANIC-AF, has been prematurely stopped as a result of the inferior efficacy of asundexian. In this review we discuss the pharmacological properties and available evidence generated thus far for factor XI inhibitors, providing a perspective on the current state of these drugs.

Evaluating the Effect of Estimating Renal Function With the CKD-EPI 2021 Equation on the ABCD-GENE Score for Clopidogrel Response Prediction.

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.

P2Y12 Inhibitor Monotherapy After Short DAPT in Acute Coronary Syndrome: A Systematic Review and Meta-analysis.

BACKGROUND: P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) may balance ischemic and bleeding risks in patients with acute coronary syndrome (ACS). However, it remains uncertain how different P2Y12 inhibitors used as monotherapy affect outcomes. METHODS: Randomized controlled trials comparing P2Y12 inhibitor monotherapy after a short course of DAPT (≤3 months) versus 12-month DAPT in ACS were included. The primary endpoint was major adverse cardiovascular events (MACE). All analyses included an interaction term for the P2Y12 inhibitor used as monotherapy. Trial sequential analysis were run to explore whether the effect estimate of each outcomes may be affected by further studies. RESULTS: Seven trials encompassing 27,284 ACS patients were included. Compared with 12-month DAPT, P2Y12 inhibitor monotherapy after a short course of DAPT was associated with no difference in MACE (OR 0.92, 95% CI 0.76-1.12) and a significant reduction in net adverse clinical events (NACE) (OR 0.75; 95% CI 0.60-0.94), any bleeding (OR 0.54, 95% CI 0.43-0.66) and major bleeding (OR 0.47, 95% CI 0.37-0.60). Significant interactions for subgroup difference between ticagrelor and clopidogrel monotherapy were found for MACE (pint=0.016), all-cause death (pint=0.042), NACE (pint=0.018), and myocardial infarction (pint=0.028). Trial sequential analysis showed conclusive evidence of improved NACE with ticagrelor, but not with clopidogrel monotherapy, compared with standard DAPT. CONCLUSIONS: In patients with ACS, P2Y12 inhibitor monotherapy after short DAPT halves bleeding without increasing ischemic events compared with standard DAPT. Ticagrelor, but not clopidogrel monotherapy, reduced MACE, NACE and mortality compared with standard DAPT, supporting its use after aspirin discontinuation. Protocol registration: This study is registered in PROSPERO (CRD42023494797).

Temporary omission of oral anticoagulation in atrial fibrillation patients undergoing percutaneous coronary intervention: rationale and design of the WOEST-3 randomised trial.

The optimal antithrombotic management of atrial fibrillation (AF) patients who require oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) remains unclear. Current guidelines recommend dual antithrombotic therapy (DAT; OAC plus P2Y12 inhibitor - preferably clopidogrel) after a short course of triple antithrombotic therapy (TAT; DAT plus aspirin). Although DAT reduces bleeding risk compared to TAT, this is counterbalanced by an increase in ischaemic events. Aspirin provides early ischaemic benefit, but TAT is associated with an increased haemorrhagic burden; therefore, we propose a 30-day dual antiplatelet therapy (DAPT; aspirin plus P2Y12 inhibitor) strategy post-PCI, temporarily omitting OAC. The study aims to compare bleeding and ischaemic risk between a 30-day DAPT strategy following PCI and a guideline-directed therapy in AF patients requiring OAC. WOEST-3 (ClinicalTrials.gov: NCT04436978) is an investigator-initiated, international, open-label, randomised controlled trial (RCT). AF patients requiring OAC who have undergone successful PCI will be randomised within 72 hours after PCI to guideline-directed therapy (edoxaban plus P2Y12 inhibitor plus limited duration of aspirin) or a 30-day DAPT strategy (P2Y12 inhibitor plus aspirin, immediately discontinuing OAC) followed by DAT (edoxaban plus P2Y12 inhibitor). With a sample size of 2,000 patients, this trial is powered to assess both superiority for major or clinically relevant non-major bleeding and non-inferiority for a composite of all-cause death, myocardial infarction, stroke, systemic embolism or stent thrombosis. In summary, the WOEST-3 trial is the first RCT temporarily omitting OAC in AF patients, comparing a 30-day DAPT strategy with guideline-directed therapy post-PCI to reduce bleeding events without hampering efficacy.

Gender Diversity Among Reconstructive Microsurgery Studies Based on the Relative Citation Ratio: An 18-Year Analysis.

BACKGROUND: Gender disparities in plastic surgery authorship have been previously described in the literature. The relative citation ratio (RCR) index is a new metric that normalizes citation rates for field and time, which can be utilized to compare authors. This study aims to evaluate differences in gender authorship in reconstructive microsurgery (RM) papers, as well as the impact of gender on the RCR index. METHODS: A PubMed query isolated RM studies between 2002 and 2020 across the 3 highest impact PS journals. Author names and RCR information were collected from NIH iCite. The likely gender was adjudicated by using NamSor-Software. Unpaired Wilcoxon rank-sum and chi-square tests were used to assess differences between groups. RESULTS: Of 1146 articles (2172 authors), there was a significant difference between the proportion of females as senior authors compared to first authors (P < 0.001). Overall, females represented 15.4% of all authors, 19.7% of first authors, and 11.3% of senior authors. Males had a significantly higher weighted RCR (P < 0.0001) and number of publications (P < 0.0001), which remained significant when stratified by first and senior author. Female authors collectively had a higher mean RCR (P = 0.008) and among first authors (P < 0.0001), with no significant difference among senior authors (P = 0.47). CONCLUSION: A considerably greater number of males are publishing in reconstructive microsurgery compared to females, with significantly more males being senior authors compared to first authors. Males had higher weighted RCR scores and publications compared to females. This study suggests that equity in gender authorship within the field is yet to be achieved.

Systematic data quality assessment of electronic health record data to evaluate study-specific fitness: Report from the PRESERVE research study.

Study-specific data quality testing is an essential part of minimizing analytic errors, particularly for studies making secondary use of clinical data. We applied a systematic and reproducible approach for study-specific data quality testing to the analysis plan for PRESERVE, a 15-site, EHR-based observational study of chronic kidney disease in children. This approach integrated widely adopted data quality concepts with healthcare-specific evaluation methods. We implemented two rounds of data quality assessment. The first produced high-level evaluation using aggregate results from a distributed query, focused on cohort identification and main analytic requirements. The second focused on extended testing of row-level data centralized for analysis. We systematized reporting and cataloguing of data quality issues, providing institutional teams with prioritized issues for resolution. We tracked improvements and documented anomalous data for consideration during analyses. The checks we developed identified 115 and 157 data quality issues in the two rounds, involving completeness, data model conformance, cross-variable concordance, consistency, and plausibility, extending traditional data quality approaches to address more complex stratification and temporal patterns. Resolution efforts focused on higher priority issues, given finite study resources. In many cases, institutional teams were able to correct data extraction errors or obtain additional data, avoiding exclusion of 2 institutions entirely and resolving 123 other gaps. Other results identified complexities in measures of kidney function, bearing on the study's outcome definition. Where limitations such as these are intrinsic to clinical data, the study team must account for them in conducting analyses. This study rigorously evaluated fitness of data for intended use. The framework is reusable and built on a strong theoretical underpinning. Significant data quality issues that would have otherwise delayed analyses or made data unusable were addressed. This study highlights the need for teams combining subject-matter and informatics expertise to address data quality when working with real world data.

CYP2C19 Genotype Is Associated With Adverse Cardiovascular Outcomes in Black Patients Treated With Clopidogrel Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear. METHODS AND RESULTS: Adults among 5 institutions who self-identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P<0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel-treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person-years; adjusted hazard ratio, 2.00 [95% CI, 1.20-3.33], P=0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups. CONCLUSIONS: Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real-world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype-guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.

The Impact of Structural Racism on Continuity of Care at Pediatric Academic Primary Care Clinics.

OBJECTIVE: Using a structural racism framework, we assessed racial inequities in continuity of care, using the Usual Provider Continuity Index (UPC - the proportion of visits with the provider the patient saw most frequently out of all visits), in a set of large pediatric academic clinics. METHODS: We conducted a retrospective cohort study. Patients 12-24 months seen at three pediatric academic primary care clinics for any visit during October 1-31, 2021 were included. We then reviewed continuity for these patients in the preceding 12 months. Outcomes included each patient's UPC for all visits, and a modified UPC for well child checks only (UPC Well). Covariates included race, ethnicity, insurance, clinic site, age, sex, care management, or seeing a social worker. We evaluated for differences in outcomes using bivariate analyses and multivariable regression models. RESULTS: Our cohort included 356 patients (74% Black, 5% Hispanic, 85% Medicaid, 52% female, median age 15.8 months). The median UPC was 0.33 and median UPC Well was 0.40. Black patients had significantly lower median values for UPC (0.33 Black vs 0.40 non-Black, P < .01) and UPC Well (0.33 Black vs 0.50 non-Black, P < .01). There were similar inequities in continuity rates by insurance and clinic site. In multivariable models, clinic site was the only variable significantly associated with continuity. CONCLUSIONS: Clinic sites serving higher percentages of Black patients had lower rates of continuity. The main driver of racial inequities in continuity rates was at the institutional level.