Elevated pulmonary artery diastolic pressure is “perhaps the best predictor of bad outcomes in patients with heart failure, including hospitalization and death,” and new evidence clearly showed that the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin cuts this metric in patients by a clinically significant amount,, said at the virtual annual scientific meeting of the Heart Failure Society of America.
The evidence he collected from a total of 65 heart failure patients with either reduced or preserved ejection fraction is the first documentation from a randomized, controlled study to show a direct effect by a SGLT2 inhibitor on pulmonary artery (PA) pressures.
Other key findings were that the drop in PA diastolic pressure with empagliflozin treatment compared with placebo became discernible early (within the first 4 weeks on treatment), that the pressure-lowering effect steadily grew over time, and that it showed no link to the intensity of loop diuretic treatment, which held steady during 12 weeks on treatment and 13 weeks of overall monitoring.
The study’s primary endpoint was the change from baseline in PA diastolic pressure after 12 weeks on treatment. The 31 patients who completed the full 12-week course had an average drop in their PA diastolic pressure of about 1.5 mm Hg, compared with 28 patients who completed 12 weeks on placebo. Average PA diastolic pressure at baseline was about 21 mm Hg in both treatment arms, and on treatment this fell by more than 0.5 mm Hg among those who received empagliflozin and rose by close to 1 mm Hg among control patients.
“There appears to be a direct effect of empagliflozin on pulmonary artery pressure that’s not been previously demonstrated” by an SGLT2 inhibitor, Dr. Kosiborod said. “I think this is one mechanism of action” for this drug class. “If you control pulmonary artery filling pressures you can prevent hospitalizations and deaths.”
Small reductions matter
“Small pressure differences are particularly important for pulmonary hypertension,” commented, professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn., and the report’s designated discussant.
“In the Vanderbilt heart failure database, patients with a pulmonary artery mean pressure of 20-24 mm Hg had 30% higher mortality than patients with lower pressures,” Dr. Stevenson noted. “This has led to a new definition of pulmonary hypertension, a mean pulmonary artery pressure above at or above 20 mm Hg.”
In Dr. Kosiborod’s study, patients began with an average PA mean pressure of about 30 mm Hg, and empagliflozin treatment led to a reduction in this metric with about the same magnitude as its effect on PA diastolic pressure. Empagliflozin also produced a similar reduction in average PA systolic pressure.
“We can expect a reduction in pulmonary hypertension to help protect against right-heart congestion, which then protects against right heart failure” and prevents right failure from triggering or worsening left ventricular failure, Dr. Stevenson explained.
© Frontline Medical Communications 2018-2021. Reprinted with permission, all rights reserved.