Background To summarize the four recent sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials: Dapagliflozin Effect on CardiovascuLAR Events (DECLARE-TIMI 58), CANagliflozin CardioVascular Assessment Study (CANVAS) Program, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients–Removing Excess Glucose (EMPA–REG OUTCOME), Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), and explore the potential determinants for their cardiovascular, renal, and safety outcomes. Results The composite renal outcome event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 3.7, 7.0, 47%; 5.5, 9.0, 40%; 6.3, 11.5, 46%; 43.2, 61.2, 30% for DECLARE-TIMI 58, CANVAS, EMPA–REG OUTCOME, and CREDENCE, respectively (event definitions varied across trials). The major adverse cardiovascular (CV) event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 22.6, 24.2, 7%; 26.9, 31.5, 14%; 37.4, 43.9, 14%; 38.7, 48.7, 20% for DECLARE-TIMI 58, CANVAS, EMPA–REG OUTCOME, and CREDENCE, respectively. DECLARE-TIMI 58 had the fewest cardiorenal events and CREDENCE the most. These differences were presumably due to varying inclusion criteria resulting in DECLARE-TIMI 58 having the best baseline renal filtration function and CREDENCE the worst (mean estimated glomerular filtration rate 85.2, 76.5, 74, 56.2 mL/min/1.73 m 2 for DECLARE-TIMI 58, CANVAS, EMPA–REG OUTCOME, and CREDENCE, respectively). Additionally, CREDENCE had considerably higher rates of albuminuria (median urinary albumin-creatinine ratios (UACR) were 927, 12.3, and 13.1 mg/g for CREDENCE, CANVAS, and DECLARE-TIMI 58, respectively; EMPA–REG OUTCOME had 59.4% UACR < 30, 28.6% UACR > 30–300, 11.0% UACR > 300 mg/g). Conclusions Dapagliflozin, empagliflozin, and canagliflozin have internally and externally consistent and biologically plausible class effects on cardiorenal outcomes. Baseline renal filtration function and degree of albuminuria are the most significant indicators of risk for both CV and renal events. Thus, these two factors also anticipate the greatest clinical benefit for SGLT2i.

BackgroundVasoplegia is associated with adverse outcomes following cardiac surgery; however, its impact following left ventricular assist device implantation is largely unexplored.Methods and ResultsIn 252 consecutive patients receiving a left ventricular assist device, vasoplegia was defined as the occurrence of normal cardiac function and index but with the need for intravenous vasopressors within 48 hours following surgery for >24 hours to maintain a mean arterial pressure >70 mm Hg. We further categorized vasoplegia as none; mild, requiring 1 vasopressor (vasopressin, norepinephrine, or high‐dose epinephrine [>5 μg/min]); or moderate to severe, requiring ≥2 vasopressors. Predictors of vasoplegia severity were determined using a cumulative logit (ordinal logistic regression) model, and 1‐year mortality was evaluated using competing‐risks survival analysis. In total, 67 (26.6%) patients developed mild vasoplegia and 57 (22.6%) developed moderate to severe vasoplegia. The multivariable model for vasoplegia severity utilized preoperative Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile, central venous pressure, systolic blood pressure, and intraoperative cardiopulmonary bypass time, which yielded an area under the curve of 0.76. Although no significant differences were noted in stroke or pump thrombosis rates (P=0.87 and P=0.66, respectively), respiratory failure and major bleeding increased with vasoplegia severity (P<0.01). Those with moderate to severe vasoplegia had a significantly higher risk of mortality than those without vasoplegia (adjusted hazard ratio: 2.12; 95% confidence interval, 1.08–4.18; P=0.03).ConclusionsVasoplegia is predictive of unfavorable outcomes, including mortality. Risk factors for future research include preoperative INTERMACS profile, central venous pressure, systolic blood pressure, and intraoperative cardiopulmonary bypass time.

No abstract

tively (which did not require CVD). In conclusion, there is a need for large-scale studies of SGLT2i with matching inclusion/exclusion criteria and appropriate endpoints to ensure a truly direct comparison of the drugs.