Female underrepresentation in oncology clinical trials can result in outcome disparities. We evaluated female participant representation in US oncology trials by intervention type, cancer site, and funding. Data were extracted from the publicly available Aggregate Analysis of ClinicalTrials.gov database. Initially, 270,172 studies were identified. Following the exclusion of trials using Medical Subject Heading terms, manual review, those with incomplete status, non-US location, sex-specific organ cancers, or lacking participant sex data, 1650 trials consisting of 240,776 participants remained. The primary outcome was participation to prevalence ratio (PPR): percent females among trial participants divided by percent females in the disease population per US Surveillance, Epidemiology, and End Results Program data. PPRs of 0.8-1.2 reflect proportional female representation. Females represented 46.9% of participants (95% CI, 45.4-48.4); mean PPR for all trials was 0.912. Females were underrepresented in surgical (PPR 0.74) and other invasive (PPR 0.69) oncology trials. Among cancer sites, females were underrepresented in bladder (odds ratio [OR] 0.48, 95% CI 0.26-0.91, P = .02), head/neck (OR 0.44, 95% CI 0.29-0.68, P < .01), stomach (OR 0.40, 95% CI 0.23-0.70, P < .01), and esophageal (OR 0.40 95% CI 0.22-0.74, P < .01) trials. Hematologic (OR 1.78, 95% CI 1.09-1.82, P < .01) and pancreatic (OR 2.18, 95% CI 1.46-3.26, P < .01) trials had higher odds of proportional female representation. Industry-funded trials had greater odds of proportional female representation (OR 1.41, 95% CI 1.09-1.82, P = .01) than US government and academic-funded trials. Stakeholders should look to hematologic, pancreatic, and industry-funded cancer trials as exemplars of female participant representation and consider female representation when interpreting trial results.

BACKGROUND: Despite current treatment strategies for atherosclerotic vascular disease focusing on lifestyle modification and lowering cholesterol, a significant residual risk of major atherosclerotic complication remains, prompting investigation into lipoprotein(a) (Lp(a)) as a potential predictive biomarker. The objective of this study was to determine the usefulness of Lp(a) in identifying patients at high risk of incident extracoronary atherosclerotic vascular disease and complications. METHODS: Data from 460 544 participants in the UK Biobank with prospectively measured Lp(a) concentrations were included in this analysis. Cox proportional hazards regressions modeled the associations of Lp(a) concentrations with incident peripheral artery disease (PAD) and incident carotid artery stenosis and progression to the first major adverse limb event and the first stroke, respectively. RESULTS: Of the study participants, the median [interquartile range] age at study enrollment was 58 [51–64] years, 54.2% were male, 94.4% were European, 5.5% had diabetes, and 10.5% were smokers. Over a median follow-up time of 13.6 [12.9–14.4] years, 6347 (1.4%) and 1972 (0.43%) developed the first incidence of PAD and carotid stenosis, respectively. Among participants with prevalent PAD and carotid stenosis at enrollment, 196 (2.7%) and 67 (1.9%) progressed to the first incidence of major adverse limb event and stroke, respectively. Median Lp(a) concentrations were significantly different in those without atherosclerotic vascular disease at 19.5 nmol/L [7.6–73.5] compared with incident PAD at 25.3 nmol/L [8.3–107.3], progression to major adverse limb event at 33.3 nmol/L [8.7–158.2], incident carotid stenosis at 29.5 nmol/L [8.5–116.3], and carotid stenosis progression to stroke at 37.8 nmol/L [11.1–158.3]. The risk estimate per 75 nmol/L Lp(a) for incident PAD (hazard ratio [HR], 1.18 [95% CI, 1.15–1.20]; P <0.0001) was similar to that for incident carotid stenosis (HR, 1.17 [95% CI, 1.13–1.20]; P <0.0001). Among participants with PAD, those with high Lp(a) concentrations had 1.57 times the risk of developing major adverse limb event than participants with normal Lp(a) concentrations (95% CI, 1.14–2.16; P =0.006). Among participants with carotid stenosis, participants had 1.40 times the risk of developing an ischemic stroke with high Lp(a) concentrations, although this was not significant (95% CI, 0.81–2.40; P =0.228). CONCLUSIONS: High concentrations of Lp(a) are associated with both incident extracoronary atherosclerotic vascular disease and progression to major complications.

Clotting, anticoagulation, platelet consumption, and poor platelet function are major factors in clinical extracorporeal circulation (ECC). We have shown that nitric oxide-releasing (NOReL) coatings prevent thrombosis in a rabbit model of ECC without systemic anticoagulation. Nitric oxide-releasing prevents platelet adhesion and activation, resulting in preserved platelet count and function. Previous work has shown that activated platelets form platelet-derived microparticles (PMPs). These experiments were designed to determine if PMPs can identify platelet function during ECC. The objective of this study is to investigate the effects of NOReL on platelet activation and PMP formation during ECC. Uncoated ECCs, including with and without systemic heparin, and NOReL-coated ECCs, including DBHD/N₂O₂ and argatroban (AG)/DBHD/N₂O₂-coated ECCs without systemic heparin, were tested in a 4-hour rabbit thrombogenicity model. Before and after ECC exposure, platelets were stimulated with collagen, and PMPs were measured using flow cytometry. The uncoated ECCs clotted within the first hour, while the NOReL-coated ECCs circulated for 4 hours. During pre-ECC blood exposure, platelets stimulated with collagen produced PMPs. With post-ECC exposure, platelets from uncoated circuits generated less PMPs than baseline (mean ± SDs: 23246 ± 3611 baseline vs. 1300 ± 523 uncoated post circuit, p = 0.018) when stimulated with collagen. However, platelets from the AG/DBHD/N₂O₂-coated ECCs generated a greater number of PMPs as baseline values (23246 ± 3611 baseline vs. 37040 ± 3263 AG/DBHD/N₂O₂ post 4 hours circuit, p = 0.023). Blood exposure during ECC results in platelet activation and clotting in uncoated ECCs. The remaining circulating platelets have lost function, as demonstrated by the low PMP formation in response to collagen. AG/DBHD/N₂O₂-coated ECCs prevented significant platelet activation and clotting, while DBHD/N₂O₂ trended towards prevention of platelet activation. In addition, function of the circulating platelets was preserved, as demonstrated by PMP formation in response to collagen. These results indicate that PMPs may be an important measure of platelet activation during ECC. Platelet-derived microparticles may provide a simplified way to measure platelet function during clinical ECC.

The roles of lipoprotein(a) [Lp(a)] and related oxidized phospholipids (OxPLs) in the development and progression of coronary disease is known, but their influence on extracoronary vascular disease is not well-established. We sought to evaluate associations between Lp(a), OxPL apolipoprotein B (OxPL-apoB), and apolipoprotein(a) (OxPL-apo(a)) with angiographic extracoronary vascular disease and incident major adverse limb events (MALEs). Four hundred forty-six participants who underwent coronary and/or peripheral angiography were followed up for a median of 3.7 years. Lp(a) and OxPLs were measured before angiography. Elevated Lp(a) was defined as ≥150 nmol/L. Elevated OxPL-apoB and OxPL-apo(a) were defined as greater than or equal to the 75th percentile (OxPL-apoB ≥8.2 nmol/L and OxPL-apo(a) ≥35.8 nmol/L, respectively). Elevated Lp(a) had a stronger association with the presence of extracoronary vascular disease compared to OxPLs and was minimally improved with the addition of OxPLs in multivariable models. Compared to participants with normal Lp(a) and OxPL concentrations, participants with elevated Lp(a) levels were twice as likely to experience a MALE (odds ratio: 2.14, 95% confidence interval: 1.03, 4.44), and the strength of the association as well as the C statistic of 0.82 was largely unchanged with the addition of OxPL-apoB and OxPL-apo(a). Elevated Lp(a) and OxPLs are risk factors for progression and complications of extracoronary vascular disease. However, the addition of OxPLs to Lp(a) does not provide additional information about risk of extracoronary vascular disease. Therefore, Lp(a) alone captures the risk profile of Lp(a), OxPL-apoB, and OxPL-apo(a) in the development and progression of atherosclerotic plaque in peripheral arteries.