Citations

Abstract Background While the cardioprotective effects of glucagon-like peptide -1 (GLP-10) agonists are well-documented in diabetic patients, their impact on cardiovascular outcomes in patients with obesity without diabetes mellitus remains debated. Purpose This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effects of GLP-1 on cardiovascular outcomes in patients with obesity without diabetes mellitus. Methods A systematic review and meta-analysis synthesizing RCTs were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through December 26th, 2023. Dichotomous data were pooled using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). Results We included 19 RCTs with a total of 32,884 patients. There was no difference between GLP-1 agonists and placebo regarding cardiovascular mortality (RR: 0.85, 95% CI [0.71- 1.01], P= 0.07). However, GLP-1 agonists significantly decreased the incidence of all-cause mortality (RR 0.83, 95% CI 0.72 to 0.94, p < 0.0001), non-cardiovascular mortality (RR 0.78, 95% CI 0.63 to 0.96, p = 0.02), and myocardial infarction (RR 0.73, 95% CI 0.62 to 0.87, p < 0.0001). Also, GLP-1 agonists significantly increased the incidence of any adverse events (RR 1.11, 95% CI 1.05 to 1.16, p < 0.0001), with no difference regarding the incidence of serious adverse events. Conclusion GLP-1 agonists not only demonstrated substantial benefits in reducing cardiovascular risks, including all-cause mortality and myocardial infarction, but also effectively promoted weight loss and improved lipid profiles and blood pressure control. However, their use is accompanied by a higher incidence of gastrointestinal adverse effects and heterogeneity in outcomes, highlighting the need for individualized treatment approaches.

Abstract Background Left Ventricular Assist Devices (LVADs) and heart transplantation stand out as the two well-established and effective therapeutic approaches for managing patients with advanced heart failure. Exercise-based cardiac rehabilitation (EBCR) has been demonstrated to improve functional capacity in patients with LVAD. Purpose We aim to assess the efficacy and safety of EBCR in patients with LVAD. Also, to compare high-intensity (HIT) versus moderate-intensity (MIT) EBCR regimens in patients with LVAD. Methods A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) studies obtained from PubMed, Embase Cochrane, Scopus, and WOS until January 2024. We used the fixed-effects model to report dichotomous outcomes using risk ratio (RR) and continuous outcomes using standardized mean difference (SMD) with a 95% confidence interval (CI). Results Six RCTs with 160 patients were included. There was no significant difference between EBCR and standard care regarding peak VO2 change [SMD: 0.24 with 95% CI (-0.14, 0.62), P= 0.21] and six-minute walk distance (6-MWD) change [SMD: 0.28 with 95% CI (-0.11, 0.66), P= 0.16]. Also, there was no significant difference between HIT and MIT exercise regarding peak VO2 change [SMD: 0.20 with 95% CI (-0.41, 0.82), P= 0.52] and 6-MWD change [SMD: 0.07 with 95% CI (-0.54, 0.69), P= 0.81]. Moreover, EBCR was associated with a significant decrease in the incidence of any adverse events when compared to usual care with [RR: 0.80 with 95% CI (0.65, 0.99), P= 0.04], while there was no significant difference between HIT and MIT exercise regarding the incidence of any adverse events [RR: 0.38 with 95% CI (0.02, 9.22), P= 0.55]. Conclusion EBCR did not improve functional capacity in patients with LVAD, with no significant effect on peak VO2 or 6-MWD.

Abstract Despite the widespread use of carfilzomib (K) in relapsed/refractory multiple myeloma (RRMM), there is no consensus on optimal K dose in milligrams per square meter (mg/m2) or dosing schedule. We assessed three modern K prescribing patterns in RRMM using a large United States electronic health record-derived database. Our final cohort (n = 486) included 136 patients (28.0%) who received K 56 mg/m2 once weekly (K56-1x), 86 (17.7%) who received 56 mg/m2 twice weekly (K56-2x), and 264 (54.3%) who received 70 mg/m2 once weekly (K70-1x). Between 2016 and 2023, once-weekly dosing became more common: K70-1x proportions changed from 21.1% in 2016 to 50.6% in 2023, K56-1x from 15.8% to 37.0%, and K56-2x from 63.2% to 12.3%. Median real-world progression-free survival was 13.0 months [95% confidence interval (CI) 11.2-20.7] for K56-1x, 13.2 months (95% CI 9.0-28.1 months) for K56-2x, and 10.9 months (95% CI 9.9-15.3 months) for K70-1x; these differences were not statistically significant (log-rank p = 0.46). The prevalence of heart failure was comparable (<5% in all cohorts). In summary, our findings do not support improved outcomes with twice-weekly carfilzomib in RRMM. K56-1x may provide the best balance of efficacy, safety, and avoidance of time toxicity from frequent infusions.

Posttransplant diabetes mellitus (PTDM) is associated with significant morbidity and mortality in liver transplant recipients (LTRs). We used the Organ Procurement and Transplantation Network (OPTN) database to compare the incidence of developing PTDM across the United States and develop a risk prediction model for new-onset PTDM using OPTN region as well as donor-related, recipient-related, and transplant-related factors. All US adult, primary, deceased donor, LTRs between January 1, 2007, and December 31, 2016, with no prior history of diabetes noted, were identified. Kaplan-Meier estimators were used to calculate the cumulative incidence of PTDM, stratified by OPTN region. Multivariable Cox proportional hazards models were fitted to estimate hazards of PTDM in each OPTN region and build a risk prediction model, through backward selection. Cumulative incidence of PTDM at 1 year, 3 years, and 5 years after transplant was 12.0%, 16.1%, and 18.9%, respectively. Region 3, followed by regions 8, 2, and 9, had the highest adjusted hazards of developing PTDM. Inclusion of OPTN region in a risk prediction model for PTDM in LTRs (including recipient age, sex, race, education, insurance coverage, body mass index, primary liver disease, cold ischemia time, and donor history of diabetes) modestly improved performance (C-statistic = 0.60). In patients without pre-existing, confirmed diabetes mellitus, the incidence of PTDM in LTRs varied across OPTN regions, with the highest hazards in region 3, followed by regions 8, 2, and 9. The performance of a novel risk prediction model for PTDM in LTRs has improved performance with the inclusion of the OPTN region. Vigilance is recommended to centers in high-risk regions to identify PTDM and mitigate its development.