Ertugliflozin HF benefits differ based on kidney disease severity
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The HF benefits observed in adults with type 2 diabetes and atherosclerotic CVD treated with the SGLT2 inhibitor ertugliflozin were greater among those with moderate to high risk for kidney disease.
In exploratory analyses of the VERTIS-CV trial, the effect of ertugliflozin (Steglatro, Merck) on hospitalization for HF and a composite endpoint of hospitalization for HF and CV death differed based on the severity of kidney disease parameters that included urinary to albumin creatinine ratio and estimated glomerular filtration rate (eGFR).
“The key message is that urine albumin is a key factor to measure in people with diabetes to stratify risk for the heart and kidney,” David Cherney, MD, PhD, FRCPC, professor of medicine in the division of nephrology, University Health Network, University of Toronto, told Healio. “A related message is the importance for cardio-kidney-endo integration of care to best help our patients.”
Importance of albuminuria
The presence of albuminuria is an important risk factor for the development of CVD, including HF, yet patients with type 2 diabetes are rarely risk stratified by renal parameters in many cardiology practices, Cherney said at the virtual American Heart Association Scientific Sessions.
As Healio previously reported, initial results of VERTIS-CV, presented at the American Diabetes Association Scientific Sessions in June, demonstrated that adults with type 2 diabetes and established ASCVD were not more likely to experience a CV event during 3.5 years of follow-up with ertugliflozin compared with placebo. The randomized controlled trial included more than 8,200 participants from 34 countries.
In prespecified exploratory analyses of VERTIS-CV, researchers assessed the effect of ertugliflozin on CV events by baseline levels of eGFR (CKD stage 1, 2 or 3), baseline urinary albumin to creatinine ratio (normal or elevated) and by baseline Kidney Disease Improving Global Outcomes CKD risk category (KDIGO CKD; low, moderate or high/very high risk). Analyses included testing of treatment group-by-subgroup interactions without adjustment for multiple testing. The findings were simultaneously published in Circulation.
The proportions of participants with CKD stages 1, 2, and 3 at baseline were 25%, 53% and 22%, respectively, whereas 60% and 40% of participants had normal and elevated albuminuria, respectively. Within the cohort, 49%, 32% and 19% were classified into the KDIGO CKD low-, moderate-, and high-/very high-risk categories, respectively.
Among participants with CKD stage 3 vs. placebo, researchers observed significant risk reduction for time to first hospitalization for HF (HR = 0.5; 95% CI, 0.33-0.76) and the composite of hospitalization for HF and CV death (HR = 0.76; 95% CI, 0.59-0.995).
Researchers observed a similar benefit among participants with elevated urinary albumin-to-creatinine ratio for both hospitalization for HF (HR = 0.55; 95% CI, 0.4-0.75) and the composite HF and CV death endpoint (HR = 0.73; 95% CI, 0.6-0.89).
There was also a similar benefit among participants in the KDIGO CKD moderate- and high-/very high-risk categories, with the highest absolute event rate reductions in these subgroups, Cherney said.
Predicting therapy response
Cherney cautioned that due to small sample sizes and low numbers of events in some subgroups, interpretability of results for these subgroups is limited; the assessment of within-subgroup statistical significance was not the aim of the analyses.
“Further exploration of the association between CVD, CKD, and SGLT2 inhibition is warranted in dedicated kidney disease cohorts,” the researchers wrote.
In Circulation the authors noted that the findings highlight the potential value of stratifying kidney disease risk by both urinary albumin to creatine ratio and measures of kidney function in patients with type 2 diabetes to predict both CV risk and response to ertugliflozin.
“A take-home for me, as a cardiologist, is that we need to measure urine albumin to risk-stratify patients,” Christopher P. Cannon, MD, cardiologist at Brigham and Women’s Hospital, professor of medicine at Harvard Medical School and a co-investigator with VERTIS-CV, told Healio. “It is a potent way to identify patients at increased risk, as well as those who would derive the greatest benefit from SGLT2 inhibitors. I have never ordered urine albumin, so I need to start.”
Reference:
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Cherney D. SGLT2i for non-diabetic indications: Updates from mega-trials and mechanistic insights. Presented at: American Heart Association Scientific Sessions; Nov. 13-17, 2020 (virtual meeting).
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