Empagliflozin and Risk of Incident Gout: Analysis from the EMPagliflozin Comparative Effectiveness and SafEty (EMPRISE) Cohort Study.

BACKGROUND: Hyperuricemia is frequently observed in patients with type 2 diabetes (T2D) and is associated with increased risk of gout and cardiovascular disease (CVD). Empagliflozin lowers serum urate levels by enhancing its urinary excretion. OBJECTIVE: To compare initiators of empagliflozin vs dipeptidyl peptidase-4 inhibitor (DPP4i) and initiators of empagliflozin vs glucagon-like peptide-1 receptor agonist (GLP-1RA) with respect to the risk of incident gout events. DESIGN AND PARTICIPANTS: Using three claims-based datasets from 08/2014 to 09/2019, we generated two cohorts (cohort 1: empagliflozin vs DPP4i; cohort 2: empagliflozin vs GLP-1RA) of adult patients with T2D and without prior history of gout or gout-specific medication dispensing separately in each dataset. To assess the risk of incident gout, we estimated hazard ratios (HR) and rate differences (RD) per 1000 person-years (PY) with their 95% confidence intervals (CI) before and after 1:1 propensity score (PS) matching adjusting for 141 baseline covariates. KEY RESULTS: We identified 102,262 pairs of 1:1 propensity score-matched adults in cohort 1 and 131,216 pairs in cohort 2. Over a mean follow-up period of 8 months on treatment, the risk of gout was lower in patients initiating empagliflozin compared to DPP4i (HR = 0.69: 95% CI (0.60-0.79); RD = - 2.27: 95% CI (- 3.08, 1.46)) or GLP-1RA (HR = 0.83: 95% CI (0.73-0.94); RD = - 0.99: 95% CI (- 1.66, - 0.32)). Results were consistent across subgroups (sex, age, body mass index, chronic kidney disease, heart failure, cardiovascular disease, and concurrent diuretic use) and sensitivity analyses. CONCLUSIONS: Among adults with T2D, the initiation of empagliflozin vs a DPP4i or GLP-1RA was associated with lower risk of incident gout, complementing results from a post hoc analysis of the EMPA-REG OUTCOME trial and previously published observational research focusing on the sodium-glucose co-transporter-2 inhibitor class in more narrowly defined study populations.

Timing of blood pressure medications and intradialytic hypotension.

Intradialytic hypotension (IDH) is a prevalent yet serious complication of hemodialysis, associated with decreased quality of life, inadequate dialysis, vascular access thrombosis, global hypoperfusion, and increased cardiovascular and all-cause mortality. Current guidelines recommend antihypertensive medications be given at night and held the morning of dialysis for affected patients. Despite little evidence to support this recommendation, more than half of patients on dialysis may employ some form of this method. In this article, we will review the available evidence and clinical considerations regarding timing of blood pressure medications and occurrence of IDH, and conclude that witholding BP medications before hemodialysis should not be a routine practice.

Application of the Quadruple Aim to evaluate the operational impact of a telemedicine program.

BACKGROUND: In response to the COVID-19 pandemic, telemedicine utilization has increased dramatically, yet most institutions lack a standardized approach to determine how much to invest in these programs. METHODS: We used the Quadruple Aim to evaluate the operational impact of CardioClick, a program replacing in-person follow-up visits with video visits in a preventive cardiology clinic. We examined data for 134 patients enrolled in CardioClick with 181 video follow-up visits and 276 patients enrolled in the clinic's traditional prevention program with 694 in-person follow-up visits. RESULTS: Patients in CardioClick and the cohort receiving in-person care were similar in terms of age (43 vs 45 years), gender balance (74% vs 79% male), and baseline clinical characteristics. Video follow-up visits were shorter than in-person visits in terms of clinician time (median 22 vs 30 min) and total clinic time (median 22 vs 68 min). Video visits were more likely to end on time than in-person visits (71 vs 11%, p < .001). Physicians more often completed video visit documentation on the day of the visit (56 vs 42%, p = .002). CONCLUSIONS: Implementation of video follow-up visits in a preventive cardiology clinic was associated with operational improvements in the areas of efficiency, patient experience, and clinician experience. These benefits in three domains of the Quadruple Aim justify expanded use of telemedicine at our institution. IMPLICATIONS: The Quadruple Aim provides a framework to evaluate telemedicine programs recently implemented in many health systems. LEVEL OF EVIDENCE: Level III (retrospective comparative study).

Canagliflozin, serum magnesium and cardiovascular outcomes-Analysis from the CANVAS Program.

BACKGROUND: Patients with type 2 diabetes (T2D) are predisposed to derangements in serum Magnesium (Mg), which may have implications for cardiometabolic events and outcomes. In clinical trials, participants with T2D randomized to sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown mild to moderate increases in serum Mg from baseline levels. This post hoc analysis assesses the relation between serum Mg with cardiovascular outcomes in 10,140 participants of the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program. METHODS: We evaluated the association of baseline serum Mg with the primary composite end point of death from cardiovascular causes, non-fatal myocardial infarction, and non-fatal stroke, and tested whether this association is modified by baseline serum Mg. Using mediation analysis, we determined whether change in serum Mg post-randomization mediates the beneficial effect of canagliflozin on cardiovascular outcomes. RESULTS: Mean serum Mg levels at baseline were 0.77 ± 0.09 mmol/L in both canagliflozin group and placebo groups. The canagliflozin group experienced an average increase in serum Mg by 0.07 mmol/L (95% CI, 0.065-0.072 mmol/L; p < .001) for the duration of the trial. We found no association between baseline serum Mg levels and the primary composite end point, and no evidence of effect modification by baseline Mg levels. Change in serum Mg post-randomization was not a mediator of the effects of canagliflozin on cardiovascular outcomes. CONCLUSIONS: In participants of the CANVAS Program, baseline and post-randomization serum Mg levels are not associated with cardiovascular outcomes.

SGLT2 Inhibitor-Induced Euglycemic Diabetic Ketoacidosis: A Case Report.

Euglycemic diabetic ketoacidosis is a rare but serious adverse effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors. We present a case of a woman in her 40s with type 2 diabetes mellitus hospitalized for revascularization for moyamoya disease who developed empagliflozin-associated euglycemic diabetic ketoacidosis despite having stopped the medication before admission. Surgical stress, acute postoperative illness, and decreased carbohydrate intake are postulated to be contributing factors to the development of ketosis in this patient, while near-normal glucose levels initially suggested nondiabetic ketoacidosis physiology and led to delayed diagnosis and treatment. Patients with type 2 diabetes mellitus may develop diabetic ketoacidosis during states of relative insulinopenia, most frequently from inadequate medication or intercurrent illness. During periods of carbohydrate deficiency, volume depletion, and upregulation of counter-regulatory stress hormones, SGLT2 inhibitor therapy can promote lipolysis and ketogenesis while maintaining euglycemia. Clinical considerations to ensure safe SGLT2 inhibitor therapy include appropriate holding parameters, timely diagnosis of euglycemic diabetic ketoacidosis, and recognition that the pharmacologic effects of SGLT2 inhibitor treatment may persist beyond several half-lives of elimination.

Factors Associated With Failure to Achieve the Intensive Blood Pressure Target in the Systolic Blood Pressure Intervention Trial (SPRINT).

SPRINT (Systolic Blood Pressure Intervention Trial) found that randomization of nondiabetic participants at high cardiovascular risk to an intensive (systolic blood pressure [SBP] <120 mm Hg) versus standard (SBP <140 mm Hg) target resulted in 25% risk reduction in the first cardiovascular composite event (ie, cardiovascular death or nonfatal myocardial infarction, stroke, or hospitalization for heart failure) and a 27% risk reduction in all-cause mortality. In this post hoc analysis, we sought to determine the factors associated with failure to achieve the SBP target in 4678 SPRINT participants randomized to the intensive treatment group. Using a generalized estimating equation model, we assessed variables associated with failure to achieve the intensive SBP target as a repeated outcome collected during serial follow-up visits, including the occurrence of serious adverse events. In the multivariable model adjusted for baseline demographic, clinical, and laboratory variables, older age, higher SBP, underlying chronic kidney disease, higher number of antihypertensives, and moderate cognitive impairment at screening were associated with failure to achieve the intensive SBP target. Occurrence of a serious adverse event during the trial was associated with 20% higher odds of failure to achieve the SBP target. Participants of Hispanic ethnicity had 47% lower odds of failure to achieve the intensive SBP target relative to non-Hispanic Whites. Understanding barriers to achieving intensive SBP targets should allow clinicians to optimize management of hypertension in patients at high risk for cardiovascular disease.