Badve SV, Perkovic V, Jha V
… +35 more, Ramachandran R, Mushahar L, Menne J, De Vriese AS, Rossignol P, Flahault A, Al Ammari M, Skhiri H, Walsh M, Collister D, Liew A, Billot L, Bompoint S, Devaux A, Jun M, Lin E, Ramos da Cruz A, Ha JT, Eikelboom JW, Shaman A, Jardine MJ, Jesudason S, Wong MG, Anderson CS, Garg AX, Heerspink HJL, Monaghan H, Patel A, Mark PB, Wheeler DC, Lv J, Zuo L, Pilmore H, Gallagher M, TRACK Trial Investigators
IMPORTANCE: Approximately 10% to 15% of patients with advanced chronic kidney disease (CKD) experience a fatal or nonfatal cardiovascular event annually. The effects of antithrombotic therapies on cardiovascular events i...IMPORTANCE: Approximately 10% to 15% of patients with advanced chronic kidney disease (CKD) experience a fatal or nonfatal cardiovascular event annually. The effects of antithrombotic therapies on cardiovascular events in patients with advanced CKD are unknown. OBJECTIVE: To determine whether low-dose rivaroxaban reduces rates of adverse cardiovascular events compared with placebo in patients with advanced CKD. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial conducted at 90 centers in 12 countries. Eligible participants were adults with CKD stage 4 or 5 and patients with dialysis-dependent kidney failure. Participants had a history of either coronary artery disease; nonhemorrhagic, nonlacunar stroke; peripheral artery disease; diabetes; or were 65 years or older. Enrollment occurred between January 2021 and July 2025. The trial was stopped early on August 7, 2025, for lack of efficacy. Final follow-up occurred on October 30, 2025. Statistical analyses were conducted in February and March 2026. INTERVENTIONS: Patients were randomized 1:1 to receive rivaroxaban 2.5 mg twice daily or placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or a peripheral artery disease event. The primary safety outcome was major bleeding. RESULTS: Of 1458 randomized patients (mean [SD] age, 63.2 [11.6] years, 432 [29.6%] female), 1360 (93.3%) completed follow-up. During a median follow-up of 1.7 years, the primary outcome occurred in 164 patients (22.6%) in the low-dose rivaroxaban group and 151 (20.7%) in the placebo group (13.0 vs 11.8 events per 100 person-years; hazard ratio, 1.09 [95% CI, 0.87-1.36]; P = .46). Major bleeding occurred in 64 patients (8.8%) receiving low-dose rivaroxaban and 44 (6.0%) receiving placebo (5.1 vs 3.4 events per 100 person-years; hazard ratio, 1.51 [95% CI, 1.02-2.22]; P = .04). CONCLUSIONS AND RELEVANCE: In patients with advanced CKD at high cardiovascular risk, low-dose rivaroxaban did not reduce the risk of a composite cardiovascular outcome. Major bleeding rates were significantly higher in the low-dose rivaroxaban group compared with the placebo group. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03969953.
IMPORTANCE: Lower estimated glomerular filtration rate (eGFR) is associated with increased rates of death and kidney and cardiovascular events. Associations of measured GFR (mGFR) with outcomes remain unclear. OBJECTIVE:...IMPORTANCE: Lower estimated glomerular filtration rate (eGFR) is associated with increased rates of death and kidney and cardiovascular events. Associations of measured GFR (mGFR) with outcomes remain unclear. OBJECTIVE: To quantify associations between mGFR and adverse clinical outcomes and to compare these with eGFR-based associations. DESIGN, SETTING, AND PARTICIPANTS: Retrospective observational cohort study of 6174 adults from Stockholm, Sweden, between January 1, 2011, and December 31, 2021. EXPOSURE: Measured GFR was obtained based on plasma clearance of intravenously administered iohexol (primary independent variable of interest). Estimated GFR was calculated with plasma creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys), using the Chronic Kidney Disease Epidemiology Collaboration 2021 and 2012 equations. MAIN OUTCOMES AND MEASURES: Primary outcomes were all-cause mortality and kidney failure with replacement therapy. Associations of each GFR measure with outcomes were evaluated using hazard ratios adjusted for age, sex, body mass index (calculated as weight in kilograms divided by height in meters squared), medical history, medications, and urine albumin to creatinine ratio. RESULTS: Of 6174 participants (median age, 59 years [IQR, 43-69]; 3686 [60%] were male and 2488 [40%] were female), 1977 (32%) died and 426 (6.9%) developed kidney failure with replacement therapy during a median follow-up of 5.9 years (IQR, 3.0-8.8 years). Compared with a baseline mGFR of 90 mL/min/1.73 m2, an mGFR of 60 mL/min/1.73 m2 was associated with higher rates of all-cause mortality (27.6 vs 22.4 per 1000 person-years; hazard ratio [HR], 1.21; 95% CI, 1.14-1.28) and kidney failure with replacement therapy (1.2 vs 0.4 per 1000 person-years; HR, 2.85; 95% CI, 2.06-3.94). For all-cause mortality, associations for eGFRcr-cys did not significantly differ from those for mGFR (ratio of HRs [RHRs] at 60 mL/min/1.73 m2, 1.03; 95% CI, 0.96-1.10), whereas eGFRcr underestimated the mGFR-based association (RHR, 0.87; 95% CI, 0.79-0.95) and eGFRcys overestimated it (RHR, 1.17; 95% CI, 1.08-1.27). CONCLUSIONS AND RELEVANCE: Among adults in Sweden, mGFR values of 60 mL/min/1.73 m2 were associated with higher rates of all-cause mortality and kidney failure compared with mGFR values of 90 mL/min/1.73 m2, supporting the current GFR threshold of 60 mL/min/1.73 m2 to define chronic kidney disease. Associations of mGFR with mortality were most closely represented by the association of eGFRcr-cys with mortality, whereas eGFRcr underestimated and eGFRcys overestimated mortality risk.
IMPORTANCE: Preoperative and perioperative nivolumab improve event-free survival in resectable non-small cell lung cancer. The role of adjuvant nivolumab after upfront surgery is unknown. OBJECTIVE: To determine whether...IMPORTANCE: Preoperative and perioperative nivolumab improve event-free survival in resectable non-small cell lung cancer. The role of adjuvant nivolumab after upfront surgery is unknown. OBJECTIVE: To determine whether adjuvant nivolumab improves disease-free survival and overall survival in patients with resected non-small cell lung cancer with any tumor programmed death-ligand 1 (PD-L1) expression and in those with at least 50% PD-L1 expression. DESIGN, SETTING, AND PARTICIPANTS: This open-label, randomized phase 3 study enrolled participants from May 2016 through September 2019, with median follow-up of 72.6 months at the data cutoff in December 2025. The study was conducted at 378 centers in the US National Clinical Trials Network. Patients were identified through a screening trial. Those with resected tumors at least 4 cm and/or who were lymph node positive (N1/N2) were eligible for inclusion after completion of planned standard adjuvant therapy if the tumor was adenocarcinoma without sensitizing sequence variants in EGFR and ALK or squamous cell carcinoma. INTERVENTION: Patients were randomized in a 1:1 ratio to receive nivolumab 480 mg intravenously every 4 weeks for up to 1 year or standard care observation. MAIN OUTCOMES AND MEASURES: Co-primary end points were disease-free survival in the intention-to-treat population and in those with tumoral PD-L1 expression at least 50%. Overall survival was examined if the corresponding test of disease-free survival was statistically significant. RESULTS: A total of 466 patients (median age, 66 years; 241 [52%] male) were assigned to receive nivolumab and 469 (median age, 67 years; 245 [52%] male) to undergo standard care observation. The median duration of follow-up was 72.6 months. The trial was stopped for futility at 75% information. In the intention-to-treat population, median disease-free survival was 71.3 months with nivolumab and 68.8 months with observation (hazard ratio for progression or death, 0.97 [97% CI, 0.79-1.20]; [95% CI, 0.81-1.17]; 1-sided P = .39). In the subset of participants with PD-L1 of at least 50%, median disease-free survival was 89.8 months with nivolumab and 78.5 months with observation (hazard ratio for progression or death, 0.86 [98% CI, 0.55-1.34]; [95% CI, 0.59-1.25]; 1-sided P = .22). CONCLUSIONS AND RELEVANCE: Adjuvant nivolumab was not associated with improved disease-free survival in patients with resected non-small cell lung cancer without sensitizing EGFR and ALK alterations when given after planned adjuvant chemotherapy and/or radiotherapy. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02595944.
IMPORTANCE: Helicobacter pylori infection is the leading cause of gastric cancer, yet the economic value of population-based screening and eradication remains uncertain. OBJECTIVE: To project the lifetime health benefits...IMPORTANCE: Helicobacter pylori infection is the leading cause of gastric cancer, yet the economic value of population-based screening and eradication remains uncertain. OBJECTIVE: To project the lifetime health benefits and costs of invitation to 1-time H pylori stool antigen testing added to biennial fecal immunochemical test (FIT) screening compared with FIT alone. DESIGN, SETTING, AND PARTICIPANTS: Lifetime cost-effectiveness analysis conducted using a Markov decision-analytic model to simulate a cohort informed by a pragmatic randomized clinical trial in Changhua County, Taiwan. The model adopted a 30-year time horizon and projected long-term outcomes, including gastric and colorectal cancer mortality, quality-adjusted life-years (QALYs; incorporating both life expectancy and health-related quality of life), and health care expenditures. Costs were evaluated from a societal perspective. One-way and probabilistic sensitivity analyses were performed. Future costs and QALYs were discounted at an annual rate of 3%. EXPOSURES: Helicobacter pylori stool antigen testing plus FIT or FIT alone. MAIN OUTCOMES AND MEASURES: Incremental cost-effectiveness ratio of invitation for H pylori stool antigen testing plus FIT vs FIT alone, measured as the additional cost required to gain 1 QALY per person. Secondary outcomes included net monetary benefit and benefit-cost ratio. RESULTS: Compared with FIT alone, invitation to co-testing was more effective and less expensive (dominant), with a base-case cost-saving incremental cost-effectiveness ratio of $2094 per QALY gained (95% CI, $12 359 saved to $7291 additional cost). This resulted in a positive net monetary benefit, indicating that health benefits exceeded costs, and a benefit-cost ratio of 5.08, indicating an approximately 5-fold return on investment in the Taiwanese population. At a willingness-to-pay threshold of 1 × the Taiwan gross domestic product per QALY ($33 365), invitation to co-testing remained cost-saving in 65.7% of simulations. From a US cost perspective, invitation to co-testing was not cost-saving but remained cost-effective at the trial base-case H pylori prevalence. Sensitivity analyses identified H pylori prevalence as the dominant driver; co-testing exceeded a $100 000-per-QALY threshold when prevalence fell below 21.9%. CONCLUSIONS AND RELEVANCE: In a pragmatic real-world setting with incomplete adherence, invitation to combined H pylori stool antigen testing and FIT was more cost-effective than FIT alone, improving lifetime outcomes and yielding cost savings in Taiwan while remaining cost-effective in higher-cost settings under moderate H pylori prevalence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01741363.