Empagliflozin HF benefits extend across spectrum of kidney disease
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Key takeaways:
- Empagliflozin is beneficial in patients with HF and all stages of chronic kidney disease.
- The SGLT2 inhibitor should be used “early in the disease process” to reduce cardiorenal risk.
Kidney disease does not influence the benefits of the SGLT2 inhibitor empagliflozin on major HF events, even in patients at high renal risk, according to a new analysis of the EMPEROR-Pooled study.
“In indicated patients, SGLT2 inhibitors should be used early in the disease process to modify cardiorenal risk and improve long-term outcomes,” Healio | Cardiology Today Editorial Board Member Javed Butler, MD, MPH, MBA, FACC, FAHA, FESC, president of the Baylor Scott and White Research Institute, senior vice president for Baylor Scott and White Health and distinguished professor of medicine at the University of Mississippi, told Healio. “This can be done wherever the patient has a touch point, whether in primary care or cardiology or endocrinology or nephrology.”
Benefit regardless of CKD stage
Butler and colleagues analyzed data from 9,718 participants from the EMPEROR-Pooled analysis using combined individual patient data from the EMPEROR-Reduced and EMPEROR-Preserved trials (mean age, 70 years; 63% men). EMPEROR-Preserved was conducted from March 27, 2017, to April 26, 2021; EMPEROR-Reduced was conducted from April 6, 2017, to May 28, 2020. For this post hoc analysis, the researchers stratified participants by Kidney Disease Improving Global Outcomes (KDIGO) categories, based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Categories were defined as low-, moderate-, high-, and very high-risk categories, comprising 32%, 29.1%, 21.9% and 17% of the participants, respectively.
The findings were published in the Journal of the American College of Cardiology.
In the placebo arm, when compared with lower-risk categories, participants at higher risk experienced a slower rate of decline in eGFR, but a higher risk for a composite kidney event.
Empagliflozin reduced risk for CV death or HF hospitalizations similarly across all KDIGO categories, with HRs of 0.81 for low-risk participants (95% CI, 0.66-1.01), 0.63 for moderate-risk participants (95% CI, 0.52-0.76), 0.82 for high-risk participants (95% CI, 0.68-0.98) and 0.84 for very high-risk participants (95% CI, 0.71-1.01; P for trend = .3). “Empagliflozin reduced the rate of decline in eGFR whether it was estimated by chronic slope, total slope, or unconfounded slope,” the researchers wrote.
When compared with the unconfounded slope, the magnitude of the effect on chronic slope was larger, and the effect on total slope was smaller.
In EMPEROR-Reduced, participants at lowest risk experienced the largest effect of empagliflozin on eGFR slope; however, researchers did not observe this effect among participants in EMPEROR-Preserved.
“There are several important messages here,” Butler told Healio. “First, while not the focus of this study, it is important to realize how easy it is to assess UACR on spot urine and how potent this test is to risk stratify for cardiorenal outcomes. Hence, more frequent assessment should be considered in the primary care and cardiology practices. Second, using eGFR and UACR, one can risk stratify patients with HF with reduced or preserved EF for both CV and kidney risk. Third, SGLT2 inhibitors benefit patients across the spectrum of risk profile. Lastly, we need to come together as a clinical and research community with a consensus as to how we will assess kidney function deterioration or benefit of intervention using UACR and eGFR slopes, in terms of definitions and thresholds.”
Butler said more work is needed to better understand the safety and benefit of SGLT2 inhibitors in people with type 1 diabetes and lower-risk type 2 diabetes, as well as post-MI and dialysis patients.
SGLT2 inhibitor use encouraged even in severe CKD
In a related editorial, Søren L. Kristensen, MD, PhD, of the department of cardiology at Copenhagen University Hospital, Denmark, and colleagues wrote that Butler and colleagues’ findings, together with data from EMPA-Kidney, demonstrate the safety of SGLT2 inhibitors in lower eGFR settings and encourages their use, even in severe chronic kidney disease (CKD).
“It has been proposed recently as a treatment for patients on chronic dialysis, with type 1 diabetes, and for cardiovascular disease, large post-myocardial infarction trials are ongoing, and it may be further speculated that SGLT2 inhibition should be evaluated in more rare conditions like pulmonary arterial hypertension and in patients with a heart transplant,” Kristensen and colleagues wrote. “It is difficult not be enthusiastic about the use and consistent benefits of SGLT2 inhibitors, and the study by Butler and colleagues adds to our understanding and informs decision-making when we treat patients with HF and CKD.”
Reference:
For more information:
Javed Butler, MD, MPH, MBA, FACC, FAHA, FESC, can be reached at javed.butler@bswhealth.org.
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