Empagliflozin beneficial in HFrEF regardless of existing treatment
medwireNews: Empagliflozin decreases the risk for serious outcomes in people with heart failure with reduced ejection fraction (HFrEF) irrespective of which medications they were already taking and at what intensity, suggests a post-hoc EMPEROR-Reduced analysis.
At enrollment, 88.3% of the 3730 trial participants were taking an angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor blocker (ARB), or angiotensin receptor neprilysin inhibitor (ARNI). In addition, 94.7% were taking a beta blocker and 71.3% a mineralocorticoid receptor antagonist (MRA).
However, Subodh Verma (University of Toronto, Ontario, Canada) and co-researchers found that the proportion of people receiving at least 50% of the full target dose of these medications varied from less than half for ACE inhibitors and ARBs to almost all for MRAs.
The team grouped the study participants by background medication class and whether or not they were receiving at least 50% of the target dose.
This revealed that participants derived a similar size of benefit from being given empagliflozin versus placebo regardless of the dose of background medication received, and this was true for all classes of background medication and for dual and triple combinations of background medication classes.
And this was also generally consistent for the primary endpoint of hospitalization for HF or cardiovascular death, for the extended endpoint including urgent HF visits requiring intravenous therapy and outpatient intensification of oral diuretic therapy, and for total HF hospitalizations.
In a commentary accompanying the publication in The Lancet Diabetes & Endocrinology, Lars Rydén and Giulia Ferrannini, both from the Karolinska Institute in Stockholm, Sweden, say that these findings are in line with previous results obtained with dapagliflozin in DAPA-HF, although they also advise caution, given the limitations of post-hoc analyses.
They also raise the issue the designs of such trials, which do not allow researchers to explore the possibility that a new medication class such as sodium-glucose cotransporter (SGLT)2 inhibitors might be superior to established treatments.
“Exploring this possibility would require a different study outline, in which the other drugs are each in turn exchanged for the SGLT2 inhibitor,” say the commentators.
They conclude: “For the time being, the analyses by Verma and colleagues are reassuring, allowing the institution of novel therapy with the knowledge that it works with different combinations and doses of traditional heart failure treatment.”
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