Benefits of dapagliflozin consistent in CKD, regardless of concomitant CVD
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The benefits of dapagliflozin remain consistent in patients with chronic kidney disease, with and without type 2 diabetes, independent of baseline CV status, according to an analysis of the DAPA-CKD trial.
As Healio previously reported, treatment with the SGLT2 inhibitor dapagliflozin (Farxiga, AstraZeneca) 10 mg per day reduced risk for worsening renal function and death due to CVD or renal disease compared with placebo in patients with CKD, with and without type 2 diabetes.
During the virtual American Heart Association Scientific Sessions, John J.V. McMurray, MD, professor of cardiology at the Institute of Cardiovascular and Medical Sciences at University of Glasgow in Scotland, reported results of a prespecified subgroup analysis of patients in primary and secondary prevention subgroups based on history of CVD. At baseline, 38% of patients assigned dapagliflozin and 37% assigned placebo had CVD, including MI, stroke, atrial fibrillation/flutter or HF.
The primary outcome was estimated glomerular filtration rate (eGFR) decline of 50% or more, end-stage kidney disease, or CV or kidney death. Secondary outcomes included a composite of eGFR decline of 50% or more, end-stage kidney disease or kidney death; CV death or HF; and all-cause mortality.
Researchers found that, regardless of baseline CV status, dapagliflozin showed similar risk reduction for the primary endpoint at 32 months (HR without CVD = 0.61; 95% CI, 0.48-0.79; vs. HR with CVD = 0.61; 95% CI, 0.47-0.79; P for interaction = .9).
These findings were also consistent for all secondary outcomes, including eGFR decline of 50% or more, end-stage kidney disease or kidney death (HR without CVD = 0.61; 95% CI, 0.47-0.79; vs. HR with CVD = 0.49; 95% CI, 0.34-0.69; P for interaction = .29); CV death or HF (HR without CVD = 0.67; 95% CI, 0.4-1.13; vs. HR with CVD = 0.7; 95% CI, 0.52-0.94; P for interaction = .88); and all-cause mortality (HR without CVD = 0.63; 95% CI, 0.41-0.98; vs. HR with CVD = 0.7; 95% CI, 0.51-0.95; P for interaction = .71).
In an exploratory analysis of CV outcomes, investigators observed comparable results among patients with and without baseline CVD:
- CV death, MI or stroke (HR without CVD = 0.83; 95% CI, 0.55-1.25; vs. HR with CVD = 0.94; 95% CI, 0.71-1.26; P for interaction = .61);
- first HF hospitalization (HR without CVD = 0.31; 95% CI, 0.1-0.94; vs. HR with CVD = 0.54; 95% CI, 0.35-0.82; P for interaction = .35);
- CV death, MI, stroke or HF hospitalization (HR without CVD = 0.73; 95% CI, 0.5-1.08; vs. HR with CVD = 0.8; 95% CI, 0.62-1.03; P for interaction = .72); and
- all-cause mortality, MI, stroke, HF hospitalization or end-stage kidney disease (HR without CVD = 0.68; 95% CI, 0.54-0.85; vs. HR with CVD = 0.72; 95% CI, 0.56-0.89; P for interaction = .77).
The results were simultaneously published in Circulation.
“Patients with chronic kidney disease who also have CVD are at the highest risk of all — and that risk is for two of the worst things you can imagine — HF and kidney failure (no one wants to be on dialysis), as well as an extremely high risk for death — and dapagliflozin reduces the risk of each of these outcomes, so there is a very large clinical benefit and that benefit begins early after starting treatment,” McMurray told Healio. “Many cardiology patients also have chronic kidney disease and this is an important new treatment for these individuals.”
Reference:
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McMurray JJV, et al. FS.02 - SGLT2i for nondiabetic 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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