Cardioprotective Potential of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Cancer Treated With Anthracyclines: An Observational Study.

Anthracyclines are pivotal in cancer treatment, yet their clinical utility is hindered by the risk of cardiotoxicity. Preclinical studies highlight the effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in mitigating anthracycline-induced cardiotoxicity. Nonetheless, the translation of these findings to clinical practice remains uncertain. This study aims to evaluate the safety and potential of SGLT2i for preventing cardiotoxicity in patients with cancer, without preexisting heart failure (HF), receiving anthracyclines therapy. Using the TriNetX Global Research Network, patients with cancer, without previous HF diagnosis, receiving anthracycline therapy were identified and classified into 2 groups based on SGLT2i usage. A 1:1 propensity score matching was used to control for baseline characteristics between the 2 groups. Patients were followed for 2 years. The primary end point was new-onset HF, and the secondary end points were HF exacerbation, new-onset arrhythmia, myocardial infarction, all-cause mortality, and all-cause hospitalization. Safety outcomes included acute renal failure and creatinine levels. A total of 79,074 patients were identified, and 1,412 were included post-matching (706 in each group). They comprised 53% females, 62% White, with a mean age of 62.5 ± 11.4 years. Over the 2-year follow-up period, patients on SGLT2i had lower rates of new-onset HF (hazard ratio 0.147, 95% confidence interval 0.073 to 0.294) and arrhythmia (hazard ratio 0.397, 95% confidence interval 0.227 to 0.692) compared with those not on SGLT2i. The incidence of all-cause mortality, myocardial infarction, all-cause hospitalization, and safety outcomes were similar between both groups. In conclusion, among patients with cancer receiving anthracycline therapy without preexisting HF, SGLT2i use demonstrates both safety and effectiveness in reducing anthracycline-induced cardiotoxicity, with a decreased incidence of new-onset HF, HF exacerbation, and arrhythmias.

Physical Activity, Air Pollution Exposure, and Lung Function Interactions Among Adults with COPD.

Rationale: Although physical activity is strongly encouraged for patients with chronic obstructive pulmonary disease (COPD), it is unknown if physical activity affects daily exposure to air pollution, or whether it attenuates or exacerbates the effects of pollution on the airways among adults with COPD. Methods: Thirty former smokers with moderate-to-severe COPD in Boston were followed for 4 non-consecutive months in different seasons. We assessed daily lung function (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]), prior-day personal pollutant exposure measured by portable air quality monitors (fine particulate matter [PM2.5] nitrogen oxide [NO2], and ozone [O3]), and daily step count. We constructed multi-level linear mixed-effects models with random intercepts for person and person-observation month, adjusting for demographic/seasonal covariates to test if step count was associated with daily pollution exposure, and if associations between prior-day pollution and lung function differed based on prior-day step count. Where effect modification was found, we performed stratified analyses by tertile of step count. Results: Higher daily step count was associated with higher same-day personal exposure to PM2.5, and O3 but not NO2. Each interquartile range (IQR) increment in step count was associated with 0.97 µg/m3 (95%CI: 0.30, 1.64) higher exposure to PM2.5 and 0.15 parts per billion (95% CI: -0.05, 0.35) higher exposure to O3 in adjusted models. We observed an interaction between prior-day NO2 and step count on FEV1 and FVC (Pinteraction<0.05) in which the negative associations between NO2 and lung function were reduced or absent at higher levels of daily activity. For example, FEV1 was 28.5mL (95%CI: -41.0, -15.9) lower per IQR of NO2 in the lowest tertile of step count, but there was no association in the highest tertile of step count (-1.6mL, 95% CI: -18.4, 15.2). Conclusions: Higher physical activity was associated with modestly higher daily exposure to PM2.5 and O3 and may attenuate the association between NO2 exposure and lung function.