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Pearl Toh, 12 Sep 2020
Early initiation of rhythm-control therapy led to a significantly reduced risk of major adverse cardiovascular (CV) outcomes compared with usual care (typically rate control) in patients with newly diagnosed atrial fibrillation (AF) at risk of stroke, reveals the EAST-AFNET 4* trial presented at ESC 2020.

EMPEROR-Reduced: Empagliflozin cuts CV death/HHF and renal events in HFrEF

03 Sep 2020
Dr Milton Packer

Empagliflozin significantly reduces cardiovascular (CV) death or hospitalization for heart failure (HHF), as well as renal events, vs placebo in patients with HF with reduced ejection fraction (HFrEF) with or without diabetes mellitus (DM), according to results of the EMPEROR-Reduced trial presented at the European Society of Cardiology (ESC) Congress 2020.

In the trial (n=3,730), in which 73 percent of patients had left ventricular ejection fraction (LVEF) ≤30 percent and 79 percent had N-terminal pro-brain natriuretic peptide (NT-proBNP) level ≥1,000 pg/mL at baseline, the composite primary endpoint of CV death or HHF was significantly reduced by 25 percent in patients randomized to receive empagliflozin 10 mg QD vs those receiving placebo (15.8 vs 21 per 100 patient-years; hazard ratio [HR], 0.75; 95 percent confidence interval [CI], 0.65 to 0.86; p<0.0001), after a median follow-up of 16 months. [Packer M, et al, ESC 2020; N Engl J Med 2020, doi: 10.1056/NEJMoa2022190]   

“Empagliflozin’s benefit in the primary endpoint was driven by a 31 percent risk reduction in first HHF vs placebo [10.7 vs 15.5 per 100 patient-years; HR, 0.69; 95 percent CI, 0.59 to 0.81],” said investigator Dr Milton Packer of the Baylor University Medical Center, Dallax, Texas, US. The rate of CV death was 7.6 vs 8.1 per 100 patient-years for empagliflozin vs placebo (HR, 0.92; 95 percent CI, 0.75 to 1.12).

The number of patients needed to be treated with empagliflozin to prevent one primary endpoint event was 19.

“The benefit of empagliflozin on the primary endpoint was consistent in 12 prespecified subgroups,” said Packer.

Of note, the magnitude of benefit was similar between patients with DM (HR, 0.72; 95 percent CI, 0.60 to 0.87) and those without DM (HR, 0.78; 95 percent CI, 0.64 to 0.97) at baseline. A significant benefit was also observed both in patients who used an angiotensin receptor-neprilysin inhibitor (ARNI) (HR, 0.64; 95 percent CI, 0.45 to 0.89) and those who did not (HR, 0.77; 95 percent CI, 0.66 to 0.90).

In terms of secondary endpoints, total (first and recurrent) HHF were reduced by 30 percent with empagliflozin vs placebo (HR, 0.70; 95 percent CI, 0.58 to 0.85; p=0.0003). The annual decline in estimated glomerular filtration rate (eGFR) was significantly slower in the empagliflozin vs placebo group (difference in eGFR slope, +1.73 mL/min/1.73 m2/year; p<0.001) during the double-blind treatment period.

The risk of the composite renal endpoint (chronic dialysis, renal transplantation or sustained reduction of eGFR) was likewise reduced, by 50 percent, with empagliflozin vs placebo (1.6 vs 3.1 per 100 patient-years; HR, 0.50; 95 percent CI, 0.32 to 0.77).

“Empagliflozin was well tolerated in the trial,” said Packer. “Serious adverse events [AEs] occurred in 41.4 percent of patients on empagliflozin vs 48.1 percent of those on placebo, with 26.8 percent vs 34 percent of events being related to cardiac disorder and 3.2 percent vs 5.1 percent being related to worsening of renal function. No significant differences were seen in rates of volume depletion, hypotension and hypoglycaemia between the two groups.”

“EMPEROR-Reduced was conducted in a sicker population of patients with lower LVEF, higher NT-proBNP level and poorer renal function than patients in the DAPA-HF trial,” highlighted Packer.

At EMPEROR-Reduced baseline, mean LVEF was 27.2–27.7 percent, median NT-proBNP level was 1,887–1,926 pg/mL, and mean eGFR was 61.8–62.2 mL/min/1.73 m2. Almost 20 percent of patients were receiving an ARNI, while about half had DM. “At DAPA-HF baseline, patients’ LVEF was 31.2 percent, NT-proBNP level was 1,428 pg/mL, and eGFR was 66 mL/min/1.73 m2. About 10 percent of patients were on an ARNI, while 41.8 percent had DM,” he noted.

“The 25 percent risk reduction in the primary endpoint of EMPEROR-Reduced was identical to that seen in DAPA-HF. Taken together, we believe that the concordant results of EMPEROR-Reduced and DAPA-HF should be sufficient to establish SGLT-2 inhibitors as a new standard of care for patients with HFrEF,” he concluded.

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Most Read Articles
Pearl Toh, 12 Sep 2020
Early initiation of rhythm-control therapy led to a significantly reduced risk of major adverse cardiovascular (CV) outcomes compared with usual care (typically rate control) in patients with newly diagnosed atrial fibrillation (AF) at risk of stroke, reveals the EAST-AFNET 4* trial presented at ESC 2020.