Dataset Information

Comparing angiotensin receptor-neprilysin inhibitors with sodium-glucose cotransporter 2 inhibitors for heart failure with diabetes mellitus.

ABSTRACT:

Background and aims

Clinical comparisons of angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) treatment in patients with HFrEF and T2DM are limited. This study evaluated the clinical outcomes and treatment benefits of SGLT2i versus ARNI treatment in patients with HFrEF and T2DM in a large real-world data set.

Methods

We identified 1487 patients with HFrEF and T2DM who were undergoing ARNI or SGLT2i treatment for the first time (n = 647 and 840, respectively) between January 1, 2016, and December 31, 2021, and with clinical outcomes of CV death, hospitalization for heart failure (HHF), composite CV outcomes, or renal outcomes.

Results

The HHF risk reduction conferred by SGLT2i treatment was more significant than that conferred by ARNI treatment (37.7% vs. 30.4%; 95% confidence interval [CI] 1.06-1.41). SGLT2i use conferred significantly greater renal protection against the doubling of serum creatinine (13.1% vs. 9.3%; 95% CI 1.05-1.75), an estimated glomerular filtration rate decline of > 50% (24.9% vs. 20.0%; 95% CI 1.02-1.45), and progression to end-stage renal disease (3.1% vs. 1.5%; 95% CI 1.62-5.23). The improvements in echocardiographic parameters were comparable between the groups.

Conclusions

Compared with ARNI treatment, SGLT2i treatment was associated with a more significant HHF risk reduction and greater preservation of renal function in patients with HFrEF and T2DM. This study also supports the prioritization of SGLT2i use in these patients when patients' conditions or economic resources need to be considered.

SUBMITTER: Tsai ML

PROVIDER: S-EPMC10214563 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

Comparing angiotensin receptor-neprilysin inhibitors with sodium-glucose cotransporter 2 inhibitors for heart failure with diabetes mellitus.

Tsai Ming-Lung ML Lin Yuan Y Lin Ming-Shyan MS Tsai Tzu-Hsien TH Yang Ning-I NI Wang Chao-Yung CY Hsieh I-Chang IC Hung Ming-Jui MJ Chen Tien-Hsing TH

Diabetology & metabolic syndrome 20230526 1

<h4>Background and aims</h4>Clinical comparisons of angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) treatment in patients with HFrEF and T2DM are limited. This study evaluated the clinical outcomes and treatment benefits of SGLT2i versus ARNI treatment in patients with HFrEF and T2DM in a large real-world data set.<h4>Methods</h4>We identified 1487 patients with HFrEF and T2DM who were undergoing ARNI or SGLT2i treatment for the first time ...[more]

PMID: 37237322

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Project description:BackgroundPatients with type 2 diabetes mellitus (T2DM) are at increased risk of developing heart failure. Sodium-glucose cotransporter-2 inhibitors reduce the risk of hospitalization for heart failure (HHF) in patients with T2DM. We aimed to develop and validate a practical clinical risk score for HHF in patients with T2DM and assess whether this score can identify high-risk patients with T2DM who have the greatest reduction in risk for HHF with a sodium-glucose cotransporter-2 inhibitor.MethodsWe developed a clinical risk score for HHF in 8212 patients with T2DM in the placebo arm of SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53). Candidate variables were assessed using multivariable Cox regression, and independent clinical risk indicators achieving statistical significance of P<0.001 were included in the risk score. We externally validated the score in 8578 patients with T2DM in the placebo arm of DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58). The relative and absolute risk reductions in HHF with the sodium-glucose cotransporter-2 inhibitor dapagliflozin were assessed by baseline HHF risk.ResultsFive clinical variables were independent risk predictors of HHF: prior heart failure, history of atrial fibrillation, coronary artery disease, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio. A simple integer-based score (0-7 points) using these predictors identified a >20-fold gradient of HHF risk (P for trend <0.001) in both the derivation and validation cohorts, with C indices of 0.81 and 0.78, respectively. Although relative risk reductions with dapagliflozin were similar for patients across the risk scores (25%-34%), absolute risk reductions were greater in those at higher baseline risk (1-sided P for trend=0.04), with high-risk (2 points) and very-high-risk (≥3 points) patients having 1.5% and 2.7% absolute reductions in Kaplan-Meier estimates of HHF risk at 4 years, respectively.ConclusionsRisk stratification using a novel clinical risk score for HHF in patients with T2DM identifies patients at higher risk for HHF who derive greater absolute benefit from sodium-glucose cotransporter-2 inhibition.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifiers: NCT01107886 and NCT01730534.

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.

Dataset Information

Comparing angiotensin receptor-neprilysin inhibitors with sodium-glucose cotransporter 2 inhibitors for heart failure with diabetes mellitus.

Background and aims

Methods

Results

Conclusions

Publications

Comparing angiotensin receptor-neprilysin inhibitors with sodium-glucose cotransporter 2 inhibitors for heart failure with diabetes mellitus.

Similar Datasets

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