ABSTRACT
Atrial fibrillation (AF) is common, but there are limited data to guide selection of rate control medications (RCM). Reasons for selection are multivariable, and the impact on outcomes is unknown. We investigated prescribing patterns of RCM among patients with AF. Using a nationwide database, we identified 135,927 patients with AF. We stratified by baseline presence of heart failure with reduced ejection fraction (HFrEF) and examined prescription rates of RCM as a function of clinical variables. We also evaluated associations with clinical outcomes. Beta blockers (BB) were most commonly prescribed (44.6%), then calcium channel blockers (CCB) (14.0%) and digoxin (8.6%). Patients prescribed BB were more likely male (45.6% vs 43.4%, p < 0.0001), patients prescribed CCB were less likely male (12.0% vs 16.3%, p < 0.0001). There were higher rates of HF hospitalization (HFH) among females and those with Medicaid. Randomized trials are needed to define optimal choice of RCM.
ABSTRACT
Multiple myeloma is a blood cell cancer and can cause symptoms such as bone loss and fatigue. Recent studies have shown that the bone marrow microenvironment may mediate tumor proliferation, drug resistance, and migration of the multiple myeloma cells. Synthetic triterpenoids have been used for the treatment of cancer due to their antiproliferative and anti-inflammatory effects. The objective of this study is to examine the effect of 2-cyano-3, 12 dioxoolean-1,9-dien-28-oic acid (CDDO) derivatives on human multiple myeloma cells. Three CDDO derivatives, such as CDDO-methyl ester, CDDO-trifluroethyl amide, and CDDO-imidazolide (Im), were tested on the growth of human multiple myeloma cells. Our results show that all CDDO derivatives decrease the viability of multiple myeloma cells in a dose- and time-dependent manner, with CDDO-Im being the most potent. CDDO-Im was selected to investigate whether its inhibitory effect on multiple myeloma cell growth is due to cell cycle arrest and induction of apoptosis. The results suggest that CDDO-Im may inhibit cell cycle progression in the G0/G1 phase and induce the intrinsic apoptotic pathway. The effect of CDDO-Im on multiple myeloma cells was evaluated in a Transwell model using myeloma cells co-culturing with human HS-5 stromal cells to simulate the bone marrow microenvironment in vitro. The results showed that CDDO-Im induced multiple myeloma cell apoptosis in the presence of HS-5 cells, albeit to a lower extent than in multiple myeloma cells cultured alone. In conclusion, our data suggest that CDDO-Im inhibits the growth of multiple myeloma cells, either cultured alone or co-cultured with bone marrow stromal cells, through the induction of apoptosis.
