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Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin) are a new class of heart failure medications that have previously been exclusively utilized in the management of type 2 diabetes mellitus (T2DM). The rationale for using SGLT-2 inhibitors in patients with heart failure has stemmed from recent landmark clinical trials in T2DM in which reductions in mortality and hospitalization for heart failure were first observed. On the basis of these robust outcomes, empagliflozin has further been evaluated in heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction and dapagliflozin solely in the management of HFrEF. While cardiovascular outcomes among each agent vary depending on the patient population, updates among both the American and European guidelines have included SGLT-2 inhibitors as pillars of therapy. The exact mechanisms for how SGLT-2 inhibitors are beneficial in heart failure are unknown, but current hypotheses include multiple metabolic and hemodynamic mechanisms. The purpose of this review is to summarize available literature focusing on the use of the SGLT-2 inhibitors as adjunctive therapy in heart failure, as well as evaluate mechanisms for heart failure benefit, adverse effects, and practical considerations for using these agents in the clinical setting.

Background Carbapenems’ broad spectrum of activity may make these agents appealing for empiric use; however, their use is associated with development of Clostridioides difficile infection (CDI) and multi-drug resistance. Selective use of carbapenems is vital in maintaining their effectiveness. Our study aimed to examine the impact of meropenem restriction criteria on utilization and patient outcomes. Methods This single-center, quasi-experimental study was conducted at an academic medical center where an initial medication use analysis found frequent inappropriate meropenem utilization. The antimicrobial stewardship team developed restriction criteria and implemented a pilot in February 2022. Investigators aimed to determine how restriction criteria affected meropenem utilization across 8 weeks in the pre-implementation period compared to the post-implementation period. The primary outcome was to compare the inappropriateness of meropenem utilization. Secondary outcomes included comparison of days of therapy per 1000 patient-days (DOT/1000 PD), hospital length of stay (LOS), frequency of CDI, and acquisition cost. Results Across the 8 week timeframes, reductions in inappropriate meropenem use (64.5% vs 12.8%; p< 0.001), duration of therapy (5.8 [3.2-7.3] vs. 2.4 [1.0-5.5] days, p< 0.0001), and utilization (30.5 vs. 8.3 DOT/1000 PD, p=0.04) in the pre- and post-implementation periods, respectively, were observed. Total number of meropenem orders decreased by 65% (p< 0.001). Implementation of restriction criteria also resulted in decreased median hospital LOS between periods (11.9 [7.8-20.4] vs. 9.2 [5.4-15.2] days, p=0.05). There was no difference in frequency of CDI (2 vs. 0, p=0.99). Projected annual cost savings was approximately $57,300. Conclusion Implementation of antimicrobial stewardship-initiated restriction criteria can reduce inappropriate utilization of meropenem, overall number of orders, and total duration of therapy. Disclosures Kerry O. Cleveland, MD, AbbVie: Honoraria|Cumberland: Honoraria|Merck: Honoraria|Pfizer: Honoraria.

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Severe bleeding remains the most significant adverse effect associated with both warfarin and the direct oral anticoagulant agents. Due to the life-threatening nature of these bleeds, knowledge and understanding of agents that are able to rapidly overcome the anticoagulation effects of these medications is paramount to their use. Worldwide, the most commonly used agent for this indication is prothrombin complex concentrate (PCC). This review summarizes the evidence on the use of PCC in this population and provides practical information regarding patient-specific administration considerations.