AF, PAD, diabetes prevention data reported from DAPA-CKD
medwireNews: The latest DAPA-CKD data show the large absolute benefits of dapagliflozin treatment in people with peripheral artery disease (PAD) or atrial fibrillation (AF), and that the medication may reduce the risk for type 2 diabetes in people with initial prediabetes.
A dedicated session at the virtual 57th EASD Annual Meeting gave the DAPA-CKD researchers the opportunity to bring conference delegates up to speed on recent and new data from the landmark trial.
John McMurray (University of Glasgow, UK) rounded up the cardiovascular findings, including unpublished data showing particularly large absolute risk reductions in people with PAD or AF, in addition to chronic kidney disease, given dapagliflozin versus placebo.
Patients with PAD had a markedly higher rate of the trial’s primary endpoint (estimated glomerular filtration rate [eGFR] decrease ≥50%, end-stage renal disease, or cardiorenal death) than those without, at 10.9 versus 7.1 per 100 person–years for those taking placebo. But the corresponding rates for those taking dapagliflozin were 7.7 and 4.4 per 100 person–years, and the size of the risk reduction did not significantly differ according to the presence or absence of PAD.
The same was true for the secondary endpoint of cardiovascular death or heart failure hospitalization.
There was a similar pattern for AF, but in this case the difference in the secondary cardiovascular endpoint was particularly striking. This occurred at rates of 14.9 versus just 2.5 per 100 person–years for people with versus without AF in the placebo group, and at 6.4 versus 1.9 per 100 person–years in the dapagliflozin group.
The dapagliflozin-associated risk reductions were 57% for people with AF and 22% for those without, producing a borderline significant p value for interaction of 0.07, indicating “a suggestion, perhaps, that there is a particularly powerful benefit of dapagliflozin” in reducing cardiovascular risk in people with existing AF, said McMurray.
The presenter noted that there are no existing recommendations on screening for AF, “but I think more and more of us in practice are appreciating that certainly a yearly ECG [electrocardiogram] is probably worthwhile in our patients because there’s a relatively high risk of developing atrial fibrillation, especially in older patients over the age of 60.”
He added: “It is such an important – and treatable – cardiovascular problem that the relatively small expense of regular ECG screening is well worthwhile.”
McMurray also reiterated the high risk for poor outcomes, particularly cardiovascular events, in people with heart failure at baseline, and that dapagliflozin reduced risk in both those with and without this condition.
In the same session, Silvio Inzucchi (Yale School of Medicine, New Haven, Connecticut, USA) revealed the results of a combined analysis of people in DAPA-HF and DAPA-CKD. Approximately 55% and 33% of people in the former and latter study, respectively, did not have diabetes at baseline, totaling around 4000 people.
During follow-up, 5.3% of these people developed type 2 diabetes, almost all of whom had prediabetes at baseline. Use of dapagliflozin rather than placebo was associated with a significant 33% reduction in risk for progression to type 2 diabetes.
This “may be considered an additional benefit of this medication” in people given dapagliflozin for renal disease, said Inzucchi.
He noted, however, that glycated hemoglobin levels did not differ between people taking dapagliflozin and placebo, “suggesting that the effect on new-onset diabetes is not merely glycemic masking but perhaps represents a more fundamental effect on the pathogenesis of type 2 diabetes.”
In addition, David Wheeler (University College London, UK) rounded up the trial’s renal findings to date.
He reminded the audience of data showing that dapagliflozin reduced the risk for the primary endpoint versus placebo regardless of whether or not the participants had diabetes, and irrespective of the underlying cause of renal disease and its stage. The acute drop in eGFR on starting dapagliflozin was also unaffected by kidney disease stage. Dapagliflozin reduced albuminuria more than placebo, particularly in people with type 2 diabetes.
Wheeler reiterated that dapagliflozin treatment significantly reduced all-cause mortality. But given that this effect was largely driven by non-cardiovascular deaths, comprising mostly infections and malignancy, it is “not completely clear as to why this is the case,” adding that they anticipated that any effect on mortality would be driven by a reduction in cardiovascular deaths.
There were fewer acute kidney injury events with dapagliflozin versus placebo, which Wheeler described as “hugely reassuring” for doctors considering whether to prescribe dapagliflozin to patients with lower eGFRs.
Discussing such patients, he noted that many in DAPA-CKD continued on dapagliflozin down to eGFRs of 15 mL/min per 1.73 m2 and even lower without any safety signals emerging.
Wheeler said: “We don’t know how low we can go, but there doesn’t seem to be a negative side of continuing this drug down at these lower levels of eGFR and we may well be benefiting these patients and we don’t seem to be putting them at risk.”
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