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The cardiovascular outcomes, heart failure and kidney disease trials tell that the time to use Sodium Glucose Cotransporter 2 inhibitors is now.

ABSTRACT: Sodium glucose contrasporter 2 inhibitors (SGLT2i) were initially introduced as a novel class of modestly effective antiglycemics. Over the last 5?years, multiple members of this class have been examined for their cardiovascular safety, effects on heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD) in diverse populations with or without diabetes type 2. The plethora of studies and outcomes examined make it difficult for the practitioner to track the entirety of the evidence. SGLT2i improve cardiorenal outcomes and have a beneficial risk benefit ratio across populations with cardiovascular disease, HFrEF and kidney disease. In this quantitative review, we synthesize the data from the large outcomes trials about the benefits and risks of SGLT2i. SGLT2i reduce all cause, cardiovascular mortality, heart failure hospitalizations, need for dialysis and acute kidney injury as a class effect across a broad range of populations with diabetes Type 2 at risk for cardiovascular disease, patients with HFrEF or CKD with or without diabetes. While certain adverse events for example, diabetic ketoacidosis and genital mycotic infections are reproducibly increased by SGLT2i, the absolute increase in the risk of these complications is smaller than the absolute risk reductions conferred by SGLT2i. Other complications such as amputations, fractures and urinary tract infections are increased to a lesser degree, or not at all (e.g., hypoglycemia). Overall, SGLT2is appear to have a favorable safety profile and thus should be used by cardiologists, nephrologists, endocrinologists, primary care physicians when managing the cardiorenal risk of their patients.

SUBMITTER: Johansen ME

PROVIDER: S-EPMC7724239 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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The cardiovascular outcomes, heart failure and kidney disease trials tell that the time to use Sodium Glucose Cotransporter 2 inhibitors is now.

Johansen Michael E ME Argyropoulos Christos C

Clinical cardiology 20201109 12

Sodium glucose contrasporter 2 inhibitors (SGLT2i) were initially introduced as a novel class of modestly effective antiglycemics. Over the last 5 years, multiple members of this class have been examined for their cardiovascular safety, effects on heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD) in diverse populations with or without diabetes type 2. The plethora of studies and outcomes examined make it difficult for the practitioner to track the entirety of ...[more]

PMID: 33165977

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Project description:Despite current established therapy, heart failure (HF) remains a leading cause of hospitalization and mortality worldwide. Novel therapeutic targets are therefore needed to improve the prognosis of patients with HF. The EMPA-REG OUTCOME trial ([Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) demonstrated significant reductions in mortality and HF hospitalization risk in patients with type 2 diabetes mellitus (T2D) and cardiovascular disease with the antihyperglycemic agent, empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor. The CANVAS trial (Canagliflozin Cardiovascular Assessment Study) subsequently reported a reduction in 3-point major adverse cardiovascular events and HF hospitalization risk. Although SGLT2 inhibition may have potential application beyond T2D, including HF, the mechanisms responsible for the cardioprotective effects of SGLT2 inhibitors remain incompletely understood. SGLT2 inhibition promotes natriuresis and osmotic diuresis, leading to plasma volume contraction and reduced preload, and decreases in blood pressure, arterial stiffness, and afterload as well, thereby improving subendocardial blood flow in patients with HF. SGLT2 inhibition is also associated with preservation of renal function. Based on data from mechanistic studies and clinical trials, large clinical trials with SGLT2 inhibitors are now investigating the potential use of SGLT2 inhibition in patients who have HF with and without T2D. Accordingly, in this review, we summarize the key pharmacodynamic effects of SGLT2 inhibitors and the clinical evidence that support the rationale for the use of SGLT2 inhibitors in patients with HF who have T2D. Because these favorable effects presumably occur independent of blood glucose lowering, we also explore the potential use of SGLT2 inhibition in patients without T2D with HF or at risk of HF, such as in patients with coronary artery disease or hypertension. Finally, we provide a detailed overview and summary of ongoing cardiovascular outcome trials with SGLT2 inhibitors.

Project description:ImportanceEmerging evidence has consistently demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF) hospitalization and cardiovascular (CV) death among patients with HF. However, it remains unclear how long a patient needs to live to potentially benefit from SGLT2 inhibitors in this population.ObjectivesTo estimate the time to benefit from SGLT2 inhibitors among patients with HF.Design, setting, and participantsThis comparative effectiveness study systematically searched PubMed for completed randomized clinical trials about SGLT2 inhibitors and patients with HF published until September 5, 2022; 5 trials with the year of publication ranging from 2019 to 2022 were eventually included. Statistical analysis was performed from April to October 2022.InterventionAddition of SGLT2 inhibitors or placebo to guideline-recommended therapy.Main outcomes and measuresThe primary outcome was the time to first event of CV death or worsening HF, which was broadly comparable across the included trials.ResultsFive trials consisting of 21 947 patients with HF (7837 [35.7%] were female; mean or median age older than 65 years within each trial) were included. SGLT2 inhibitors significantly reduced the risk of worsening HF or CV death (hazard ratio [HR], 0.77 [95% CI, 0.73-0.82]). Time to first nominal statistical significance (P < .05) was 26 days (0.86 months), and statistical significance was sustained from day 118 (3.93 months) onwards. A mean of 0.19 (95% CI, 0.12-0.35) months were needed to prevent 1 worsening HF or CV death per 500 patients with SGLT2 inhibitors (absolute risk reduction [ARR], 0.002). Likewise, 0.66 (95% CI, 0.43-1.13) months was estimated to avoid 1 event per 200 patients with SGLT2 inhibitors (ARR, 0.005), 1.74 (95% CI, 1.07-2.61) months to avoid 1 event per 100 patients (ARR, 0.010), and 4.96 (95% CI, 3.18-7.26) months to avoid 1 event per 50 patients (ARR, 0.020). Further analyses indicated a shorter time to benefit for HF hospitalization and among patients with diabetes or HF with reduced ejection fraction.Conclusions and relevanceIn this comparative effectiveness research study of estimating the time to benefit from SGLT2 inhibitors among patients with HF, a rapid clinical benefit in reducing CV death or worsening HF was found, suggesting that their use may be beneficial for most individuals with HF.

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The cardiovascular outcomes, heart failure and kidney disease trials tell that the time to use Sodium Glucose Cotransporter 2 inhibitors is now.

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The cardiovascular outcomes, heart failure and kidney disease trials tell that the time to use Sodium Glucose Cotransporter 2 inhibitors is now.

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